Identification of candidate markers on bovine chromosome 14 (BTA14) under milk production trait quantitative trait loci in Holstein.

The objective of this study was to identify single-nucleotide polymorphisms using a bovine chromosome 14 high-density SNP panel after accounting for the effect of DGAT1. Linkage disequilibrium information and sire heterozygosity were used to select markers for linkage analysis on bovine chromosome 14 for milk production traits in 321 Holstein animals. Results show putative milk peaks at 42 and 61 cM, both at p<0.10, a fat yield peak at 42 and 63 cM, both at p<0.05; a protein yield peak at 42 (p<0.01) and 84 cM (p<0.05); fat per cent peaks at 3 (p<0.01) and 29 cM (p<0.05), and a protein per cent peak at 4 cM (p<0.05). Once quantitative trait loci positions were established, allele substitution effects for all markers were evaluated using the same statistical model. Overlaying information between quantitative trait loci (QTL) and allele effect analysis enabled the identification (p<0.01) of 20 SNPs under the milk yield QTL, 2 under both of the fat yield peaks, 8 and 9 under the protein yield peaks, 2 and 6 for the fat per cent peaks and 5 for the protein per cent peak. One SNP in particular, ss61514555:A>C, showed association with 3 of the 5 traits: milk (p=1.59E-04), fat (p=6.88E-05) and protein yields (p=5.76E-05). Overall, combining information from linkage disequilibrium, sire heterozygosity and genetic knowledge of traits enabled the characterization of additional markers with significant associations with milk production traits.

A whole genome scan to map QTL for milk production traits and somatic cell score in Canadian Holstein bulls.

The detection and mapping of genetic markers linked to quantitative trait loci (QTL) can be utilized to enhance genetic improvement of livestock populations. With the completion of the bovine genome sequence assembly, single nucleotide polymorphisms (SNP) assays spanning the whole bovine genome and research work on large scale identification, validation and analysis of genotypic variation in cattle has become possible. The objective of the present study was to perform a whole genome scan to identify and map QTL affecting milk production traits and somatic cell scores using linkage disequilibrium (LD) regression and 1536 SNP markers. Three and 18 SNP were found to be associated with only milk yield (MY) at a genome and chromosome wise significance (p < 0.05) level respectively. Among the 21 significant SNP, 16 were in a region reported to have QTL for MY in other dairy cattle populations and while the rest five were new QTL finding. Four SNP out of 21 are significant for the milk production traits (MY, fat yield, protein yield (PY), and milk contents) in the present study. Six and nine SNP were associated with PY at a genome and chromosome wise significant (p < 0.05) level respectively. Three and 17 SNP were found to be associated with FY at a genome and chromosome wise significant (p < 0.05) level. Five and seven SNP were mapped with somatic cell score at a genome and chromosome wise significant (p < 0.05) level respectively. The results of this study have revealed QTL for MY, PY, protein percentage, FY, fat percentage, somatic cell score and persistency of milk in the Canadian dairy cattle population. The chromosome regions identified in this study should be further investigated to potentially identify the causative mutations underlying the QTL.

Linkage disequilibrium and signatures of selection on chromosomes 19 and 29 in beef and dairy cattle.

The objective of this study was to quantify the extent of linkage disequilibrium (LD) on bovine chromosomes 19 and 29 and to study the pattern of selection signatures in beef and dairy breeds (Angus and Holstein) of Bos taurus. The extent of LD was estimated for 370 and 186 single nucleotide polymorphism markers on BTA19 and 29 respectively using the square of the correlation coefficient (r(2)) among alleles at pairs of loci. A comparison of the extent of LD found that the decline of LD followed a similar pattern in both breeds. We observed long-range LD and found that LD dissipates to background levels at a locus separation of about 20 Mb on both chromosomes. Along each chromosome, patterns of LD were variable in both breeds. We find that a minimum of 30 000 informative and evenly spaced markers would be required for whole-genome association studies in cattle. In addition, we have identified chromosomal regions that show some evidence of selection for economically important traits in Angus and Holstein cattle. The results of this study are of importance for the design and application of association studies.

A whole-genome scan to map quantitative trait loci for conformation and functional traits in Canadian Holstein bulls.

Genetic improvement of livestock populations can be achieved through detection and mapping of genetic markers linked to quantitative trait loci (QTL). With the completion of the bovine genome sequence assembly, single nucleotide polymorphism (SNP) assays spanning the whole bovine genome and research work on large-scale identification, validation, and analysis of genotypic variation in cattle has become possible. A total of 462 Canadian Holstein Bulls were used to test the association between SNP and QTL. Single locus linkage disequilibrium regression model was implemented to perform a whole genome scan to identify and map QTL affecting conformation and functional traits. One thousand five hundred thirty-six SNP markers from introns and exons of potential QTL regions for economically important traits across the bovine genome were selected for association analysis. A total of 45 and 151 SNP were found to be associated with 17 conformation and functional traits at a genome- and chromosome-wise significance level, respectively. Among the 196 significant SNP, 169 of them are newly detected in this study, whereas 27 of them have been reported in previous literature and 161 of these were located in genes and are worth further investigating to potentially identify the causative mutations underlying the QTL. The single locus linkage disequilibrium regression method using SNP marker genotypes has proven to be a successful methodology for detecting and mapping QTL in dairy cattle populations.

Estimation of genome-wide haplotype effects in half-sib designs.

Genome-wide estimated breeding values can be computed from the simultaneous estimates of the effects of small intervals of DNA throughout the genome on a trait or traits of interest. Small intervals or segments of DNA can be created by the use of thousands of single nucleotide polymorphisms (SNP) available in panels of 10, 25 and 50 thousand SNP. A simulation study was conducted to compare factors that could influence the accuracy of genome-wide selection. Factors studied were the heritability of the trait, dispersion of quantitative trait loci (QTL) across the genome and size of the QTL effects. A 100-cM genome was assumed with 100 equally spaced SNP markers and 10 QTL. A granddaughter design was constructed with 20 sires and 100 sons per sire. Population-wide linkage disequilibrium was assumed to be sufficient after 25 generations of random mating starting with 30 sires and 400 dams. Best linear unbiased prediction was used to simultaneously estimate the effects of 99 SNP intervals, based on determining the SNP haplotype of each son inherited from the sire. Indicator variables were used in the model to indicate haplotype transmission. A genome-wide estimated breeding value was calculated as the sum of the appropriate haplotype interval estimates for each son. Correlations between estimated and true breeding values ranged from 0.60 to 0.79. Situations with unequally sized QTL effects and randomly dispersed QTL gave higher correlations. QTL positions could be estimated to within 2 cM or less.

Transmission disequilibrium test for quantitative trait loci detection in livestock populations.

The performance of several transmission disequilibrium tests (TDT) for detection of quantitative trait loci (QTL) in data structures typical of outbred livestock populations were investigated. Factorial mating designs were simulated with 10 sires mated to either 50 or 200 dams, each family having five or eight full sibs. A single marker and QTL, both bi-allelic, were simulated using a disequilibrium coefficient based on complete initial disequilibrium and 50 generations of recombination [i.e. D = D(0)(1 - theta)50], where theta is the recombination fraction between marker and QTL. The QTL explained either 10% (small QTL) or 30% (large QTL) of the genetic variance for a trait with heritability of 0.3. Methods were: TDT for QTL (Q-TDT; both parents known), 1-TDT (only one parent known) and sibling-based TDT (S-TDT; neither parent known, but sibs available). All were found to be effective tests for association and linkage between the QTL and a tightly linked marker (theta < 0.02) in these designs. For a large QTL, theta = 0.01, and five full sibs per family, the empirical power for Q-TDT, 1-TDT and S-TDT was 0.966, 0.602 and 0.974, respectively, in a large population, versus 0.700, 0.414 and 0.654, respectively, in a small population. For a small QTL effect, theta = 0.01, large population the empirical power of these tests were 0.709, 0.287 and 0.634. The power of Q-TDT, 1-TDT and S-TDT was satisfactory for large populations, for QTL with large effects and for five full sibs per family. The 1-TDT based on a linear model was more powerful than the normal 1-TDT. The empirical power for Q-TDT and 1-TDT with a linear model was 0.978 and 0.995 respectively. TDT based on analogous linear models, incorporating the polygenic covariance structure, provided only small increases in power compared with the usual TDT for QTL.