Runs of homozygosity in Italian Holstein bulls: a permutation approach and time-based mapping of the genomic regions potentially under selection

Abstract

Background: Runs of homozygosity (ROH) occurrence in animal genomes may result from a high level of relatedness within the population or from positive selection. ROH investigation enables the assessment of the degree of individual autozygosity at the genome-wide level, providing insights into genetic background and development history of a population. In this context, the main objectives of this study were to: 1) develop a method based on permutation tests for detecting single nucleotide polymorphisms (SNP) significantly included in ROH genomic regions of Italian Holstein bulls; 2) identify candidate genes close to the SNP frequently positioned within ROH; 3) investigate the effects of genetic selection on ROH distribution and ROH islands; and 4) assess potential associations between ROH and economically important traits in Italian Holstein cattle. We used high-density SNP data of 3,009 Italian Holstein bulls for identifying ROH regions. The threshold for declaring a SNP as significantly included in a ROH region was obtained by randomly shuffling SNP within animals for each chromosome. The chromosome-wide threshold was the 99th percentile of the distribution of the number of times a SNP was included in a ROH segment (SNPROH) for a specific chromosome. To investigate the influence of ROH on relevant traits, a genome-wide association study testing the presence/absence of specific ROH and a mixed model to quantify the effect of ROH-based inbreeding were carried out. Results: The top 24,905 significant SNP were distributed on ten chromosomes, in genomic regions known to harbor genes involved in milk traits. One region on BTA20 exhibited an interesting pattern of SNPROH occurrence across animals grouped according to the year of birth, underlining an intense selection pressure in this genomic region. The analyses on the relationship between ROH and pseudo-phenotypes for various traits showed a significant influence of inbreeding on milk and protein yields, and a fertility aggregate index, with the presence/absence of 14 ROH regions having a significant effect on different traits (milk, fat, and protein yields; fat percentage; and somatic cell score). Conclusions: The application of permutation to a high-density (HD) SNP chip data enabled the identification of genomic regions with high levels of homozygosity in Italian Holstein bulls and revealed associations between ROH occurrence and economically important traits in the studied population.