The overall aim of this project is to improve equine health and welfare by identifying causative mutations for inherited diseases and performance traits to aid informed breeding of healthy horses. The project is a continuation and extension of my previous project SNIC 2021/5-129, and 2022/5-167. We use a comparative genomics approach, combining whole-genome sequencing (WGS) and bioinformatics with state-of-the-art clinical diagnosis of disease phenotypes. In the first part project a general framework for mutation-detection of equine monogenetic diseases was developed by WGS of two family trios (father-mother-offspring), and two family duos (mother-offspring). The initial focus are the diseases anophthalmia and microphthalmia, potentially autosomal recessive disease/s, recently observed among Swedish Warmblood horses. The objectives of this part of the study are to:
1. clinically define monogenic diseases with autosomal recessive inheritance (ongoing),
2. develop a general framework for identifying disease causing mutation with a bioinformatics pipeline for whole-genome sequencing (ongoing/nearly finished),
3. develop a plan for breeding advise in different scenarios of inheritance patterns, and severity of the disease (partly published/continuing).
This will be followed by further WGS of 20 horses to discover a potential genetic background of extreme joint laxity. We aim to confirm and validate association of putative genomic regions with highly flexible locomotion in horses, by genotyping, whole genome sequencing, and re-sequencing. We will pay special attention to chromosomal regions and genes known to be associated with hypermobility and connective tissue disorders in other species. In the planned study, we will describe the association between equine performance and phenotypes seen in collagen deficiencies and joint laxity syndromes. Identification of genetic markers or causative mutations in such regions could provide new tools in horse breeding to select for healthy, sustainable, and better performing horses.