Multisite haplotype on cattle chromosome 3 is associated with quantitative trait locus effects on lactation traits.

The goal of this study was to identify candidate genes and DNA polymorphisms for quantitative trait loci (QTL) affecting milk yield (MY), fat yield (FY), and protein yield (PY) previously mapped to bovine chromosome 3 (BTA3). To accomplish this, 373 half-siblings sired by three bulls previously shown to be segregating for lactation trait QTL, and 263 additional sires in the U.S. Dairy Bull DNA Repository (DBDR) were genotyped for 2,500 SNPs within a 16.3 Mbp QTL critical region on BTA3. Targeted resequencing of ∼1.8 Mbp within the QTL critical region of one of the QTL heterozygous sires identified additional polymorphisms useful for association studies. Twenty-three single nucleotide polymorphisms (SNPs) within a fine-mapped region were associated with effects on breeding values for MY, FY, or PY in DBDR sires, of which five SNPs were in strong linkage disequilibrium in the population. This multisite haplotype included SNPs located within exons or promoters of four tightly linked genes: RAP1A, ADORA3, OVGP1, and C3H1orf88. An SNP within RAP1A showed strong evidence of a recent selective sweep based on integrated haplotype score and was also associated with breeding value for PY. Because of its known function in alveolar lumen formation in the mammary gland, RAP1A is thus a strong candidate gene for QTL effects on lactation traits. Our results provide a detailed assessment of a QTL region that will be a useful guide for complex traits analysis in humans and other noninbred species.

Cohen-Zinder M ，Donthu R ，Larkin DM ，Kumar CG ，Rodriguez-Zas SL ，Andropolis KE ，Oliveira R ，Lewin HA ... -  《-》

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 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 ... -  《-》

Detection of quantitative trait loci influencing dairy traits using a model for longitudinal data.

A longitudinal-linkage analysis approach was developed and applied to an outbred population. Nonlinear mixed-effects models were used to describe the lactation patterns and were extended to include marker information following single-marker and interval mapping models. Quantitative trait loci (QTL) affecting the shape and scale of lactation curves for production and health traits in dairy cattle were mapped in three U.S. Holstein families (Dairy Bull DNA Repository families one, four, and five) using the granddaughter design. Information on 81 informative markers on six Bos taurus autosomes (BTA) was combined with milk yield, fat, and protein percentage and somatic cell score (SCS) test-day records. Six percent of the single-marker tests surpassed the experiment-wise significance threshold. Marker BL41 on BTA3 was associated with decrease in milk yield during mid-lactation in family one. The scale and shape of the protein percentage lactation curve in family four varied with BMC4203 (BTA6) allele that the son received from the grandsire. Some map locations were associated with variation in the lactation pattern of multiple traits. In family four, the marker HUJI177 (BTA3) was associated with changes in the milk yield and protein percentage curves suggesting a QTL with pleiotropic effects or multiple QTL in the region. The interval mapping model uncovered a QTL on BTA7 associated with variation in milk-yield pattern in family four and a QTL on BTA21 affecting SCS in family five. The developed approach can be extended to random regressions, covariance functions, spline, gametic and variance component models. The results from the longitudinal-QTL approach will help to understand the genetic factors acting at different stages of lactation and will assist in positional candidate gene research. Identified positions can be incorporated into marker-assisted selection decisions to alter the persistency and peak production or the fluctuation of SCS during a lactation.

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

Fine mapping quantitative trait loci affecting milk production traits on bovine chromosome 6 in a Chinese Holstein population.

To fine map the previously detected quantitative trait loci (QTLs) affecting milk production traits on bovine chromosome 6 (BTA6), 15 microsatellite markers situated within an interval of 14.3 cM spanning from BMS690 to BM4528 were selected and 918 daughters of 8 sires were genotyped. Two mapping approaches, haplotype sharing based LD mapping and single marker regression mapping, were used to analyze the data. Both approaches revealed a quantitative trait locus (QTL) with significant effects on milk yield, fat yield and protein yield located in the segment flanked by markers BMS483 and MNB209, which spans a genetic distance of 0.6 cM and a physical distance of 1.5 Mb. In addition, the single marker regression mapping also revealed a QTL affecting fat percentage and protein percentage at marker DIK2291. Our fine mapping work will facilitate the cloning of candidate genes underlying the QTLs for milk production traits.

Mei G ，Yin C ，Ding X ，Zhang Q ... -  《Journal of Genetics and Genomics》