Genome-wide scans for the detection of genetic variants associated with reproductive performance in dogs

Author(s)

Rafaela Beatriz Pintor Torrecilha

• Document type: Doctoral Thesis
• Press: Jaboticabal. 2018-12-05.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências Agrárias e Veterinárias. Jaboticabal
• Defense date: 2018-10-25
• Advisor: José Fernando Garcia

Abstract

Functional variant (FV) is a DNA sequence polymorphism that has effects on the function or even the level of expression of one or more genes. FVs are frequent targets of negative or positive selection in a population due to its high probability of interfering in cell, tissue or system phenotypes. Some FVs may even cause partial or total loss of gene function, in which case they are called loss-of-function variants (LoFVs). Domestic dogs (Canis lupus familiaris) have low genetic variability resulting from intense human-driven artificial selection for extreme phenotypes of morphological and behavioral traits. High levels of inbreeding in canine populations favor the intensification of genetic drift and, consequently, an increase in the prevalence of FVs and LoFVs that would be maintained at low frequencies if these populations presented higher genetic variability. Thus, the domestic dog is a valuable model for studying physiological processes and human genetic diseases. The recent emergence of tools for genomic analysis has assisted in the identification of FVs and LoFVs of zootechnical and biomedical interest in dogs. These variants can be mapped through two distinct but complementary genomic scanning strategies. The first, known as Genome-Wide Association Study (GWAS), involves testing of phenotype-genotype associations. The second consists in the search for allelic combinations, called haplotypes, that occur in high frequency, but that present deficiency of homozygosity. In the present work, we used both strategies in the mapping of FVs and LoFVs of high functional impact associated with reproduction in dogs. In the first study, a GWAS for average litter size was conducted in Entlebucher Mountain dogs, which revealed a FV in the growth differentiation factor 9 gene (GDF9). In the second study, we reported high frequency haplotypes with deficiency of homozygosity in the Chinese Crested, Entlebucher Mountain, Labrador Retriever and Golden Retriever dog breeds. Both approaches allowed the identification of variants that may be associated with reproductive performance. (AU)

• FAPESP's process: 17/08373-1 - Detection of deleterious alleles through absence of homozygous haplotypes in dogs
• Grantee: Rafaela Beatriz Pintor Torrecilha
• Support Opportunities: Scholarships in Brazil - Doctorate