The present invention relates to calving characteristics in bovine subjects. In particular, the invention relates to genetic markers for the determination of calving characteristics in a bovine subject and a diagnostic kit for detection of genetic marker(s) associated with calving characteristics.
Stillbirth, calving difficulty and calf size at birth are economic important calving traits, which are included in the Danish dairy cattle breeding program (Pedersen et al., 2003). The incidence of stillbirths for Holstein cattle has increased in several Holstein populations during the last two decades (Hansen et al., 2004). The increased incidence of stillbirths reduces the potential number of replacement heifers in dairy cattle herds and is associated with ethical problems.
Both direct and maternal genetic components are associated with the calving traits. In Danish Holstein, the heritability (h2) estimates of the calving traits, measured as a direct sire effect (h2=0.05-0.19) are higher than the heritability estimates of the calving traits measured as a maternal grand sire effect (h2=0.04-0.06). The genetic correlation between calving traits measured as a direct sire effect (0.69-0.93) are markedly higher than the genetic correlation between calving traits measured as a maternal grand sire effect (0.01-0.62). The genetic component associated with the calving traits may be due to the segregation of one or more quantitative trait loci (QTL).
Quantitative trait locus (QTL) is a region of DNA that is associated with a particular trait (e.g. a disease or calving characteristics). A QTL is not necessarily a gene itself, but rather a DNA region that is closely linked to the genes that underlie the trait in question. Most likely, a QTL is a set of genes that collectively encode a quantitative trait that varies continuously across a population. Thus, the allelic variation of the QTL is associated with variation in a quantitative trait. The presence of QTL is inferred from genetic mapping, in which the genetic location of the QTL is determined relative to known genetic markers.
The identification of genetic markers that are linked to a particular phenotype, such as calving traits or to a heritable disease, has been facilitated by the discovery of microsatellite markers as a source of polymorphic markers and single nucleotide polymorphisms linked to a mutation causing a specific phenotype. Markers linked to the mutation or the mutation itself causing a specific phenotype of interest are localised by use of genetic analysis in pedigrees and also by exploiting linkage disequilibrium (LD) when looking at populations
Linkage disequilibrium reflects recombination events dating back in history and the use of LD mapping within families increases the resolution of mapping. LD exists when observed haplotypes in a population do not agree with the haplotype frequencies predicted by multiplying together the frequency of individual genetic markers in each haplotype. In this respect the term haplotype means a set of closely linked genetic markers present on one chromosome which tend to be inherited together.
In order for LD mapping to be efficient the density of genetic markers needs to be compatible with the distance across which LD extends in the given population. In a study of LD in dairy cattle population using a high number of genetic markers (284 autosomal microsatellite markers) it was demonstrated that LD extends over several tens of centimorgans for intrachromosomal markers (Farnir et al. 2000). Similarly, Georges, M (2000) reported that the location of a genetic marker that is linked to a particular phenotype in livestock typically has a confidence interval of 20-30 cM (corresponding to maybe 500-1000 genes) (Georges, M., 2000). The existence of linkage disequilibrium is taken into account in order to use maps of particular regions of interest with high confidence.
Several QTL have been detected for calving traits in other Holstein populations (e.g. Kühn et al., 2003; Schrooten et al., 2000; Elo et al., 1999). Some QTL may affect more than one trait, and some QTL may even be located at the same chromosomal position for different traits. If the QTL affects multiple traits then it is important, for e.g. selection purposes, to test if it is a pleiotropic or linked QTL affecting the traits.
Calving traits such as stillbirth, calving difficulty and calf size are not easily predicted. The use of genetic analysis and genetic selection appears to be a possible method for prognostication of these calving traits. Once mapped, a QTL can be usefully applied in marker assisted selection.
It is an object of the present invention to provide an application method for marker assisted selection of polymorphisms in the bovine genome, wherein polymorphisms are associated with calving trait characteristics, such as still birth, calving difficulties, and calf size; and/or provide genetic markers for use in such a method, and/or to provide animals selected using the method of the invention.
One aspect of the present invention relates to a method of determining calving characteristics in a bovine subject, comprising detecting in a sample from said bovine subject the presence or absence of at least one genetic marker that is linked to at least one trait indicative of increased risk of stillbirth and/or increased risk of calving difficulties and/or increased risk of non-desired calf size, wherein said at least one genetic marker is located on the bovine chromosome BTA3 in a region flanked by and including polymorphic microsatellite markers INRA006 and BM7225 and/or
A second aspect of the present invention relates to diagnostic kit for use in detecting the presence in a bovine subject of at least one genetic marker associated with bovine calving characteristics, comprising at least one oligonucleotide sequence, wherein the nucleotide sequences are selected from any of SEQ ID NO.: 1 to SEQ ID NO.: 558 and/or any combination thereof.
The present invention relates to genetic determinants of calving characteristics in dairy cattle. Calving traits, such as calving difficulties, stillbirths and calf size are economically important factors in the dairy industry. Therefore, it is of economic interest to identity those bovine subjects that have a genetic predisposition for specific calving characteristics. Bovine subjects with genetic predisposition for calving characteristics are carriers of non-desired traits, which both complicate calving, and can be passed on to their offspring.
The term “bovine subject” refers to cattle of any breed and is meant to include both cows and bulls, whether adult or newborn animals. No particular age of the animals are denoted by this term. One example of a bovine subject is a member of the Holstein breed. In one embodiment, the bovine subject is a member of the Holstein-Friesian cattle population. In another embodiment, the bovine subject is a member of the Holstein Swartbont cattle population. In another embodiment, the bovine subject is a member of the Deutsche Holstein Schwarzbunt cattle population. In another embodiment, the bovine subject is a member of the US Holstein cattle population. In one embodiment, the bovine subject is a member of the Red and White Holstein breed. In another embodiment, the bovine subject is a member of the Deutsche Holstein Schwarzbunt cattle population. In one embodiment, the bovine subject is a member of any family, which include members of the Holstein breed. In one embodiment the bovine subject is a member of the Danish Red population. In another embodiment the bovine subject is a member of the Finnish Ayrshire population. In yet another embodiment the bovine subject is a member of the Swedish Red population. In a further embodiment the bovine subject is a member of the Danish Holstein population. In another embodiment, the bovine subject is a member of the Swedish Red and White population. In yet another embodiment, the bovine subject is a member of the Nordic Red population.
In one embodiment of the present invention, the bovine subject is selected from the group consisting of Swedish Red and White, Danish Red, Finnish Ayrshire, Holstein-Friesian, Danish Holstein and Nordic Red. In another embodiment of the present invention, the bovine subject is selected from the group consisting of Finnish Ayrshire and Swedish Red cattle. In another embodiment of the present invention, the bovine subject is selected from the group consisting of Finnish Ayrshire and Swedish Red cattle.
In one embodiment, the bovine subject is selected from the group of breeds shown in table 1a
In one embodiment, the bovine subject is a member of a breed selected from the group of breeds shown in table 1b
In one embodiment, the bovine subject is a member of a breed selected from the group of breeds shown in table 1c
The term “genetic marker” refers to a variable nucleotide sequence (polymorphism) of the DNA on the bovine chromosome. The variable nucleotide sequence can be identified by methods known to a person skilled in the art, for example by using specific oligonucleotides in for example amplification methods and/or hybridization techniques and/or observation of a size difference. However, the variable nucleotide sequence may also be detected by sequencing or for example restriction fragment length polymorphism analysis. The variable nucleotide sequence may be represented by a deletion, an insertion, repeats, and/or a point mutation. Thus, a genetic marker comprises a variable number of polymorphic alleles.
One type of genetic marker is a microsatellite marker that is linked to a quantitative trait locus. Microsatellite markers refer to short sequences repeated after each other. In short sequences are for example one nucleotide, such as two nucleotides, for example three nucleotides, such as four nucleotides, for example five nucleotides, such as six nucleotides, for example seven nucleotides, such as eight nucleotides, for example nine nucleotides, such as ten nucleotides. However, changes sometimes occur and the number of repeats may increase or decrease. The specific definition and locus of the polymorphic microsatellite markers can be found in the USDA genetic map (Kappes et al. 1997; or by following the link to U.S. Meat Animal Research Center http://www.marc.usda.gov/).
In one embodiment of the present invention, specific marker alleles are linked to quantitative trait loci affecting calving characteristics.
It is furthermore appreciated that the nucleotide sequences of the genetic markers of the present invention are genetically linked to traits for calving in a bovine subject. Consequently, it is also understood that a number of genetic markers may be generated from the nucleotide sequence of the DNA region(s) flanked by and including the genetic markers according to the method of the present invention.
Calving in a bovine subject is affected by a number of characteristics. Traits that affect calving according to the present invention are for example the occurrence of stillbirth (SB), calving difficulty (CD) and the size of the calf at birth (CS). The traits are assessed by a direct effect (D) of the sire in the calf. However, the traits are also assessed as a maternal effect (M) of the sire in the mother of the calf.
By the term calving characteristics is meant traits which affect calving in the bovine subject or its off-spring. Thus, calving characteristics of a bull are physically manifested by its off-spring—both female and male.
In the present invention calving characteristics comprise the traits SB, CD, and CS, which refer to the following characteristics:
SB: Designates stillbirths.
CS: Size of calves.
CD: Calving difficulties, which are based on registrations from the farmers where it is subjectively registered how difficult the calving is. The calving difficulties consist of four categories:
In one embodiment of the present invention, the method and kit described herein relates to still births, calving difficulties as categorized herein and/or calf size. In one embodiment of the present invention, the method and kit described herein relates to still births. In another embodiment, the method and kit of the present invention pertains to calving difficulties, such as detected by the calving difficulty categories described above. In yet another embodiment, the method and kit of the present invention relates to calf size. In another embodiment of the present invention, the method and kit described herein relates to any combination of still birth, calving difficulties and/or calf size.
The granddaughter design includes analysing data from DNA-based markers for grandsires that have been used extensively in breeding and for sons of grandsires where the sons have produced offspring. The phenotypic data that are to be used together with the DNA-marker data are derived from the daughters of the sons. Such phenotypic data could be for example milk production features, features relating to calving, meat quality, or disease. One group of daughters has inherited one allele from their father whereas a second group of daughters has inherited the other allele from their father. By comparing data from the two groups information can be gained whether a fragment of a particular chromosome is harbouring one or more genes that affect the trait in question. It may be concluded whether a QTL is present within this fragment of the chromosome.
A prerequisite for performing a granddaughter design is the availability of detailed phenotypic data. In the present invention such data have been available (http://www.Ir.dk/kvaeq/diverse/principles.pdf).
In contrast, DNA markers can be used directly to provide information of the traits passed on from parents to one or more of their offspring when a number of DNA markers on a chromosome have been determined for one or both parents and their offspring. The markers may be used to calculate the genetic history of the chromosome linked to the DNA markers.
The frequency of recombination is the likelihood that a recombination event will occur between two genes or two markers. The frequency of recombination may be calculated as the genetic distance between the two genes or the two markers. Genetic distance is measured in units of centiMorgan (cM). One centiMorgan is equal to a 1% chance that a marker at one genetic locus will be separated from a marker at a second locus due to crossing over in a single generation. One centiMorgan is equivalent, on average, to one million base pairs.
BTA is short for Bos taurus autosome.
One aspect of the present invention relates to a method of determining calving characteristics in a bovine subject, comprising detecting in a sample from said bovine subject the presence or absence of at least one genetic marker that is linked to at least one trait indicative of increased risk of stillbirth and/or increased risk of calving difficulties and/or increased risk of non-desired calf size, wherein said at least one genetic marker is located on the bovine chromosome BTA3 in a region flanked by and including polymorphic microsatellite markers INRA006 and BM7225 and/or BTA4 in the region flanked by and including polymorphic microsatellite markers BMS1788 and MGTG4B and/or, BTA5 in the region flanked by and including polymorphic microsatellite markers BMS1095 and BM2830 and/or, BTA7 in a region flanked by and including polymorphic microsatellite markers BM7160 and BL1043 and/or, BTA8 in a region flanked by and including polymorphic microsatellite markers IDVGA-11 and BMS836 and/or, BTA9 in a region flanked by and including polymorphic microsatellite markers BMS2151 and BMS1967 and/or, BTA10 in a region flanked by and including polymorphic microsatellite markers DIK2658 and BMS2614 and/or, BTA11 in the region flanked by and including polymorphic microsatellite markers BM716 and HEL13 and/or, BTA12 in a region flanked by and including polymorphic microsatellite markers BMS410 and BMS2724 and/or, BTA15 in a region flanked by and including polymorphic microsatellite markers BR3510 and BMS429 and/or, BTA18 in a region flanked by and including polymorphic microsatellite markers IDVGA-31 and DIK4013 and/or, BTA19 in a region flanked by and including polymorphic microsatellite markers BM9202 and BMS601 and/or, BTA20 in a region flanked by and including polymorphic microsatellite markers BM3517 and UWCA26 and/or, BTA21 in a region flanked by and including polymorphic microsatellite markers DIK5182 and IDVGA-30 and/or, BTA22 in a region flanked by and including polymorphic microsatellite markers CSSM26 and BM4102 and/or, BTA24 in a region flanked by and including polymorphic microsatellite markers BMS917 and BMS3024 and/or, BTA25 in a region flanked by and including polymorphic microsatellite markers ILSTS102 and AF5 and/or, BTA26 in a region flanked by and including polymorphic microsatellite markers BMS651 and BM7237 and/or, BTA28 in a region flanked by and including polymorphic microsatellite markers, BMC6020 and BMC2208, wherein the presence of said at least one genetic marker is indicative of calving characteristics of said bovine subject and/or off-spring therefrom.
In order to determine calving characteristics in a bovine subject, wherein the at least one genetic marker is located on a bovine chromosome in the region flanked by and including the polymorphic microsatellite marker, it is appreciated that more than one genetic marker may be employed in the present invention. For example the at least one genetic marker may be a combination of at least two or more genetic markers such that the accuracy may be increased, such as at least three genetic markers, for example four genetic markers, such as at least five genetic markers, for example six genetic markers, such as at least seven genetic markers, for example eight genetic markers, such as at least nine genetic markers, for example ten genetic markers.
The at least one genetic marker may be located on at least one bovine chromosome, such as two chromosomes, for example three chromosomes, such as four chromosomes, for example five chromosomes, and/or such as six chromosomes.
In a preferred embodiment the at least one marker is selected from any of the individual markers of the tables shown herein.
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA3. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 17.1 cM to about 101.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA3. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA3 in the region flanked by and including the markers INRA006 and BM7225. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 2a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 34.6 cM to about 87.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA3. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA3 in the region flanked by and including the markers FCGR1 and HUJII77. The at least one genetic marker is selected from the group of markers shown in Table 2b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 32.5 cM to about 59.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA3. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA3 in the region flanked by and including the markers DIK4403 and INRA003. The at least one genetic marker is selected from the group of markers shown in Table 2c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 77.6 cM to about 101.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA3. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA3 in the region flanked by and including the markers DIK2702 and BM7225. The at least one genetic marker is selected from the group of markers shown in Table 2d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 52.5 cM to about 68.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA3. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA3 in the region flanked by and including the markers DIK4353 and DIK4664. The at least one genetic marker is selected from the group of markers shown in Table 2e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 59.4 cM to about 66.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA3. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA3 in the region flanked by and including the markers INRA003 and INRA123. The at least one genetic marker is selected from the group of markers shown in Table 2f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 32.5 cM to about 52.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA3. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA3 in the region flanked by and including the markers DIK4403 and DIK4353. The at least one genetic marker is selected from the group of markers shown in Table 2g:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 77.6 cM to 101.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA3. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA3 in the region flanked by and including the marker FCGR1 and HUJII77. The at least one genetic marker is selected from the group of markers shown in Table 2h:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA4. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 12.5 cM to about 112.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA4. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA4 in the region flanked by and including the markers BMS1788 and MGTG4B. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 3a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 12.5 cM to about 91.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA4. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA4 in the region flanked by and including the markers BMS1788 and BMS648. The at least one genetic marker is selected from the group of markers shown in Table 3b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 43.2 cM to about 91.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA4. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA4 in the region flanked by and including the markers BMS2646 and BMS648. The at least one genetic marker is selected from the group of markers shown in Table 3c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 43.2 cM to about 63.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA4. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA4 in the region flanked by and including the markers BMS2646 and INRA072. The at least one genetic marker is selected from the group of markers shown in Table 3d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 52.2 cM to about 73.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA4. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA4 in the region flanked by and including the markers TGLA116 and BM8233. The at least one genetic marker is selected from the group of markers shown in Table 3e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 63.0 cM to about 91.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA4. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA4 in the region flanked by and including the markers INRA072 and BMS648. The at least one genetic marker is selected from the group of markers shown in Table 3f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 63.0 cM to about 73.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA4. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA4 in the region flanked by and including the markers INRA072 and BM8233. The at least one genetic marker is selected from the group of markers shown in Table 3g:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA5. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 0.0 cM to about 116.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA5. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA5 in the region flanked by and including the markers BMS1095 and BM2830. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 4a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 0.0 cM to about 103.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA5. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA5 in the region flanked by and including the markers BMS1095 and BM315. The at least one genetic marker is selected from the group of markers shown in Table 4b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 30.1 cM to about 103.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA5. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA5 in the region flanked by and including the markers DIK2718 and BM315. The at least one genetic marker is selected from the group of markers shown in Table 4c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 30.1 cM to about 78.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA5. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA5 in the region flanked by and including the markers DIK2718 and BMS1216. The at least one genetic marker is selected from the group of markers shown in Table 4d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 18.3 cM to about 56.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA5. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA5 in the region flanked by and including the markers DIK4747 and RM500. The at least one genetic marker is selected from the group of markers shown in Table 4e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 17.3 cM to about 33.7 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA5. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA5 in the region flanked by and including the markers BP1 and DIK5002. The at least one genetic marker is selected from the group of markers shown in Table 4f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 45.5 cM to about 82.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA5. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA5 in the region flanked by and including the markers CSSM034 and DIK2943. The at least one genetic marker is selected from the group of markers shown in Table 4g:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 45.5 cM to about 66.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA5. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA5 in the region flanked by and including the markers CSSM034 and DIK5046. The at least one genetic marker is selected from the group of markers shown in Table 4h:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 66.2 cM to about 82.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA5. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA5 in the region flanked by and including the markers DIK5046 and DIK2943. The at least one genetic marker is selected from the group of markers shown in Table 4i:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 71.8 cM to about 90.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA5. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA5 in the region flanked by and including the markers ETH10 and BMS1248. The at least one genetic marker is selected from the group of markers shown in Table 4j:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA7. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 0.0 cM to about 135.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA7. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA7 in the region flanked by and including the markers BM7160 and BL1043. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 5a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 30.2 cM to about 95.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA7. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA7 in the region flanked by and including the markers DIK5412 and OARAE129. The at least one genetic marker is selected from the group of markers shown in Table 5b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 30.2 cM to about 55.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA7. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA7 in the region flanked by and including the markers DIK5412 and DIK4606. The at least one genetic marker is selected from the group of markers shown in Table 5c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 58.6 cM to about 95.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA7. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA7 in the region flanked by and including the markers UWCA20 and OARAE129. The at least one genetic marker is selected from the group of markers shown in Table 5d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 77.2 cM to about 135.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA7. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA7 in the region flanked by and including the markers BMS2258 and BL1043. The at least one genetic marker is selected from the group of markers shown in Table 5e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 77.2 cM to about 116.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA7. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA7 in the region flanked by and including the markers BMS2258 and ILSTS006. The at least one genetic marker is selected from the group of markers shown in Table 5f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 77.2 cM to about 95.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA7. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA7 in the region flanked by and including the markers BMS2258 and OARAE129. The at least one genetic marker is selected from the group of markers shown in Table 5g:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA8. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 11.3 cM to about 122.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA8. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA8 in the region flanked by and including the markers IDVGA-11 and BMS836. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 6a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 11.3 cM to about 71.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA8. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA8 in the region flanked by and including the markers IDVGA-11 and MCM64. The at least one genetic marker is selected from the group of markers shown in Table 6b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 41.6 cM to about 66.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA8. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA8 in the region flanked by and including the markers BMS678 and BMS2072. The at least one genetic marker is selected from the group of markers shown in Table 6c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 71.1 cM to about 122.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA8. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA8 in the region flanked by and including the markers MCM64 and BMS836. The at least one genetic marker is selected from the group of markers shown in Table 6d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 11.3 cM to about 41.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA8. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA8 in the region flanked by and including the markers IDVGA-11 and BMS678. The at least one genetic marker is selected from the group of markers shown in Table 6e:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA9. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 8.49 cM to about 109.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA9. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA9 in the region flanked by and including the markers BMS2151 and BMS1967. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 7a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 12.8 cM to about 90.7 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA9. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA9 in the region flanked by and including the markers ETH225 and BM4208. The at least one genetic marker is selected from the group of markers shown in Table 7b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 12.8 cM to about 64.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA9. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA9 in the region flanked by and including the markers ETH225 and BMS1290. The at least one genetic marker is selected from the group of markers shown in Table 7c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 50.0 cM to about 91.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA9. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA9 in the region flanked by and including the markers UWCA9 and BMS2819. The at least one genetic marker is selected from the group of markers shown in Table 7d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 50.0 cM to about 79.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA9. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA9 in the region flanked by and including the markers UWCA9 and BMS2753. The at least one genetic marker is selected from the group of markers shown in Table 7e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 45.7 cM to about 68.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA9. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA9 in the region flanked by and including the markers DIK5364 and DIK2816. The at least one genetic marker is selected from the group of markers shown in Table 7f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 12.8 cM to about 43.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA9. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA9 in the region flanked by and including the markers ETH225 and DIK5142. The at least one genetic marker is selected from the group of markers shown in Table 7g:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA10. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 2.7 cM to about 104.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA10. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA10 in the region flanked by and including the markers DIK2658 and BMS2614. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 8a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 9.0 cM to about 35.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA10. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA10 in the region flanked by and including the markers DIK2503 and MB077. The at least one genetic marker is selected from the group of markers shown in Table 8b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 11.0 cM to about 37.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA10. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA10 in the region flanked by and including the markers CSSM38 and DIK2000. The at least one genetic marker is selected from the group of markers shown in Table 8c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 24.0 cM to about 35.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA10. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA10 in the region flanked by and including the markers BMS528 and MB077. The at least one genetic marker is selected from the group of markers shown in Table 8d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 37.5 cM to about 80.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA10. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA10 in the region flanked by and including the markers DIK2000 and BMS1620. The at least one genetic marker is selected from the group of markers shown in Table 8e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 44.3 cM to about 74.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA10. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA10 in the region flanked by and including the markers BMS2742 and TGLA433. The at least one genetic marker is selected from the group of markers shown in Table 8f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 56.5 cM to about 74.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA10. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA10 in the region flanked by and including the markers DIK2361 and TGLA433. The at least one genetic marker is selected from the group of markers shown in Table 8g:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 74.0 cM to about 87.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA10. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA10 in the region flanked by and including the markers TGLA433 and BMS2641. The at least one genetic marker is selected from the group of markers shown in Table 8h:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 87.5 cM to about 109.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA10. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA10 in the region flanked by and including the markers BMS2641 and BMS2614. The at least one genetic marker is selected from the group of markers shown in Table 8i:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA11. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 19.4 cM to about 122.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA11. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA11 in the region flanked by and including the markers BM716 and HELL 3. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 9a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 19.4 cM to about 92.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA11. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA11 in the region flanked by and including the markers BM716 and BMS989. The at least one genetic marker is selected from the group of markers shown in Table 9b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 19.4 cM to about 50.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA11. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA11 in the region flanked by and including the markers BM716 and BM7169. The at least one genetic marker is selected from the group of markers shown in Table 9c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 30.0 cM to about 50.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA11. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA11 in the region flanked by and including the markers BM2818 and BM7169. The at least one genetic marker is selected from the group of markers shown in Table 9d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 34.8 cM to about 47.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA11. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA11 in the region flanked by and including the markers INRA177-2 and INRA131. The at least one genetic marker is selected from the group of markers shown in Table 9e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 50.3 cM to about 92.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA11. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA11 in the region flanked by and including the markers BM7169 and BMS989. The at least one genetic marker is selected from the group of markers shown in Table 9f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 61.6 cM to about 92.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA11. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA11 in the region flanked by and including the markers BM6445 and BMS989. The at least one genetic marker is selected from the group of markers shown in Table 9g:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 73.3 cM to about 92.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA11. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA11 in the region flanked by and including the markers TGLA58 and BMS989. The at least one genetic marker is selected from the group of markers shown in Table 9h:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 92.2 cM to about 109.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA1. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA11 in the region flanked by and including the markers HUJV174 and BMS460. The at least one genetic marker is selected from the group of markers shown in Table 9i:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA12. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 0.0 cM to about 109.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA12. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA12 in the region flanked by and including the markers BMS410 and BMS2724. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 10a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 50.4 cM to about 109.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA12. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA12 in the region flanked by and including the markers BM860 and BMS2724. The at least one genetic marker is selected from the group of markers shown in Table 10b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 50.4 cM to about 102.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA12. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA12 in the region flanked by and including the markers BM860 and BMS1316. The at least one genetic marker is selected from the group of markers shown in Table 10c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 63.8 cM to about 102.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA12. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA12 in the region flanked by and including the markers BMS975 and BMS1316. The at least one genetic marker is selected from the group of markers shown in Table 10d:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA15. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 9.4 cM to about 109.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA15. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA15 in the region flanked by and including the markers BR3510 and BMS429. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 11a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 48.2 cM to about 109.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA15. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA15 in the region flanked by and including the markers BMS2684 and BMS429. The at least one genetic marker is selected from the group of markers shown in Table 11b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 48.2 cM to about 91.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA15. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA15 in the region flanked by and including the markers BMS2684 and BMS2076. The at least one genetic marker is selected from the group of markers shown in Table 11c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 77.9 cM to about 109.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA15. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA15 in the region flanked by and including the markers 77.9 and 109.8. The at least one genetic marker is selected from the group of markers shown in Table 11d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 84.9 cM to about 109.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA15. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA15 in the region flanked by and including the markers BMS812 and BMS429. The at least one genetic marker is selected from the group of markers shown in Table 11e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 84.9 cM to about 94.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA15. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA15 in the region flanked by and including the markers BMS812 and BL1095. The at least one genetic marker is selected from the group of markers shown in Table 11f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 91.8 cM to about 105.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA15. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA15 in the region flanked by and including the markers BMS2076 and BMS927. The at least one genetic marker is selected from the group of markers shown in Table 11g:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 98.2 cM to about 109.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA15. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA15 in the region flanked by and including the markers BMS820 and BMS429. The at least one genetic marker is selected from the group of markers shown in Table 11 h:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 105.0 cM to about 109.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA15. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA15 in the region flanked by and including the markers BMS927 and BMS429. The at least one genetic marker is selected from the group of markers shown in Table 11i:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA18. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 0.0 cM to about 84.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers IDVGA-31 and DIK4013. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 12a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 0.0 cM to about 13.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers IDVGA-31 and BMS1322. The at least one genetic marker is selected from the group of markers shown in Table 12b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 2.9 cM to about 13.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers BMS1355 and BMS1322. The at least one genetic marker is selected from the group of markers shown in Table 12c:
In a preferred embodiment of the invention, the at least one genetic marker is located 10 in the region from about 30.2 cM to about 61.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers INRA121 and DIK4232. The at least one genetic marker is selected from the group of markers shown in Table 12d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 33.4 cM to about 54.7 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers BR4406 and ILSTS002. The at least one genetic marker is selected from the group of markers shown in Table 12e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 57.6 cM to about 84.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers BMON117 and DIK4013. The at least one genetic marker is selected from the group of markers shown in Table 12f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 61.2 cM to about 84.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers DIK4232 and DIK4013. The at least one genetic marker is selected from the group of markers shown in Table 12g:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 72.0 cM to about 76.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers BMS2785 and BM2078. The at least one genetic marker is selected from the group of markers shown in Table 12h:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 76.8 cM to about 84.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers BM2078 and DIK4013. The at least one genetic marker is selected from the group of markers shown in Table 12i:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 76.8 cM to about 78.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers BM2078 and BM6507. The at least one genetic marker is selected from the group of markers shown in Table 12j:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 78.8 cM to about 84.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA18. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA18 in the region flanked by and including the markers BM6507 and DIK4013. The at least one genetic marker is selected from the group of markers shown in Table 12k:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA19. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 0.0 cM to about 108.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA19. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA19 in the region flanked by and including the markers BM9202 and BMS601. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 13a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 0.0 cM to about 90.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA19. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA19 in the region flanked by and including the markers BM9202 and ETH3. The at least one genetic marker is selected from the group of markers shown in Table 13b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 0.0 cM to about 45.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA19. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA19 in the region flanked by and including the markers BM9202 and BP20. The at least one genetic marker is selected from the group of markers shown in Table 13c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 16.0 cM to about 45.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA19. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA19 in the region flanked by and including the markers BMS745 and BP20. The at least one genetic marker is selected from the group of markers shown in Table 13d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 47.0 cM to about 90.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA19. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA19 in the region flanked by and including the markers IDVGA-46 and ETH3. The at least one genetic marker is selected from the group of markers shown in Table 13e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 52.2 cM to about 108.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA19. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA19 in the region flanked by and including the markers BMS2389 and BMS601. The at least one genetic marker is selected from the group of markers shown in Table 13f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 69.8 cM to about 90.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA19. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA19 in the region flanked by and including the markers CSSM065 and ETH3. The at least one genetic marker is selected from the group of markers shown in Table 13g:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA20. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 0.0 cM to about 77.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA20. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA20 in the region flanked by and including the markers BM3517 and UWCA26. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 14a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 0.0 cM to about 71.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA20. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA20 in the region flanked by and including the markers BM3517 and BM5004. The at least one genetic marker is selected from the group of markers shown in Table 14b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 0.0 cM to about 26.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA20. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA20 in the region flanked by and including the markers BM3517 and BMS1754. The at least one genetic marker is selected from the group of markers shown in Table 14c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 0.6 cM to about 19.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA20. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA20 in the region flanked by and including the markers HEL12 and BMS1282. The at least one genetic marker is selected from the group of markers shown in Table 14d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 19.1 cM to about 55.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA20. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA20 in the region flanked by and including the markers BMS1282 and AGLA29. The at least one genetic marker is selected from the group of markers shown in Table 14e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 31.9 cM to about 49.7 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA20. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA20 in the region flanked by and including the markers TGLA126 and BMS2361. The at least one genetic marker is selected from the group of markers shown in Table 14f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 49.7 cM to about 55.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA20. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA20 in the region flanked by and including the markers BMS2361 and AGLA29. The at least one genetic marker is selected from the group of markers shown in Table 14g:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 55.1 cM to about 77.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA20. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA20 in the region flanked by and including the markers AGLA29 and UWCA26. The at least one genetic marker is selected from the group of markers shown in Table 14h:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 60.1 cM to about 71.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA20. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA20 in the region flanked by and including the markers BMS703 and BM5004. The at least one genetic marker is selected from the group of markers shown in Table 14i:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA21. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 5.6 cM to about 76.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA21. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA21 in the region flanked by and including the markers DIK5182 and IDVGA-30. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 15a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 11.0 cM to about 61.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA21. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA21 in the region flanked by and including the markers BMS1117 and BM846. The at least one genetic marker is selected from the group of markers shown in Table 15b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 18.3 cM to about 57.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA21. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA21 in the region flanked by and including the markers DIK2492 and DIK2913. The at least one genetic marker is selected from the group of markers shown in Table 15c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 18.3 cM to about 30.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA21. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA21 in the region flanked by and including the markers DIK2492 and DIK4001. The at least one genetic marker is selected from the group of markers shown in Table 15d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 30.9 cM to about 47.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA21. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA21 in the region flanked by and including the markers IDVGA-45 and DIK3036. The at least one genetic marker is selected from the group of markers shown in Table 15e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 33.7 cM to about 41.7 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA21. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA21 in the region flanked by and including the markers DIK2481 and BMS2815. The at least one genetic marker is selected from the group of markers shown in Table 15f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 5.5 cM to about 61.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA21. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA21 in the region flanked by and including the markers DIK5182 and BM846. The at least one genetic marker is selected from the group of markers shown in Table 15g:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA22. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 0.0 cM to about 82.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA22. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA22 in the region flanked by and including the markers CSSM26 and BM4102. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 16a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 2.9 cM to about 82.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA22. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA22 in the region flanked by and including the markers INRA026 and BM4102. The at least one genetic marker is selected from the group of markers shown in Table 16b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 2.9 cM to about 47.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA22. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA22 in the region flanked by and including the markers INRA026 and BM3628. The at least one genetic marker is selected from the group of markers shown in Table 16c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 19.1 cM to about 47.1 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA22. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA22 in the region flanked by and including the markers BM1558 and BM3628. The at least one genetic marker is selected from the group of markers shown in Table 16d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 19.1 cM to about 82.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA22. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA22 in the region flanked by and including the markers BM1558 and BM4102. The at least one genetic marker is selected from the group of markers shown in Table 16e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 47.1 cM to about 82.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA22. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA22 in the region flanked by and including the markers BM3628 and BM4102. The at least one genetic marker is selected from the group of markers shown in Table 16f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 64.1 cM to about 82.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA22. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA22 in the region flanked by and including the markers BMS875 and BM4102. The at least one genetic marker is selected from the group of markers shown in Table 16g:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA24. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 6.2 cM to about 65.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA24. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA24 in the region flanked by and including the markers BMS917 and BMS3024. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 17a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 8.2 cM to about 65.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA24. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA24 in the region flanked by and including the markers BM7151 and BMS3024. The at least one genetic marker is selected from the group of markers shown in Table 17b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 8.2 cM to about 35.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA24. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA24 in the region flanked by and including the markers BM7151 and BMS1862. The at least one genetic marker is selected from the group of markers shown in Table 17c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 11.1 cM to about 23.7 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA24. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA24 in the region flanked by and including the markers TGLA351 and BMS2270. The at least one genetic marker is selected from the group of markers shown in Table 17d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 35.5 cM to about 65.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA24. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA24 in the region flanked by and including the markers BMS1862 and BMS3024. The at least one genetic marker is selected from the group of markers shown in Table 17e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 48.8 cM to about 61.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA24. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA24 in the region flanked by and including the markers BMS466 and BMS1926. The at least one genetic marker is selected from the group of markers shown in Table 17f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 48.8 cM to about 56.3 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA24. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA24 in the region flanked by and including the markers BMS466 and INRA090. The at least one genetic marker is selected from the group of markers shown in Table 17g:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 56.3 cM to about 61.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA24. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA24 in the region flanked by and including the markers INRA090 and BMS1926. The at least one genetic marker is selected from the group of markers shown in Table 17h:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA25. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 7.2 cM to about 61.7 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA25. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA25 in the region flanked by and including the markers ILSTS102 and AF5. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 18a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 7.2 cM to about 31.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA25. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA25 in the region flanked by and including the markers ILSTS102 and BM737. The at least one genetic marker is selected from the group of markers shown in Table 18b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 7.2 cM to about 22.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA25. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA25 in the region flanked by and including the markers ILSTS102 and BMS2843. The at least one genetic marker is selected from the group of markers shown in Table 18c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 31.6 cM to about 61.7 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA25. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA25 in the region flanked by and including the markers BM737 and AF5. The at least one genetic marker is selected from the group of markers shown in Table 18d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 33.3 cM to about 46.4 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA25. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA25 in the region flanked by and including the markers ILSTS046 and BMS1353. The at least one genetic marker is selected from the group of markers shown in Table 18e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 46.4 cM to about 61.7 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA25. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA25 in the region flanked by and including the markers BMS1353 and AF5. The at least one genetic marker is selected from the group of markers shown in Table 18f:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA26. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 2.8 cM to about 66.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA26. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA26 in the region flanked by and including the markers BMS651 and BM7237. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 19a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 2.8 cM to about 60.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA26. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA26 in the region flanked by and including the markers BMS651 and BM804. The at least one genetic marker is selected from the group of markers shown in Table 19b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 2.8 cM to about 37.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA26. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA26 in the region flanked by and including the markers BMS651 and RM026. The at least one genetic marker is selected from the group of markers shown in Table 19c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 22.9 cM to about 31.7 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA26. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA26 in the region flanked by and including the markers HEL11 and BMS332. The at least one genetic marker is selected from the group of markers shown in Table 19d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 31.7 cM to about 41.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA26. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA26 in the region flanked by and including the markers BMS332 and BM9284. The at least one genetic marker is selected from the group of markers shown in Table 19e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 37.6 cM to about 66.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA26. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA26 in the region flanked by and including the markers RM026 and BM7237. The at least one genetic marker is selected from the group of markers shown in Table 19f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 37.6 cM to about 43.2 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA26. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA26 in the region flanked by and including the markers RM026 and RME40. The at least one genetic marker is selected from the group of markers shown in Table 19g:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 43.2 cM to about 66.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA26. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA26 in the region flanked by and including the markers RME40 and BM7237. The at least one genetic marker is selected from the group of markers shown in Table 19h:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 53.1 cM to about 60.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA26. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA26 in the region flanked by and including the markers IDVGA-59 and BM804. The at least one genetic marker is selected from the group of markers shown in Table 19i:
In one embodiment of the invention the at least one genetic marker is located on the bovine chromosome BTA28. In one specific embodiment of the present invention, the at least one genetic marker is located in the region from about 8.0 cM to about 59.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA28. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA28 in the region flanked by and including the markers BMC6020 and BMC2208. The at least one genetic marker is significant for the calving traits SB, CD and/or CS. In a particular embodiment the at least one genetic marker is significant for example the trait SB, such as CD, for example CS. However, in a further embodiment the at least one genetic marker is significant for the traits in any combination. The at least one genetic marker is selected from the group of markers shown in Table 20a:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 8.0 cM to about 24.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA28. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA28 in the region flanked by and including the markers BMC6020 and BL25. The at least one genetic marker is selected from the group of markers shown in Table 20b:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 16.9 cM to about 24.8 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA28. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA28 in the region flanked by and including the markers ETH1112 and BL25. The at least one genetic marker is selected from the group of markers shown in Table 20c:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 24.8 cM to about 50.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA28. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA28 in the region flanked by and including the markers BL25 and DIK5056. The at least one genetic marker is selected from the group of markers shown in Table 20d:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 38.0 cM to about 45.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA28. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA28 in the region flanked by and including the markers DIK2955 and DIK713. The at least one genetic marker is selected from the group of markers shown in Table 20e:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 38.0 cM to about 43.0 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA28. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA28 in the region flanked by and including the markers DIK2955 and BMS2658. The at least one genetic marker is selected from the group of markers shown in Table 20f:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 43.0 cM to about 59.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA28. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA28 in the region flanked by and including the markers BMS2658 and BMC2208. The at least one genetic marker is selected from the group of markers shown in Table 20g:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 45.9 cM to about 55.9 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA28. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA28 in the region flanked by and including the markers DIK713 and DIK5323. The at least one genetic marker is selected from the group of markers shown in Table 20h:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 49.4 cM to about 50.5 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA28. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA28 in the region flanked by and including the markers BMS1714 and DIK5056. The at least one genetic marker is selected from the group of markers shown in Table 20i:
In a preferred embodiment of the invention, the at least one genetic marker is located in the region from about 55.9 cM to about 59.6 cM (http://www.marc.usda.gov/) on the bovine chromosome BTA28. In one embodiment the at least one genetic marker is located on the bovine chromosome BTA28 in the region flanked by and including the markers DIK5323 and BMC2208. The at least one genetic marker is selected from the group of markers shown in Table 20j:
In another embodiment of the present invention, the at least one genetic marker is a combination of markers, as indicated in tables 20k1 to 20k19. It is understood that the term BTA3, BTA4. BTA5, BTA7, BTA8, BTA9, BTA10, BTA11, BTA12, BTA15, BTA18, BTA19, BTA20, BTA21, BTA22, BTA24, BTA25, BTA26, and BTA28 in tables 20k1 to 20k19 is meant to comprise any regions and genetic markers located on the bovine chromosomes, respectively, as described elsewhere herein.
The tables 20k1 to 20k19 show different embodiments, wherein the combination of markers is a multiplicity of bovine chromosomes, wherein the specific chromosome in each embodiment is indicated with X.
The detection of the presence or absence of a genetic marker allele according to the present invention may be conducted on the DNA sequence of the bovine chromosomes BTA3, BTA4, BTA5, BTA7, BTA8, BTA9, BTA10, BTA11, BTA12, BTA15, BTA18, BTA19, BTA20, BTA21, BTA22, BTA24, BTA25, BTA26, and/or BTA28 specified elsewhere herein according to the present invention or a complementary sequence as well as on transcriptional (mRNA) and translational products (polypeptides, proteins) therefrom.
It will be apparent to the person skilled in the art that there are a large number of analytical procedures which may be used to detect the presence or absence of variant nucleotides at one or more of positions mentioned herein in the specified region. Mutations or polymorphisms within or flanking the specified region can be detected by utilizing a number of techniques. Nucleic acid from any nucleated cell can be used as the starting point for such assay techniques, and may be isolated according to standard nucleic acid preparation procedures that are well known to those of skill in the art. In general, the detection of allelic variation requires a mutation discrimination technique, optionally an amplification reaction and a signal generation system.
A number of mutation detection techniques are listed in Table 21. Some of the methods listed in Table 21 are based on the polymerase chain reaction (PCR), wherein the method according to the present invention includes a step for amplification of the nucleotide sequence of interest in the presence of primers based on the nucleotide sequence of the variable nucleotide sequence. The methods may be used in combination with a number of signal generation systems, a selection of which is also listed in Table 22.
Further amplification techniques are listed in Table 2. Many current methods for the detection of allelic variation are reviewed by Nollau et al., Clin. Chem. 43, 1114-1120, 1997; and in standard textbooks, for example “Laboratory Protocols for Mutation Detection”, Ed. by U. Landegren, Oxford University Press, 1996 and “PCR”, 2nd Edition by Newton & Graham, BIOS Scientific Publishers Limited, 1997.
The detection of genetic markers can according to one embodiment of the present invention be achieved by a number of techniques known to the skilled person, including typing of microsatellites or short tandem repeats (STR), restriction fragment length polymorphisms (RFLP), detection of deletions or insertions, random amplified polymorphic DNA (RAPIDs) or the typing of single nucleotide polymorphisms by methods such as restriction fragment length polymerase chain reaction, allele-specific oligomer hybridisation, oligomer-specific ligation assays, hybridisation with PNA or locked nucleic acids (LNA) probes.
A primer of the present invention is a nucleic acid molecule sufficiently complementary to the sequence on which it is based and of sufficiently length to selectively hybridise to the corresponding region of a nucleic acid molecule intended to be amplified. The primer is able to prime the synthesis of the corresponding region of the intended nucleic acid molecule in the methods described above. Similarly, a probe of the present invention is a molecule for example a nucleic acid molecule of sufficient length and sufficiently complementary to the nucleic acid sequence of interest which selectively binds to the nucleic acid sequence of interest under high or low stringency conditions.
The method according to the present invention includes analyzing a sample of a bovine subject, wherein said sample may be any suitable sample capable of providing the bovine genetic material for use in the method. The bovine genetic material may for example be extracted, isolated and purified if necessary from a blood sample, a tissue samples (for example spleen, buccal smears), clipping of a body surface (hairs or nails), milk and/or semen. The samples may be fresh or frozen.
The sequence polymorphisms of the invention comprise at least one nucleotide difference, such as at least two nucleotide differences, for example at least three nucleotide differences, such as at least four nucleotide differences, for example at least five nucleotide differences, such as at least six nucleotide differences, for example at least seven nucleotide differences, such as at least eight nucleotide differences, for example at least nine nucleotide differences, such as 10 nucleotide differences. The nucleotide differences comprise nucleotide differences, deletion and/or insertion or any combination thereof.
The primers that may be used according to the present invention are shown in Table 22. The in Table 22 specified primer pairs may be used individually or in combination with one or more primer pairs of Table 22.
The design of such primers or probes will be apparent to the molecular biologist of ordinary skill. Such primers are of any convenient length such as up to 50 bases, up to 40 bases, more conveniently up to 30 bases in length, such as for example 8-25 or 8-15 bases in length. In general such primers will comprise base sequences entirely complementary to the corresponding wild type or variant locus in the region. However, if required one or more mismatches may be introduced, provided that the discriminatory power of the oligonucleotide probe is not unduly affected. The primers/probes of the invention may carry one or more labels to facilitate detection.
In one embodiment, the primers and/or probes are capable of hybridizing to and/or amplifying a subsequence hybridizing to a single nucleotide polymorphism containing the sequence delineated by the markers as shown herein.
The primer nucleotide sequences of the invention further include: (a) any nucleotide sequence that hybridizes to a nucleic acid molecule of the delineated region(s) or its complementary sequence or RNA products under stringent conditions, e.g., hybridization to filter-bound DNA in 6× sodium chloride/sodium citrate (SSC) at about 45° C. followed by one or more washes in 0.2×SSC/0.1% Sodium Dodecyl Sulfate (SDS) at about 50-65° C., or (b) under highly stringent conditions, e.g., hybridization to filter-bound nucleic acid in 6×SSC at about 45° C. followed by one or more washes in 0.1×SSC/0.2% SDS at about 68° C., or under other hybridization conditions which are apparent to those of skill in the art (see, for example, Ausubel F. M. et al., eds., 1989, Current Protocols in Molecular Biology, Vol. I, Green Publishing Associates, Inc., and John Wiley & sons, Inc., New York, at pp. 6.3.1-6.3.6 and 2.10.3). Preferably the nucleic acid molecule that hybridizes to the nucleotide sequence of (a) and (b), above, is one that comprises the complement of a nucleic acid molecule of the region s or r or a complementary sequence or RNA product thereof. In a preferred embodiment, nucleic acid molecules comprising the nucleotide sequences of (a) and (b), comprises nucleic acid molecule of RAI or a complementary sequence or RNA product thereof.
Among the nucleic acid molecules of the invention are deoxyoligonucleotides (“oligos”) which hybridize under highly stringent or stringent conditions to the nucleic acid molecules described above. In general, for probes between 14 and 70 nucleotides in length the Melting Temperature™ is calculated using the formula:
Tm(° C.)=81.5+16.6(log [monovalent cations (molar)])+0.41(% G+C)−(500/N)
where N is the length of the probe. If the hybridization is carried out in a solution containing formamide, the melting temperature is calculated using the equation Tm(° C.)=81.5+16.6(log [monovalent cations (molar)])+0.41 (% G+C)−(0.61% formamide)−(500/N) where N is the length of the probe. In general, hybridization is carried out at about 20-25 degrees below Tm (for DNA-DNA hybrids) or 10-15 degrees below Tm (for RNA-DNA hybrids).
Exemplary highly stringent conditions may refer for example to washing in 6×SSC/0.05% sodium pyrophosphate at 37° C. (for about 14-base oligos), 48° C. (for about 17-base oligos), 55° C. (for about 20-base oligos), and 60° C. (for about 23-base oligos). Accordingly, the invention further provides nucleotide primers or probes which detect the r region polymorphisms of the invention. The assessment may be conducted by means of at least one nucleic acid primer or probe, such as a primer or probe of DNA, RNA or a nucleic acid analogue such as peptide nucleic acid (PNA) or locked nucleic acid (LNA).
According to one aspect of the present invention there is provided an allele-specific oligonucleotide probe capable of detecting a polymorphism at one or more of positions in the delineated regions 1.
The allele-specific oligonucleotide probe is preferably 5-50 nucleotides, more preferably about 5-35 nucleotides, more preferably about 5-30 nucleotides, more preferably at least 9 nucleotides.
In order to detect whether the genetic marker is present in the genetic material, standard methods well known to persons skilled in the art may be applied, for example by the use of nucleic acid amplification. In order to determine whether the genetic marker is genetically linked to the calving traits, a permutation test can be applied when the regression method is used (Doerge and Churchill, 1996), or the Piepho-method can be applied (Piepho, 2001) when the variance components method is used. The principle of the permutation test is well described by Doerge and Churchill (1996), whereas the Piepho-method is well described by Piepho (2001). Significant linkage in the within family analysis using the regression method, a 1000 permutations were made using the permutation test (Doerge and Churchill, 1996). A threshold at the 5% chromosome wide level was considered to be significant evidence for linkage between the genetic marker and the calving traits. In addition, the QTL was confirmed in different sire families. For the across family analysis and multi-trait analysis with the variance component method the piepho method was used to determine the significance level (Piepho, 2001). A threshold at the 5% chromosome wide level was considered to be significant evidence for linkage between the genetic marker and the calving traits.
Another aspect of the present invention relates to a diagnostic kit for use in detecting the presence or absence in a bovine subject of at least one genetic marker associated with bovine calving characteristics, comprising at least one oligonucleotide sequence, wherein the nucleotide sequences are selected from any of SEQ ID NO.: 1 to SEQ ID NO.: 558 and/or any combination thereof.
Genotyping of a bovine subject in order to establish the genetic determinants of calving traits for that subject according to the present invention can be based on the analysis of genomic DNA which can be provided using standard DNA extraction methods as described herein. The genomic DNA may be isolated and amplified using standard techniques such as the polymerase chain reaction using oligonucleotide primers corresponding (complementary) to the polymorphic marker regions. Additional steps of purifying the DNA prior to amplification reaction may be included. Thus, a diagnostic kit for establishing calving characteristics comprises, in a separate packing, at least one oligonucleotide sequence selected from the group of sequences shown in table 23 and any combinations thereof.
A total genome scan for QTL affecting calving traits, was carried out in the Danish Holstein population. Marker and phenotypic data were collected according to the granddaughter design (Weller et al., 1990), which included 34 sires with 2042 progeny-tested sons. Numbers of sons per sire ranged from 20 to 106. Sires and their sons were genotyped for marker information whereas phenotypic records were taken from granddaughter performances. Numbers of daughters of each son ranged between 70 and 100. The marker data set included a total of 384 microsatellites covering all 29 Bos Taurus chromosomes.
Purification of genomic DNA
Genomic DNA was purified from semen according to the following protocol:
After thawing the semen-straw, both ends of the straw were cut away with a pair of scissors and the content of semen transferred to a 1.5 ml eppendorf tube. 1 ml of 0.9% NaCl was used to flush the straw into the tube. The tube was then centrifuged for 5 minutes at 2000 rpm, followed by removal of the supernatant. This washing step was repeated twice.
Then 300 μl buffer S (10 mM Tris HCl pH 8, 100 mM NaCl, 10 mM EDTA pH 8; 0.5% SDS), 20 μl 1 M DTT and 20 μl pronase (20 mg/ml) (Boehringer) are added to the tube. After mixing the tubes are incubated over night with slow rotation where after 180 μl saturated NaCl is added followed by vigorous agitation for 15 seconds. The tube is the centrifuged for 15 minutes at 11000 rpm. 0.4 ml of the supernatant is transferred to a 2 ml tube and 1 ml of 96% ethanol is added, mixing is achieved by slow rotation of the tube. The tube is then centrifuged for 10 minutes at 11000 rpm. Remove the supernatant by pouring away the liquid, wash the pellet with 70% ethanol (0.2 ml) and centrifuge again for 10 minutes at 11000 rpm. Pour away the ethanol, dry the pellet and resuspend in 0.5 ml of TE-buffer) for 30 minutes at 55° C.
PCR reactions were run in a volume of 8 μl using TEMPase (GeneChoice) polymerase and reaction buffer I as provided by the supplier (GeneChoice). Usually 5 different markers are included in each multiplex PCR. 1 μl DNA, 0.1 μl TEMPase enzyme, 0.2 mM dNTPs, 1.2 mM MgCl2, 0.3 μM each primer.
The PCR mixtures were subjected to initial denaturation at 94° C. for 15 min (for TEMPase). Subsequently, the samples were cycled for 10 cycles with touchdown, i.e. the temperature is lowered 1° C. at each cycle (denaturation at 94° C. 30″, annealing at 67° C. 45″, elongation 72° C. 30″), after which the samples were cycled for 20 cycles with normal PCR conditions (denaturation at 94° C. 30″, annealing at 58° C. 45″, elongation 72° C. 30) PCR cycling was terminated by I cycle at 72° C. 30′ and the PCR machine was programmed to cooling down the samples at 4° C. for ‘ever’.
The nucleotide sequence of the primers used for detecting the markers is shown in Table 23. The sequence is listed from the 5′ end.
0.5 μl PCR-product is added to 9.5 μl formamide and analysed on an ABI-3730XL sequencing Instrument (Applied Biosystems Inc.).
The calving traits considered were stillbirth (SB), calving difficulty (CD) and the size of calf at birth (CS) after first calving. The traits were assessed both as a “direct’ effect (D) of the sire in the calf and as a “maternal” effect (M) of the sire in the mother of the calf, giving a total of 6 traits for the QTL analysis. Breeding values for each trait were obtained from the Danish Agricultural Advisory Service database. The breeding values were obtained from the routine breeding value estimation procedure by the exception that information from correlated traits and pedigree information were ignored.
The calving traits were analyzed using the linear regression mapping procedure of Haley & Knott (1992). Significant QTL were found by using permutation tests developed by Churchill & Doerge (1994). In this procedure traits and chromosomes were analyzed separately and tested for the presence of a single QTL affecting a particular trait. If the test: (1) exceeds the 5% chromosome-wise significance threshold and (2) the QTL-region affecting two or more traits, then the QTL is retained for further characterization. The variance component QTL mapping approach was used to test if it is a single pleiotropic QTL affecting two traits or two linked QTL affecting different traits. The QTL is modeled as a random effect in a bivariate linear mixed model that adjusts for polygenenic and overall trait means. The IBD matrices were computed using a recursive algorithm (Sørensen et al., 2003, Wang et al., 1995), conditional on the most likely marker linkage phase in the sire. The IBD matrices were computed for every 2 cM along the chromosomes and used in the subsequent variance component estimation procedure.
Baysian information criterion (BIC) and correlation between the QTL (rq) were used to compare the pleiotropic and linked model.
The chromosome-wise regression test (table 24) showed a total of 27 significant QTL for calving traits in first lactation on 17 different chromosomes. 15 of the QTL were related to direct calving ease and 12 QTL was related to the maternal effects.
Average number of informative markers per grandsire family varied from 3.0 (BTA25) to 8.5 (BTA3) informative markers per chromosome.
anumbers of informative markers,
bnumber of analyzed grandsires,
cp-values
Each QTL was detected significant in 0 to 7 Holstein families when the test was performed within family analysis. BTA 28 showed no significant families for M_SB, but four families were candidates to significance (p<0.10).
Seven chromosomes showed more than one significant QTL in the same region and were further examined for the presence of pleiotropic or linked QTL. Only BTA 18 showed more than two significant QTL.
Table 25 shows results of tests to distinguish between pleiotropic and linked QTL. Two regions (BTA 12, BTA25) indicate QTL with pleiotropic effects with strong correlations between the traits (close to 1 or −1). For BTA7 and BTA26 the linkage model is in favor with correlations closer to 0 and high BIC-values. The analysis on BTA22 and BTA28 could not clarify whether it is linked or pleiotropic QTL. BTA8 did not give useful results because the likelihood did not converge to a maximum. On BTA 18 there may be a pleiotropic QTL affecting all the direct calving traits and probably one QTL affecting maternal stillbirth (M_SB).
aaverage number of informative markers between QTL,
bprobability of a pleiotropic model over the linked model
Several QTL affecting both direct and maternal calving traits were identified. The QTL for D_CD on BTA8 confirmed the result in Ashwell et al (2003) and the QTL for direct and maternal stillbirth on BTA7 and BTA18 confirmed the results in Kuhn et al (2003). The multi-trait and multiple QTL variance component approach detected two pleiotropic QTL affecting both direct calving size and calving difficulties, and two pleiotropic QTL affecting both direct and maternal stillbirth. The identified QTL could have important implications for the Danish Holstein breeding program because of relative high economic weight in the combined selection index. In particular, QTL affecting survival and stillbirth without affecting calf size will be an efficient way to improve genetic progress for calving traits. More marker information is needed to get a more precise characterization of the QTL, before it can be used for effective selection purposes.
Number | Date | Country | Kind |
---|---|---|---|
PA 2006 00181 | Feb 2006 | DK | national |
PA 2007 00165 | Jan 2007 | DK | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
---|---|---|---|---|
PCT/DK2007/000060 | 2/5/2007 | WO | 00 | 11/6/2008 |