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Mutation and Recombination in the Cattle Germline: Genomic Analysis and Impact on Fertility

Final Report Summary - DAMONA (Mutation and Recombination in the Cattle Germline: Genomic Analysis and Impact on Fertility)

The DAMONA project aimed at studying the fundamental biological process of recombination and de novo mutation (DNM) in the germ line of the cow, an economically important livestock species. DAMONA has and continues to deliver in both fundamental and applied science. Among the most striking scientific discoveries of the project is the realization that the very first cell divisions during embryonic development are particularly prone to mutation. As a result, individuals are mosaic for a much higher proportion of DNM than previously assumed. This could, if it translates to human, have a major impact on the risk for siblings of patients having inherited pathogenic DNMs. DAMONA has identified tens of embryonic lethal (EL) mutations that are negatively impacting fertility in cattle and this information can now be used by breeders to avoid at-risk matings between parents carrying the same EL. DAMONA has identified thousands of disruptive coding mutations which have already been genotyped in tens of thousands of animals. The impact of this information on the accuracy of "genomic selection" (the routine use of DNA diagnostics to identify the genetically superior parents for the next generation) is presently being evaluated. Finally, advances accrued through DAMONA, and information provided by the DAMONA dataset (whole genome sequence information from 750 animals), have allowed the development of a novel method for the identification of cows with subclinical mastitis by shallow whole genome sequencing of DNA extracted from the farm's milk tank, and this method is presently being deployed in the field.