The overall aim of this project is to improve animal performance, health and welfare by identifying causative mutations for inherited diseases and performance traits to aid informed breeding of healthy animals. Primarily, the project focus on the species horse, cat, and moose, but other species could as well be included. We use a comparative genomics approach, combining Whole Genome Sequencing (WGS) and bioinformatics with state-of-the-art clinical diagnosis of disease phenotypes. The objectives of this on-going study are to: 1. clinically define animal diseases with various inheritance patterns, 2. further develop our general framework for identifying disease causing mutation with a bioinformatics pipeline for whole-genome sequencing, 3. integrate bioinformatics and machine learning to evaluate the produced genomic data with inheritance patterns, and clinical genetics 4. develop a plan for breeding advise in different scenarios of inheritance patterns, and severity of the disease. In the first part of the project a general framework for mutation-detection of equine monogenetic diseases was developed by WGS of family trios. This bioinformatic pipeline is up and running for variant calling of SNVs, indels, and larger structural variants. The called variants are further analyzed for different inheritance patterns. The family trio WGS will be extended with more families, and control samples. Other projects will involve WGS of cases and controls to discover causative variants for diseases, and other traits. The initial focus was on anophthalmia and microphthalmia, recently observed among Swedish Warmblood horses. Another project in horses deals with hypermobility syndromes. There are also projects to find causative variants for thoracic malformation I Bengal cats, and the white coat color of moose. Identification of genetic markers or causative variants could provide new tools in animal breeding to select for healthy, sustainable, and better performing horses. In the case of moose, our future results could be a tool for hunting management.