Kerstin Lindblad-Toh research group

Comparative Genetics and Genomics

The overall research focus is to identify genes and mutations of relevance for canine and human disease. Two strategies are utilized together to accomplish this. Using comparative genomics, we identify functional elements in the human and mammalian genomes and study their evolution and importance for disease. Using comparative genetics, we study dogs to find disease mutations, genes and disease pathways and then translate these findings to human patients.

The comparative genomics work encompass the Zoonomia project which is part of an ongoing collaboration with colleagues at the Broad Institute and across the world to find functional elements in the human genome and as well as in mammals. In 2023 we published 11 papers in Science based on our Zoonomia project. As part of the project, we sequenced, aligned and analyzed 240 mammalian genomes. With this data we can determine if positions in the genome are functional at single base resolution. For both transcribed and regulatory elements we study the evolutionary changes seen among species, and of particular interest is when these changes can be coupled to adaptation/selection. The Zoonomia data set is also being used to identify which mutations are likely to underly diseases including amyotrophic lateral sclerosis (ALS), psychiatric diagnoses like Obsessive Compulsive Disorder (OCD), and multiple cancers.

The unique breeding history of the domestic dog offers an unparalleled opportunity to map genes important in disease susceptibility, morphology, and behaviour. The breed structure of the dog has resulted in certain genetic risk factors being enriched within specific populations and recent bottlenecks have generated long haplotypes. Together this makes the dog excellent for trait mapping. The dog is also a unique animal to use for comparative analysis since dogs spontaneously develop similar diseases as humans, they share largely the same environment and have roughly the same gene content. The research group has been able to map genes for both monogenic and complex traits including white coat colour, ALS, OCD, several cancers and Systemic Lupus Erythematous (SLE). For several diseases, including immunological diseases, we have identified strong candidate loci in dogs and have performed targeted resequencing in human patients with immunological disease to find genes associated with the corresponding human disease.

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