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Detection and selection against early embryonic lethals in US beef breeds
More than 3,000 bovine genomes have now been sequenced worldwide and much of the variation within the genome of cattle has been discovered. Many variants likely to have functional effects due to their locations within annotated coding regions have been identified. However, the lack of complete annotation leads to our inability to identify variants that lie within regulatory regions and furthermore, the phenotypic effects caused by coding variants are not well understood. Among these are the class of loss of function variants within genes that are essential for life – a gene set that is largely conserved in identity among mammals. Based upon marker haplotype analyses performed primarily in dairy breeds, we postulate that several lethal variants segregate within most cattle breeds and that these variants tend to be breed specific in their identity. To identify these variants, we have designed the first generation of a bovine functional assay, the GGP-F250, to contain 34K common variants present on many of the genotyping assays currently used by the cattle industry and 199K predicted genic functional variants. The assay is publicly available from GeneSeek. These variants were discovered by analyzing whole genome sequence data for 297 cattle from 17 breeds and RNA-seq data for 159 animals and were confirmed using data from the 1000 Bull Genomes Project and dbSNP. We have genotyped 18,300 animals with this assay representing Holstein and 9 US beef breeds including over 11,000 Angus animals and these data are being used to fine map QTL underlying susceptibility to respiratory disease and feed efficiency. Data from Angus are being used to sequentially test each putative functional variant for a deficiency of homozygotes and fully penetrant lethals will manifest with a complete lack of homozygotes. Candidate lethal alleles will be migrated to commonly utilized assays used in the beef industry such as the GGP-LD and GGP-HD platforms to genotype hundreds of thousands of animals and validate the lack of homozygotes. Mate selection software is being developed as part of the USDA NIFA grant #2013-68004-20364 “Identification and management of alleles impairing heifer fertility while optimizing genetic gain in Angus cattle” project to assist breeders with mating decisions based on each animal’s carrier status for defects and embryonic lethals.
Keywords: GGP-F250, Fertility, Embryonic lethal