Application of genome-wide single-nucleotide polymorphism arrays to understanding dog disease and evolution.

Abstract

The generation of vast SNP repertoires from genome sequencing projects together with rapid improvements in large-scale SNP genotyping allowed the development of high-density genome-wide SNP microarrays in many animal species. This thesis presents two examples of the application of SNP arrays to understanding disease and evolution in the dog, whose evolutionary history makes it a suitable animal model for trait mapping and a fascinating case of artificial selection._x000D_ In the first example, motivated by the fact that only a certain proportion of individuals infected with Leishmania are susceptible to develop clinical leishmaniasis disease we tried to dissect how and to what extent host genetics determines whether infected individuals progress to clinical disease. Firstly, we tried to map loci affecting the phenotype and for the strongest associations we tested whether their haplotype structure correlated with the affection status and examined their nearby genetic content. Secondly, we estimated the heritability of the trait and assessed the capability to predict the phenotype from genomic information._x000D_ In the second case, we searched for genomic footprints of selection in the Boxer breed. We presented a novel selective sweep of >8 Mb on chromosome 26. Hinted by the presence of another selective sweep on chromosome 1 previously associated with canine brachycephaly, characterized by severe shortening of the muzzle and a breed-defining trait of the Boxer, we investigated on the relationship between the selective sweep on chromosome 26 and this trait. We tried to prove the selective sweep is representative of the Boxer breed and that it is also present in other brachycephalic breeds but absent in non-brachycephalic breeds and wolf. Finally, we examined the genetic content of the selective sweep to find putative targets of selection and potential undesired health consequences for the breeds bearing the phenotype.

Date of Award	20 Sept 2012
Original language	English
Supervisor	Olga Francino Martí (Director) & Laura Altet Sanahujes (Director)