Whole-genome resequencing of the Kazakh coarse-wool fat-tailed sheep identifies functional variants in disease-associated genes

Abstract

The Kazakh coarse-wool fat-tailed sheep is an indigenous breed of Central Asia and represents a valuable genetic resource adapted to harsh continental environmental conditions. Despite its economic importance, its genomic architecture, population structure, and the genetic basis of disease resistance remain largely unexplored. Whole-genome sequencing was performed on 20 Kazakh coarse-wool fat-tailed sheep using the Illumina NovaSeq 6000 platform. Population structure was assessed by principal component analysis (PCA) using comparative genomic data from six domestic sheep breeds and the wild ancestor Ovis orientalis . Selection signatures were identified by integrating FST, nucleotide diversity ( π ), and Tajima’s D statistics. Variants within the PRNP and TMEM154 loci were extracted from the filtered VCF files using bcftools. PCA revealed a distinct genetic cluster of the Kazakh coarse-wool fat-tailed sheep, showing close genetic affinity to Bashibai and Hu sheep while remaining clearly differentiated from European meat and short-tailed breeds. A total of 208 candidate selective sweep regions containing 297 overlapping genes were identified. Quantitative trait loci (QTL) annotation revealed enrichment for loci associated with resistance to gastrointestinal nematodes (14 QTLs), body weight (9 QTLs), susceptibility to pneumonia (2 QTLs), clinical mastitis (2 QTLs), and susceptibility to Mycobacterium avium subsp. paratuberculosis infection (2 QTLs). Five PRNP haplotypes were identified, with 60% of animals classified as high-risk (NSP3) for scrapie susceptibility. No animals carrying the fully resistant ARR/ARR genotype were detected. At the TMEM154 locus, 95% of individuals carried the E35E genotype, which is associated with increased genetic susceptibility to Maedi-Visna. This study provides the first comprehensive genomic characterization of the Kazakh coarse-wool fat-tailed sheep, revealing its unique population structure, genomic regions under selection associated with adaptation and disease resistance, as well as genetic predisposition susceptibility-associated genotypes for scrapie and Maedi-Visna. These findings provide a valuable genomic resource for marker-assisted breeding, genetic improvement, and conservation of indigenous sheep genetic resources in Kazakhstan.