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Runs of Homozygosity Reveal Signatures of Positive Selection for Reproduction Traits in Breed and Non-Breed Horses

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Runs of Homozygosity Reveal Signatures of Positive Selection for Reproduction Traits in Breed and Non-Breed Horses

Julia Metzger et al. BMC Genomics.

Abstract

Background: Modern horses represent heterogeneous populations specifically selected for appearance and performance. Genomic regions under high selective pressure show characteristic runs of homozygosity (ROH) which represent a low genetic diversity. This study aims at detecting the number and functional distribution of ROHs in different horse populations using next generation sequencing data.

Methods: Next generation sequencing was performed for two Sorraia, one Dülmen Horse, one Arabian, one Saxon-Thuringian Heavy Warmblood, one Thoroughbred and four Hanoverian. After quality control reads were mapped to the reference genome EquCab2.70. ROH detection was performed using PLINK, version 1.07 for a trimmed dataset with 11,325,777 SNPs and a mean read depth of 12. Stretches with homozygous genotypes of >40 kb as well as >400 kb were defined as ROHs. SNPs within consensus ROHs were tested for neutrality. Functional classification was done for genes annotated within ROHs using PANTHER gene list analysis and functional variants were tested for their distribution among breed or non-breed groups.

Results: ROH detection was performed using whole genome sequences of ten horses of six populations representing various breed types and non-breed horses. In total, an average number of 3492 ROHs were detected in windows of a minimum of 50 consecutive homozygous SNPs and an average number of 292 ROHs in windows of 500 consecutive homozygous SNPs. Functional analyses of private ROHs in each horse revealed a high frequency of genes affecting cellular, metabolic, developmental, immune system and reproduction processes. In non-breed horses, 198 ROHs in 50-SNP windows and seven ROHs in 500-SNP windows showed an enrichment of genes involved in reproduction, embryonic development, energy metabolism, muscle and cardiac development whereas all seven breed horses revealed only three common ROHs in 50-SNP windows harboring the fertility-related gene YES1. In the Hanoverian, a total of 18 private ROHs could be shown to be located in the region of genes potentially involved in neurologic control, signaling, glycogen balance and reproduction. Comparative analysis of homozygous stretches common in all ten horses displayed three ROHs which were all located in the region of KITLG, the ligand of KIT known to be involved in melanogenesis, haematopoiesis and gametogenesis.

Conclusions: The results of this study give a comprehensive insight into the frequency and number of ROHs in various horses and their potential influence on population diversity and selection pressures. Comparisons of breed and non-breed horses suggest a significant artificial as well as natural selection pressure on reproduction performance in all types of horse populations.

Figures

Fig. 1
Fig. 1
Number and size of runs of homozygosity (ROH) detected in ten horses. The length of ROHs was categorized into small, medium and large ROH regions. The results of plink analysis with windows of minimum amount of 50 homozygous SNPs (a) and 500 homozygous SNPs (b) are shown
Fig. 2
Fig. 2
GeneMANIA network of six genes in ROH regions shared by the Hanoverian. The genes of interest are represented as black circles, related genes as grey circles. Genetic interactions are displayed as green lines and co-expressions as violet lines. All six genes are interrelated with each other
Fig. 3
Fig. 3
GeneMANIA network of 139 genes in 50-SNP window ROH regions shared by non-breed horses. The genes of interest are represented as black circles, related genes as grey circles. Genetic interactions are displayed as light green lines, predicted related genes as orange lines, physical interactions as red lines, co-localization as blue lines, shared protein domains as dark green lines and co-expressions as violet lines
Fig. 4
Fig. 4
GeneMANIA network of 7 genes in 500-SNP window ROH regions shared by non-breed horses. The genes of interest are represented as black circles, related genes as grey circles. Predicted related genes are displayed as orange lines, physical interactions as red lines, co-localization as blue lines, shared protein domains as dark green lines and co-expressions as violet lines
Fig. 5
Fig. 5
Tajima’s D estimate on equine chromosome 28 in the region of 13.68–15.75 Mb for all ten horses. Decreased Tajima’s D values below −1.2 can be observed in the consensus ROH extending over 14.65–14.78 Mb and harboring KITLG

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