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

## TL;DR

This study uses high-density genotyping to refine genetic selection signals in mountain-dwelling dairy sheep breeds, identifying genes linked to adaptation to high-altitude environments.

## Contribution

The study refines and validates selection signals using high-density data, revealing breed-specific genes and shared adaptive pathways in mountain ecotypes of Sarda and Valle del Belice sheep.

## Key findings

- Selection signals on chromosomes 19 and X in Sarda and chromosome 3 in Valle del Belice were confirmed and refined.
- Genes like KDM6A, KCNA5, KCNA6, and GALNT8 were identified as candidates linked to health and adaptation traits.
- Candidate regions showed little overlap between breeds but converged on similar biological pathways like cardiovascular and immune functions.

## Abstract

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.

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.