Grant: Discovery Grants Program - Individual

The North Atlantic right whale is one of the most endangered large whales in the world, numbering about 500 individuals. Unlike other protected whale species it is not recovering due to a combination of anthropogenic-caused mortalities and a very poor reproductive rate. There is evidence that part of the reproductive problem is fertility issues both in males and females including loss of pregnancies at various stages leading to females with fewer calves and longer inter-calf intervals. One of its closest terrestrial relatives is the cow and dairy cow breeds, like Holsteins, are currently experiencing a comparable crisis in reproduction, due to long-term selection for high milk production. As a result of the sequencing of the bovine genome there have been many large scale genetic association studies of single nucleotide polymorphisms (SNPs) with fertility traits mainly in cows but more recently in bulls. This had led to the identification of a large number of candidate genes and genomic regions (industry selected chromosomal haplotypes) and variants that are associated with fertility traits. The different haplotypes, identified in various breeds, are associated with pregnancy loss at different stages and these occur at different frequencies. The ability in bovines to perform large-scale analyses of well-characterised animals and assess stages of reproductive failure through semen evaluation, in vitro fertilization, embryo splitting, pregnancy loss and transplantation has allowed identification of candidate genes and variants that could not have been uncovered in a natural population (eg STAT 5A, STAT 5B, FGF2, PGR1, DPR, ITGB5, GHR,FSHR, IGF1,NLPR9, LEP, HSPA1, PAPPa2, POU1F1, MAP1B, PPP1, Stat 5AR11, LOC784935, CACNA1H, LOC617302, LOC 521021, CATsper). I have received funding to sequence the North Atlantic right whale genome in collaboration with the Broad Institute and propose a comparative genomics approach of the North Atlantic right whale, the southern right whale and the cow together with other mammalian species to identify variants at candidate loci contributing to the reproductive problems. 2014 has been declared the international year of the right whale and this species will represent the first large whale genome sequenced. My laboratory holds the North Atlantic right whale DNA and tissue bank of over 1100 samples for 600 individuals and this represents over 75% of the current species and the genetic data-base contains genotype profiles at 35 microsatellite loci, the mitochondrial control region sequence and genotypes at MHC I and II loci (http://narightwhale.nrdpfc.ca/ ). The long-term field study of the species coordinated through the New England Aquarium and the photo-identification catalogue (DIGITS) has allowed identification of most calves born and their mothers for the past 25 years. This provides information on calving rates, calving intervals and nulliparous females. Recently we were able to identify the putative mating ground as the Great South Channel using the data-base. It has also allowed the assignment of about 150 paternities, providing information on males with multiple paternities and males with no paternities. I will compare the North Atlantic and southern right whales genomes with that of the cow and assess the variants present at the candidate fertility loci. All individuals represented in the DNA bank will be genotype at informative SNPs. I will correlate genotypes and alleles of whales with respect to reproductive performance to understand the molecular basis for the reproductive dysfunction. This genomic and candidate gene analysis will form the molecular foundation for the species as it deals with major oceanographic and food distribution changes resulting from climate change.