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New Animal Genetics Papers Highlight Use of Illumina's SNP Chips to Study Horse Genetics

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A pair of studies that used Illumina's EquineSNP50 BeadChip to investigate inbreeding in Thoroughbred horses and SNP misplacement in the horse genome map has been published in the June issue of Animal Genetics.

In the first study, a team at the Roslin Institute and the UK's Animal Health Trust relied on the EquineSNP50, which includes about 55,000 SNPs distributed across the equine genome, to identify SNPs that may have been incorrectly positioned on the map of the horse genome.

Laura Corbin, a researcher at the Roslin Institute and the lead author on the second study, told BioArray News that SNP misplacement is significant because sequence errors that lead to SNPs being given the wrong position can impact genomic analyses that rely on SNP order, such as homozygosity mapping and haplotyping.

According to the paper, the authors used linkage disequilibrium to identify SNPs on the EquineSNP50 BeadChip that may be incorrectly positioned on the genome map. A total of 1,201 Thoroughbred horses were genotyped using the EquineSNP50 BeadChip and LD was evaluated in a pairwise fashion between all autosomal SNPs, both within and across chromosomes. Filters were then applied to the data, first to identify SNPs that may have been mapped to the wrong chromosome and then to identify SNPs that may have been incorrectly positioned within chromosomes.

The authors identified a single SNP on ECA28, which showed low LD with neighboring SNPs but "considerable LD" with a group of SNPs on ECA10. Additionally, a cluster of SNPs on ECA5 showed "unusually low LD" with surrounding SNPs. In total, 39 SNPs met the criteria for unusual "within-chromosome LD," leading the authors to conclude that some SNPs may be misplaced.

Corbin said that her team's approach can "help to identify regions of the genome [that] should be prioritized for re-sequencing work in the future." The ability to prioritize regions in this way is "particularly important in species such as the horse where resources are somewhat limited," she added.

SNP arrays have been "particularly useful" to Corbin's research because with horses it is "challenging to find sufficiently large families to conduct the more traditional linkage type studies used for [quantitative loci mapping]," she said. "The dense SNP data obtainable from chips in livestock has also been a major driver behind the potential of genomic selection, which is now used in cattle," Corbin added.

Illumina in March 2011 began offering a higher-density SNP array for horse studies called the EquineSNP70 (BAN 2/1/2011).

Of the higher-density array, Corbin said that she is "always interested in having more data to do our analyses," but said it is "difficult to know at this stage whether denser chips are the way forward or whether sequencing will simply replace genotyping chips in the future."

Inbred Thoroughbreds

In the second study, a group of researchers from horse-genetics firm Equine Analysis, the University of Kentucky, and the UK's Royal Veterinary College used the EquineSNP50 to uncover significant inbreeding in thoroughbreds, especially during the past 15 years, a trend that the authors called "worrisome."

The researchers genotyped 467 Thoroughbred horses born between 1961 and 2006 using the EquineSNP50. They determined that inbreeding in Thoroughbreds has increased over the past 40 years, with the majority of the increase in inbreeding found in cohorts born in 1996 and after, which, the authors note, coincides with the introduction of stallions covering larger numbers of mares.

According to the paper, all Thoroughbred horses that are alive today, estimated to number in the millions, are descended from three stallions and about 70 mares that were bred in England in the early 18th century. At the same time, breeding practices have evolved with the Thoroughbred horse over the past 50 years, as an emphasis changed from breeding "superior race horses" to siring as many foals as possible to sell, the authors wrote. They noted that 40 years ago, most stallions "covered," or were mated with, a maximum of 40 mares a year, while many current stallions cover close to 200 mares. Breeding methods have changed too, with companies like Midway, Ky.-based Equine Analysis now offering genetic tests to identify animals that will race well.

The result of this shift toward breeding more animals from popular stallions has resulted in a decrease of genetic diversity, according to the authors, much of it taking place during the last decade, as the popular stallions covered more and more mares.

"It is worrisome that the increase in inbreeding that we observe is therefore not spread over a 40-year period but is concentrated in the period following the dramatic changes made to breeding practices in the mid-1990s," the authors wrote. While they argued that the loss of genetic diversity identified in this study is not "excessive," they said the trend is "worrisome." The Thoroughbred industry "should not be complacent" and "continued monitoring of the situation is needed to ensure that recent major changes in breeding methods do not further negatively impact on this historic breed," the authors wrote.

BioArray News was unable to reach the paper's authors for comment.

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