Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds

Abstract

BackgroundTo date, genome-scale analyses in the domestic horse have been limited by suboptimal single nucleotide polymorphism (SNP) density and uneven genomic coverage of the current SNP genotyping arrays. The recent availability of whole genome sequences has created the opportunity to develop a next generation, high-density equine SNP array.ResultsUsing whole genome sequence from 153 individuals representing 24 distinct breeds collated by the equine genomics community, we cataloged over 23 million de novo discovered genetic variants. Leveraging genotype data from individuals with both whole genome sequence, and genotypes from lower-density, legacy SNP arrays, a subset of ~5 million high-quality, high-density array candidate SNPs were selected based on breed representation and uniform spacing across the genome. Considering probe design recommendations from a commercial vendor (Affymetrix, now Thermo Fisher Scientific) a set of ~2 million SNPs were selected for a next-generation high-density SNP chip (MNEc2M). Genotype data were generated using the MNEc2M array from a cohort of 332 horses from 20 breeds and a lower-density array, consisting of ~670 thousand SNPs (MNEc670k), was designed for genotype imputation.ConclusionsHere, we document the steps taken to design both the MNEc2M and MNEc670k arrays, report genomic and technical properties of these genotyping platforms, and demonstrate the imputation capabilities of these tools for the domestic horse.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3943-8) contains supplementary material, which is available to authorized users.

Robust remapping of equine SNP array coordinates to EquCab3

“…Three commercial SNP genotyping arrays have been made available for the horse to date: Illumina Equine SNP50, 1 SNP70 BeadChips (SNP50 and SNP70) and the Thermo‐Fischer (formerly Affymetrix) Axiom ® MNEc670k array (MNEc670k), designed for imputation to two million SNPs on the Axiom ® MNEc2M test array 2 . For the development of all these arrays, EquCab2 3 served as the reference genome.…”

Equine recombination map updated to EquCab3.0

“…Coat and skin color dilution phenotypes caused by variants in SLC45A2 are documented in multiple vertebrate species. [1][2][3][4] In equines, mutations in the SLC45A2 gene, located on chromosome 21, are responsible for the cream, pearl and sunshine dilutions. 5,6 In this study, we focused on a Gypsy breed mare that appeared phenotypically cremello (light creamy white) but tested negative for any known dilution or spotting alleles, including sabino, W20, tobiano, PATN1 and SW1-4 ( Fig.…”

“…Our dataset consists of previously generated SNP genotypes of 485 horses from 32 breeds. 2 Genomic coordinates for these data were originally based on the EquCab2 reference build 3 ; therefore, we performed probe-based remapping to EquCab3, 5 producing a final set of 1 820 349 biallelic SNP genotypes, which we phased using BEAGLE. 6 We generated recombination maps as described previously.…”

Ruling out BGN variants as simple X‐linked causative mutations for bilateral corneal stromal loss in Friesian horses

“…It is hypothesized that the disorders seen in Friesians may represent a multisystem manifestation of improper collagen formation . Two such disorders have had causal variants reported: dwarfism ( B4GALT7: c.50G>A) and hydrocephalus ( B3GALNT2: c.1423C>T). Neither variant was found to be concordant with BCSL ( P = 1.0, P = 0.53 respectively; Tables & ), thus these variants can be ruled out as digenic contributors to BCSL.…”