A genome scan to detect quantitative trait loci for economically important traits in Holstein cattle using two methods and a dense single nucleotide polymorphism map.

Genome scans for detection of bovine quantitative trait loci (QTL) were performed via variance component linkage analysis and linkage disequilibrium single-locus regression (LDRM). Four hundred eighty-four Holstein sires, of which 427 were from 10 grandsire families, were genotyped for 9,919 single nucleotide polymorphisms (SNP) using the Affymetrix MegAllele GeneChip Bovine Mapping 10K SNP array. A hybrid of the grand-daughter and selective genotyping designs was applied. Four thousand eight hundred fifty-six of the 9,919 SNP were located to chromosomes in base-pairs and formed the basis for the analyses. The mean polymorphism information content of the SNP was 0.25. The SNP centimorgan position was interpolated from their base-pair position using a microsatellite framework map. Estimated breeding values were used as observations, and the following traits were analyzed: 305-d lactation milk, fat, and protein yield; somatic cell score; herd life; interval of calving to first service; and age at first service. The variance component linkage analysis detected 102 potential QTL, whereas LDRM analysis found 144 significant SNP associations after accounting for a 5% false discovery rate. Twenty potential QTL and 49 significant SNP associations were in close proximity to QTL cited in the literature. Both methods found significant regions on Bos taurus autosome (BTA) 3, 5, and 16 for milk yield; BTA 14 and 19 for fat yield; BTA 1, 3, 16, and 28 for protein yield; BTA 2 and 13 for calving to first service; and BTA 14 for age at first service. Both approaches were effective in detecting potential QTL with a dense SNP map. The LDRM was well suited for a first genome scan due to its approximately 8 times lower computational demands. Further fine mapping should be applied on the chromosomal regions of interest found in this study.

Daetwyler HD ，Schenkel FS ，Sargolzaei M ，Robinson JA ... -  《-》

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.

Kolbehdari D ，Wang Z ，Grant JR ，Murdoch B ，Prasad A ，Xiu Z ，Marques E ，Stothard P ，Moore SS ... -  《-》

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.

Kolbehdari D ，Wang Z ，Grant JR ，Murdoch B ，Prasad A ，Xiu Z ，Marques E ，Stothard P ，Moore SS ... -  《-》

Interval and composite interval mapping of somatic cell score, yield, and components of milk in dairy cattle.

Single-marker, interval-mapping (IM) and composite interval mapping (CIM) were used to detect quantitative trait loci (QTL) controlling milk, fat and protein yields, and somatic cell score (SCS). A granddaughter design was used to combine molecular genetic information with predicted transmitting abilities (PTA) and estimated daughter yield deviations (DYD) from eight Dairy Bull DNA Repository Holstein families. Models that included and excluded weights accounting for the uncertainty of the response variable were evaluated in each trait, family and phenotype (DYD and PTA) combination. The genotypic information consisted of 174 microsatellite markers along 29 Bos taurus autosomes. The average number of informative markers per autosome was three and the number of informative sons per family and marker varied between 21 and 173. Within-family results from the least squares single-marker analyses were used in expectation-maximization likelihood IM and CIM implemented with QTL Cartographer. Different CIM model specifications, offering complementary control on the background QTL outside the interval under study, were evaluated. Permutation techniques were used to calculate the genome-wide threshold test statistic values based on 1,000 samples. Results from the DYD and PTA analyses were highly consistent across traits and families. The minor differences in the estimates from the models that accounted for or ignored the uncertainty of the DYD (variance) and PTA (inverse of reliability) may be associated to the elevated and consistent precision of the DYD and PTA among sons. The CIM model best supported by the data had 10 markers controlling for background effects. On autosome (BTA) three, a QTL at 32 cM influencing protein yield was located in family five and a QTL at 74 cM for fat yield was located in family eight. Two map positions associated with SCS were detected on BTA 21, one at 33 cM in family one and the other at 84 cM in family three. A QTL for protein yield was detected between 26 and 36 cM on BTA six, family six, and a QTL for milk yield was detected at 116 cM on BTA seven in family three. The IM and CIM approaches detected a QTL at 3 cM on BTA 14 influencing fat yield in family four. Two map positions on BTA 29 were associated with significant variation of milk (0 cM) and fat yield (14 cM) in family seven. These results suggest the presence of one QTL with pleiotropic effects on multiple traits or multiple QTL within the marker interval. Findings from this study could be used in subsequent fine-mapping work and applied to marker-assisted selection of dairy production and health traits.

Rodriguez-Zas SL ，Southey BR ，Heyen DW ，Lewin HA ... -  《JOURNAL OF DAIRY SCIENCE》

Quantitative trait loci mapping of calving and conformation traits on Bos taurus autosome 18 in the German Holstein population.

Linkage, linkage disequilibrium, and combined linkage and linkage disequilibrium analyses were performed to map quantitative trait loci (QTL) affecting calving and conformation traits on Bos taurus autosome 18 (BTA18) in the German Holstein population. Six paternal half-sib families consisting of a total of 1,054 animals were genotyped on 28 genetic markers in the telomeric region on BTA18 spanning approximately 30 Mb. Calving traits, body type traits, and udder type traits were investigated. Using univariately estimated breeding values, maternal and direct effects on calving ease and stillbirth were analyzed separately for first- and further-parity calvings. The QTL initially identified by separate linkage and linkage disequilibrium analyses could be confirmed by a combined linkage and linkage disequilibrium analysis for udder composite index, udder depth, fore udder attachment, front teat placement, body depth, rump angle, and direct effects on calving ease and stillbirth. Concurrence of QTL peaks and a similar shape of restricted log-likelihood ratio profiles were observed between udder type traits and for body depth and calving traits, respectively. Association analyses were performed for markers flanking the most likely QTL positions by applying a mixed model including a fixed allele effect of the maternally inherited allele and a random polygenic effect. Results indicated that microsatellite marker DIK4234 (located at 53.3 Mb) is associated with maternal effects on stillbirth, direct effects on calving ease, and body depth. A comparison of effects for maternally inherited DIK4234 alleles indicated a favorable, positive correlation of maternal and direct effects on calving. Additionally, the association of maternally inherited DIK4234 marker alleles with body depth implied that conformation traits might provide the functional background of the QTL for calving traits. For udder type traits, the strong coincidence of QTL peaks and the position of the QTL in a region previously reported to harbor QTL for somatic cell score indicated that effects of QTL for udder type traits might be correlated with effects of QTL for udder health traits on BTA18. Our results suggest that loci in the middle to telomeric region on BTA18 with effect on conformation traits may also contribute to the genetic variance of calving and udder health traits. Further analyses are required to identify the causal mutations affecting conformation and calving traits and to investigate the correlation of effects for loci associated with conformation, calving, and udder health traits.

Brand B ，Baes C ，Mayer M ，Reinsch N ，Seidenspinner T ，Thaller G ，Kühn Ch ... -  《-》