Single-Locus and Multi-Locus Genome-Wide Association Studies Identify Genes Associated with Liver Cu Concentration in Merinoland Sheep.

Economic losses due to copper intoxication or deficiency is a problem encountered by sheep farmers. The aim of this study was to investigate the ovine genome for genomic regions and candidate genes responsible for variability in liver copper concentration. Liver samples were collected from slaughtered lambs of the Merinoland breed from two farms, and used for measurement of copper concentration and genome-wide association study (GWAS). A total of 45,511 SNPs and 130 samples were finally used for analysis, in which single-locus and several multi-locus GWAS (SL-GWAS; ML-GWAS) methods were employed. Gene enrichment analysis was performed for identified candidate genes to detect gene ontology (GO) terms significantly associated with hepatic copper levels. The SL-GWAS and a minimum of two ML-GWAS identified two and thirteen significant SNPs, respectively. Within genomic regions surrounding identified SNPs, we observed nine promising candidate genes such as DYNC1I2, VPS35, SLC38A9 and CHMP1A. GO terms such as lysosomal membrane, mitochondrial inner membrane and sodium:proton antiporter activity were significantly enriched. Genes involved in these identified GO terms mediate multivesicular body (MVB) fusion with lysosome for degradation and control mitochondrial membrane permeability. This reveals the polygenic status of this trait and candidate genes for further studies on breeding for copper tolerance in sheep.

Capturing Genetic Diversity and Selection Signatures of the Endangered Kosovar Balusha Sheep Breed.

There is a growing concern about the loss of animal genetic resources. The aim of this study was to analyze the genetic diversity and potential peculiarity of the endangered Kosovar sheep breed Balusha. For this purpose, a dataset consisting of medium-density SNP chip genotypes (39,879 SNPs) from 45 Balusha sheep was generated and compared with SNP chip genotypes from 29 individuals of a second Kosovar breed, Bardhoka. Publicly available SNP genotypes from 39 individuals of the relatively closely located sheep breeds Istrian Pramenka and Ruda were additionally included in the analyses. Analysis of heterozygosity, allelic richness and effective population size was used to assess the genetic diversity. Inbreeding was evaluated using two different methods (FIS, FROH). The standardized FST (di) and cross-population extended haplotype homozygosity (XPEHH) methods were used to detect signatures of selection. We observed the lowest heterozygosity (HO = 0.351) and effective population size (Ne5 = 25, Ne50 = 228) for the Balusha breed. The mean allelic richness levels (1.780-1.876) across all analyzed breeds were similar and also comparable with those in worldwide breeds. FROH estimates (0.023-0.077) were highest for the Balusha population, although evidence of decreased inbreeding was observed in FIS results for the Balusha breed. Two Gene Ontology (GO) TERMs were strongly enriched for Balusha, and involved genes belonging to the melanogenesis and T cell receptor signaling pathways, respectively. This could result from selection for the special coat color pattern of Balusha (black head) and resistance to certain infectious diseases. The analyzed diversity parameters highlight the urgency to preserve the local Kosovar Balusha sheep as it is clearly distinguished from other sheep of Southeastern Europe, has the lowest diversity level and may harbor valuable genetic variants, e.g., for resistance to infectious diseases.