Jämförande genetik och genomik för att förstå humana komplexa sjukdomar.

Tidsperiod: 2014-07-01 till 2023-12-31

Projektledare: Kerstin Lindblad-Toh

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 50 000 000 SEK

The domestic dog encompasses hundreds of genetically isolated breeds, many of which have increased risk of specific diseases. With mapping tools available, we are in a unique position to map canine disease genes to learn about human biology and medicine. The genetic homogeneity within dog breeds yields a cleaner picture of disease risk and greater ease at finding these risk factors. To date, we have identified >40 associated loci for >10 complex traits. For several diseases we find different genes and pathways predisposing to the disease in each breed. The major aim of this project is to continue to dissect the genetic components of important complex diseases in dog breeds and to utilize this information to understand and dissect the genetics of human diseases. Aim 1: Identification and functional analysis of canine disease genes and pathways. GWAS will be performed in several cancers, immunological disease and neuropsychiatric disorders. Functional analysis of candidate mutations utilizes comparative genomics, RNASeq and diverse functional assays. Aim 2: Identification of human disease genes based on canine disease genes and pathways. We will perform targeted resequencing of genes and regulatory elements in human disease cohorts, based on our canine findings. Aim 3: Piloting canine personalized treatment strategies based on inherited risk factors. We aim to pilot personalized treatment by linking outcome to inherited risk factors in dogs and then translate to human patients.