Refining selection signals in dairy sheep using high-density genotyping data

We previously identified broad candidate regions under selection in three ecotypes (plain, hill, and mountain) of Sarda and Valle del Belice sheep across altitudinal gradients using medium-density SNP chips. Here, we employed high-density genotyping data from independent animals to validate and refine these regions, focusing on adaptive signatures in the mountain ecotype. Joint analyses of the three ecotypes confirmed selection signals on chromosomes 19 and X in Sarda and on chromosome 3 in Valle del Belice. In Sarda, five genes were identified, including KDM6A, a key regulator of mammary function and stress response. In Valle del Belice, KCNA5 and KCNA6 (voltage-gated potassium channels) and GALNT8 (involved in glycosylation and immune regulation) emerged as candidates linked to cardiac and neuronal electrophysiology and health traits. We found little overlap between the candidate regions identified by the two approaches. Between-ecotype comparisons further confirmed and refined selection signals in the mountain ecotype, particularly on chromosome 3 in both breeds. We identified several missense, synonymous, and intronic variants within genes involved in the regulation of neuroendocrine, nervous, and cardiovascular systems, as well as immune response, respiratory efficiency, and musculoskeletal development, highlighting the multifaceted adaptations of the mountain ecotypes of both breeds to mountainous environments. Overall, our high-density analyses corroborate previous findings from the medium-density chip and, in several cases, refine the candidate regions detected. Although the specific genes under selection differ between the mountain ecotypes of Sarda and Valle del Belice sheep, they converge on similar biological pathways and functions, suggesting parallel adaptive mechanisms to high-altitude conditions.Regions of an animal's DNA can show signs of having been shaped by natural or human-driven selection. Over generations, sheep breeds living in different environments have adapted to local conditions, and this process has left detectable marks in their DNA. In this study, we compared three groups (plain, hill, and mountain) of Sarda and Valle del Belice sheep to understand how their genomes have changed in response to the environments. Using a more detailed genetic analysis than in our previous work, we confirmed and refined several DNA regions showing signs of adaptation, particularly in mountain sheep. We discovered genetic differences in the mountain groups of both breeds linked to muscle strength and to the regulation of hormonal, neural, cardiovascular, immune, and respiratory functions. These traits likely help mountain sheep remain strong, healthy, and productive in the cold, rugged, and pathogen-rich conditions typical of high-altitude environments. Although the specific genes differ between the two breeds, they influence similar biological functions, suggesting that both Sarda and Valle del Belice evolved similar strategies to thrive at high elevations.Comparative genomic analyses of three ecotypes from two dairy sheep breeds living across different altitudinal gradients revealed signatures of selection in genes associated with musculoskeletal development, cardiovascular and immune function, neuroendocrine regulation, and DNA repair. These biological pathways likely contribute to adaptation to high-elevation environments in the mountain ecotypes of both breeds.