Combining evidence of selection with association analysis increases power to detect regions influencing complex traits in dairy cattle

Abstract

BackgroundHitchhiking mapping and association studies are two popular approaches to map genotypes to phenotypes. In this study we combine both approaches to complement their specific strengths and weaknesses, resulting in a method with higher statistical power and fewer false positive signals. We applied our approach to dairy cattle as they underwent extremely successful selection for milk production traits and since an excellent phenotypic record is available. We performed whole genome association tests with a new mixed model approach to account for stratification, which we validated via Monte Carlo simulations. Selection signatures were inferred with the integrated haplotype score and a locus specific permutation based integrated haplotype score that works with a folded frequency spectrum and provides a formal test of signifance to identify selection signatures.ResultsAbout 1,600 out of 34,851 SNPs showed signatures of selection and the locus specific permutation based integrated haplotype score showed overall good accordance with the whole genome association study. Each approach provides distinct information about the genomic regions that influence complex traits. Combining whole genome association with hitchhiking mapping yielded two significant loci for the trait protein yield. These regions agree well with previous results from other selection signature scans and whole genome association studies in cattle.ConclusionWe show that the combination of whole genome association and selection signature mapping based on the same SNPs increases the power to detect loci influencing complex traits. The locus specific permutation based integrated haplotype score provides a formal test of significance in selection signature mapping. Importantly it does not rely on knowledge of ancestral and derived allele states.

Association of 20 candidate gene markers with milk production and composition traits in sires of Reggiana breed, a local dairy cattle population

“…The absence of any detectable effect on MY could be due to different haplotype structures around DGAT1 in the Reggiana cattle that might reduce, or counterbalance, the effect of the p.K232A substitution on this trait. A complex QTL pattern spanning the telomeric region of BTA14, that might be only in part explained by the VNTR polymorphism in the DGAT1 promoter region (Kühn et al, 2004), has been evidenced in Holstein and Brown Swiss cattle (Fontanesi et al, 2005;Schwarzenbacher et al, 2012). Additional studies are needed to explain the results in the Reggiana breed, in which no sires with KK genotype were observed.…”

Genetic characterization of a core collection of flax (Linum usitatissimum L.) suitable for association mapping studies and evidence of divergent selection between fiber and linseed types

“…As an effect of genetic hitchhiking, loci closely linked to beneficial alleles might present distortions from neutral expectations. Genome scans have allowed the identification of candidate loci involved in domestication and breeding traits in several crops [47,51] and domesticated animals [52,53]. However, population structure and bottlenecks can mimic the effect of selection and create false positives.…”

“…Currently, next generation sequencing technology enables the re-sequencing of a large number of accessions at a reasonable price. Thus, high quality and dense single nucleotide polymorphism (SNP) markers promise to provide comprehensive genome coverage for the identification of non-neutral genomic regions in flax [53]. Such genomic tools for flax genetic studies are being developed and more comprehensive genomic scans will be possible in the near future.…”

Analysis of extended haplotype in Korean cattle (Hanwoo) population

“…Qanbari et al performed a whole genome scan for selection signatures in the Holstein genome and then detected a set of 10 candidate regions, including diacylglycerol O-acyltransferase 1, casein cluster, growth hormone receptor, somatostatin, and leptin receptor (6), based on extended haplotype homozygosities (EHHs). More recently, based on EHHs, Schwarzenbacher et al (2012) demonstrated a combination of association analyses and selection signatures in dairy cattle (7); Gautier et al (2011) looked for footprints of selection within a creole cattle breed (8); MacEachern et al reported the results of a comparison of allelic frequencies between Australian Angus and Holstein cattle (9); Flori et al (2009) (10) and Hayes et al (2009) (11) also reported that the growth hormone recepeor (GHR) gene on Bos taurus autosome (BTA) 20 has selection evidence by comparing Holstein breeds, Angus and Holstein; and Gautier et al (2009) performed a whole genome Bayesian scan in West African cattle (12). The aim of this study is to compare EHHs of brown and brindle Hanwoo.…”