Multi-trait meta-analyses reveal 25 quantitative trait loci for economically important traits in Brown Swiss cattle.

Little is known about the genetic architecture of economically important traits in Brown Swiss cattle because only few genome-wide association studies (GWAS) have been carried out in this breed. Moreover, most GWAS have been performed for single traits, thus not providing detailed insights into potentially existing pleiotropic effects of trait-associated loci. To compile a comprehensive catalogue of large-effect quantitative trait loci (QTL) segregating in Brown Swiss cattle, we carried out association tests between partially imputed genotypes at 598,016 SNPs and daughter-derived phenotypes for more than 50 economically important traits, including milk production, growth and carcass quality, body conformation, reproduction and calving traits in 4578 artificial insemination bulls from two cohorts of Brown Swiss cattle (Austrian-German and Swiss populations). Across-cohort multi-trait meta-analyses of the results from the single-trait GWAS revealed 25 quantitative trait loci (QTL; P < 8.36 × 10) for economically relevant traits on 17 Bos taurus autosomes (BTA). Evidence of pleiotropy was detected at five QTL located on BTA5, 6, 17, 21 and 25. Of these, two QTL at BTA6:90,486,780 and BTA25:1,455,150 affect a diverse range of economically important traits, including traits related to body conformation, calving, longevity and milking speed. Furthermore, the QTL at BTA6:90,486,780 seems to be a target of ongoing selection as evidenced by an integrated haplotype score of 2.49 and significant changes in allele frequency over the past 25 years, whereas either no or only weak evidence of selection was detected at all other QTL. Our findings provide a comprehensive overview of QTL segregating in Brown Swiss cattle. Detected QTL explain between 2 and 10% of the variation in the estimated breeding values and thus may be considered as the most important QTL segregating in the Brown Swiss cattle breed. Multi-trait association testing boosts the power to detect pleiotropic QTL and assesses the full spectrum of phenotypes that are affected by trait-associated variants.

Fang ZH ，Pausch H 《BMC GENOMICS》

Distinguishing pleiotropy from linked QTL between milk production traits and mastitis resistance in Nordic Holstein cattle.

Production and health traits are central in cattle breeding. Advances in next-generation sequencing technologies and genotype imputation have increased the resolution of gene mapping based on genome-wide association studies (GWAS). Thus, numerous candidate genes that affect milk yield, milk composition, and mastitis resistance in dairy cattle are reported in the literature. Effect-bearing variants often affect multiple traits. Because the detection of overlapping quantitative trait loci (QTL) regions from single-trait GWAS is too inaccurate and subjective, multi-trait analysis is a better approach to detect pleiotropic effects of variants in candidate genes. However, large sample sizes are required to achieve sufficient power. Multi-trait meta-analysis is one approach to deal with this problem. Thus, we performed two multi-trait meta-analyses, one for three milk production traits (milk yield, protein yield and fat yield), and one for milk yield and mastitis resistance. For highly correlated traits, the power to detect pleiotropy was increased by multi-trait meta-analysis compared with the subjective assessment of overlapping of single-trait QTL confidence intervals. Pleiotropic effects of lead single nucleotide polymorphisms (SNPs) that were detected from the multi-trait meta-analysis were confirmed by bivariate association analysis. The previously reported pleiotropic effects of variants within the DGAT1 and MGST1 genes on three milk production traits, and pleiotropic effects of variants in GHR on milk yield and fat yield were confirmed. Furthermore, our results suggested that variants in KCTD16, KCNK18 and ENSBTAG00000023629 had pleiotropic effects on milk production traits. For milk yield and mastitis resistance, we identified possible pleiotropic effects of variants in two genes, GC and DGAT1. Multi-trait meta-analysis improves our ability to detect pleiotropic interactions between milk production traits and identifies variants with pleiotropic effects on milk production traits and mastitis resistance. In particular, this should contribute to better understand the biological mechanisms that underlie the unfavorable genetic correlation between milk yield and mastitis.

Cai Z ，Dusza M ，Guldbrandtsen B ，Lund MS ，Sahana G ... -  《-》

Genome-wide association studies of fertility and calving traits in Brown Swiss cattle using imputed whole-genome sequences.

Frischknecht M ，Bapst B ，Seefried FR ，Signer-Hasler H ，Garrick D ，Stricker C ，Intergenomics Consortium ，Fries R ，Russ I ，Sölkner J ，Bieber A ，Strillacci MG ，Gredler-Grandl B ，Flury C ... -  《BMC GENOMICS》

Quantitative trait loci affecting milk yield and protein percentage in a three-country Brown Swiss population.

Bagnato A ，Schiavini F ，Rossoni A ，Maltecca C ，Dolezal M ，Medugorac I ，Sölkner J ，Russo V ，Fontanesi L ，Friedmann A ，Soller M ，Lipkin E ... -  《-》

Comparison of two multi-trait association testing methods and sequence-based fine mapping of six additive QTL in Swiss Large White pigs.

Nosková A ，Mehrotra A ，Kadri NK ，Lloret-Villas A ，Neuenschwander S ，Hofer A ，Pausch H ... -  《BMC GENOMICS》