Genome wide association study for longevity of dairy cows

The lifespan of a cow is an indicator of her health and fertility but is also essential for the profit of the dairy farmer. Genetic evaluations of length of productive life are routinely performed for most dairy cattle populations, using the infinitesimal model deriving information about the genotype of an animal from phenotypic information of itself and/or relatives. The heritability of functional longevity, corrected for voluntary culling, is about 0.15 in many dairy cattle populations, rendering the search for important genes for this trait feasible. A procedure consisting of two steps is considered to fine-map regions responsible for longevity of cows in Fleckvieh (dual purpose Simmental) and Brown Swiss cattle. In the first step, a population wide association study will be performed for functional longevity and a range of related traits. Genotypes of 54.000 SNP (single nucleotide polymorphism) markers of 2500 progeny tested Fleckvieh and 1000 Brown Swiss bulls are available to the project. Testing for association will be performed for single SNPs utilizing case-control methods like logistic regression and score tests. A mixed model approach which accounts for multiple levels of relatedness and haplotype based analyses will also be applied. The second stage is a case-control study to be applied on samples of 600 Brown Swiss and Fleckvieh cows each. Cases will be cows with extreme phenotypes, choosing 300 among the 500 oldest currently living cows in populations of 260,000 Fleckvieh and 60,000 Brown Swiss cows. Statistical analysis of the data will be carried out with multi-SNP analyses and haplotype based analyses. In addition, allelotyping of pooled DNA will be performed to validate that approach for future mapping exercises of diseases routinely recorded in the Austrian cattle health monitoring system.

The lifespan of a cow is an indicator of her health and fertility but is also essential for the profit of the dairy farmer. Genetic evaluations of length of productive life are routinely performed for most dairy cattle populations, using the infinitesimal model deriving information about the genotype of an animal from phenotypic information of itself and/or relatives. The heritability of functional longevity, corrected for voluntary culling, is about 0.15 in many dairy cattle populations, rendering the search for important genes for this trait feasible.In the current project we have explored genotypes of ~6000 bulls from the entire German-Austrian Fleckvieh population in order to find region connected to and thus potentially harbouring genes for longevity. Each bull was genotyped for 54,000 single nucleotide polymorphism (SNP) markers. We used the so called genome wide association studies (GWAS) to evaluate the effect of each SNP.There are many different methodologies to perform GWAS on a given data set, with differing performance and ability to predict significant markers and corresponding genome regions. The challenge was to distinguish between true positive and false positive result, with a minimum number of false negative SNPs. In order to test the hypotheses several rounds of simulation studies were conducted with increasing complexity of relationships between the markers. Since there is a better understanding of the true associations in the simulations, the different methodologies could be tested for correctness. In a follow up step the best methods should be used to detect genomic associations of interest in real data sets.