Selecting functional alleles in purebred and composite beef cattle

Authors: Snelling, Warren; McDaneld, Tara; BENNETT, GARY - Retired ARS Employee; Kuehn, Larry

Submitted to: World Congress of Genetics Applied in Livestock Production
Publication Type: Abstract Only
Publication Acceptance Date: 5/8/2026
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Genetic load is caused by deleterious alleles, and alleles causing loss of gene function are generally deleterious. After observing variation in the number of loss-of-function (LOF) alleles carried by individuals with whole genome sequence (WGS), an experiment to manipulate LOF counts by selection was initiated with the idea that reducing LOF alleles would reduce genetic load and increase fitness. Selection was applied to four beef cattle populations, three composites and purebred Angus. The composites beginning the selecting functional alleles (SFA) project were ¼ British (B) x ¾ Continental (C) breeds (MARC I), ½ B x ½ C (MARC II), and ¾ B x ¼ C (MARC III). In the fall of 2016, pregnant females and available bulls were split between select and control lines within each population according to genotypes for LOF variants. Subsequently, replacement heifers and bulls have been selected from within each line; select line calves with the lowest LOF counts are retained, as are random control line calves. Genotypes were initially obtained for LOF variants probed by the GGP-F250 assay, which was designed to contain functional variants in annotated protein-coding sequence that were known at the time. Beginning In 2020, LOF genotypes have been imputed from low-coverage WGS (~0.5X) with a reference panel of >900 individuals representing major dairy and beef breeds and crosses. Sires from the SFA populations were added to the reference in 2022. Pedigree imputation with findhap has been used to fill missing genotypes from the GGP-F250, as well as low probability calls from low-coverage WGS. Loss-of-function variants were identified using snpEff with the bovine assembly and Ensembl annotation that was current at the time. Allele frequencies across the SFA populations were determined, and the minor allele for each LOF variant was counted as the LOF allele. Genotypes were coded as 0, 1 or 2 copies of the LOF allele. Non-integer genotypes based on the imputed allele and allele frequency were assigned to partial genotypes imputed by findhap. The LOF count for each individual was the sum of their genotypes for each LOF variant. Within each composite, the difference between control and select mean LOF has tended to increase each year: 5.6'1.1 LOF per year for MARC I and IA, 6.4'1.1 for MARC II and 6.0'1.3 for MARC III. The difference between control and select LOF means for Angus, however, fluctuated around 18.6 without a clear trend for the difference to increase over time (0.3'1.3 LOF per year). Further examination of these populations is needed to better understand selection for LOF and correlated responses that may occur in production traits. The USDA is an equal opportunity provider and employer.