Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals

Abstract

Stature is affected by many polymorphisms of small effect in humans . In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP-seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals.

Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data

“…This genomic region encompasses the DCAF16, FAM184B, LAP3, LCORL, MED28 and NCAPG genes, and the window with the largest CLR value overlapped the NCAPG gene(Figure 5a & 5c). This signature of selection coincides with a QTL that is associated with stature, feed efficiency and fetal growth[61][62][63]. Most SNPs detected within this region were fixed for the alternate allele in the OB cattle of the present study.…”

“…important traits, we investigated if such variants segregate in the sequenced OB cattle although they were not detected in the signature of selection analyses. A number of variants in high linkage disequilibrium stimulate the expression of PLAG1, thus increasing pre-and postnatal growth in cattle[62,63,98]. The OB key ancestors sequenced in our study are fixed for the stature-decreasing alleles at six variants whereas other candidate causal variants are either fixed for the stature-increasing allele or segregate at low allele frequency indicating that a recombinant haplotype might segregate in Swiss OB cattle that could allow for further fine-mapping of that region (Additional File 13).…”

A guinea fowl genome assembly provides new evidence on evolution following domestication and selection in galliformes

“…PAPPA2 was reported as a strong candidate for a QTL affecting body size in mice (Christians, Hoeflich, & Keightley, ) and was also among the 180 loci detected in a GWAS on human adult height performed on close to 200,000 individuals (Lango Allen et al., ). Finally, effects of PAPPA2 on female reproduction performances (Hawken et al., ) and also on adult height (Bouwman et al., ) were observed in cattle. Thus, PAPPA2 is involved in genetic control of body size in three vertebrate species.…”

Quantifying the contribution of sequence variants with regulatory and evolutionary significance to 34 bovine complex traits

“…To test the generality of the findings in humans it is desirable to have another species with very large sample size and cattle is a possible example. There are over 1.46 billion cattle worldwide (3) and millions are being genotyped or whole genome sequenced and phenotyped (4,5). Cattle have been domesticated from two subspecies of the humpless taurine (Bos taurus) and humped zebu (Bos indicus), which diverged approximately 0.5 million years ago from extinct wild aurochs (Bos primigenius) (6).…”