Evidence for and localization of proposed causative variants in cattle and pig genomes

Martin Johnsson,Melissa K Jungnickel

doi:10.1186/s12711-021-00662-x

Martin Johnsson, Melissa K Jungnickel

Open Access

https://doi.org/10.1186/s12711-021-00662-x

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Abstract

BackgroundThis paper reviews the localization of published potential causative variants in contemporary pig and cattle reference genomes, and the evidence for their causality. In spite of the difficulties inherent to the identification of causative variants from genetic mapping and genome-wide association studies, researchers in animal genetics have proposed putative causative variants for several traits relevant to livestock breeding.ResultsFor this review, we read the literature that supports potential causative variants in 13 genes (ABCG2, DGAT1, GHR, IGF2, MC4R, MSTN, NR6A1, PHGK1, PRKAG3, PLRL, RYR1, SYNGR2 and VRTN) in cattle and pigs, and localized them in contemporary reference genomes. We review the evidence for their causality, by aiming to separate the evidence for the locus, the proposed causative gene and the proposed causative variant, and report the bioinformatic searches and tactics needed to localize the sequence variants in the cattle or pig genome.ConclusionsTaken together, there is usually good evidence for the association at the locus level, some evidence for a specific causative gene at eight of the loci, and some experimental evidence for a specific causative variant at six of the loci. We recommend that researchers who report new potential causative variants use referenced coordinate systems, show local sequence context, and submit variants to repositories.

Highlights

To localise putative causative variants in contemporary reference genomes, we used the Ensembl Genes [13] and Ensembl Variation [14] database version 102
Quantitative traits are affected by many variants each with a small effect, which limits the power of genetic mapping, even with large sample sizes
The genomic resolution of genetic mapping is limited by the correlation between genetic variants, meaning that there are many candidate genes and variants for each association

Summary

Introduction

To localise putative causative variants in contemporary reference genomes, we used the Ensembl Genes [13] and Ensembl Variation [14] database version 102. In spite of the difficulties inherent to the identification of causative variants from genetic mapping and genome-wide association studies, researchers in animal genetics have proposed putative causative variants for several traits relevant to livestock breeding. Identification of causative variants from genetic mapping and genome-wide association studies is a difficult problem, especially for quantitative traits. In commercial livestock breeds that have seen systematic breeding, familial relationship leads to linkage disequilibrium that can extend In spite of these difficulties, researchers in animal genetics have isolated a small number, probably less than 50, putative causative variants for traits relevant to livestock breeding (reviewed for example by [1,2,3]). The variants and the evidence that support them are documented in a somewhat ad hoc fashion in scientific papers and databases

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