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Larry A Kuehn

Publications and source records attributed to Larry A Kuehn.

2 recordsLinked to original sources

Genomic prediction and genome-wide association study for liver abscesses in crossbred beef cattle.

Liver abscesses are a concern in feedlot cattle, and little is known about the role of genetics in their development. This study aimed to estimate genetic parameters and to identify single-nucleotide polymorphisms (SNPs) associated with liver abscesses. Crossbred cattle representing 18 breeds in the U.S. Meat Animal Research Center Germplasm Evaluation Program were phenotyped for liver abscesses at slaughter (n&#x2005;=&#x2005;9,044). Seventeen percent of cattle had liver abscesses. These cattle had genotypes that were imputed to sequence variant genotypes. After filtering and quality control, 340,723 SNPs were used in the analysis. Liver abscess prevalence was modeled with a single-step genomic best linear unbiased prediction (ssGBLUP) threshold model using a Bayesian framework. The model included contemporary group (sex, treatment group, and slaughter date), additive genomic, and residual effects. Genomic heritability was 0.039 (95% highest posterior density&#x2005;=&#x2005;0.005, 0.081), which was very small. To assess prediction quality, a 5-fold random cross-validation structure was used. Method Linear Regression was used to assess accuracy, bias, and dispersion by comparing estimated breeding values (EBV) from full and reduced analyses. Cross-validation metrics showed EBV based on genotypes had 0.05 reliability (SD&#x2005;<&#x2005;0.01) with no bias relative to EBV based on genotypes and phenotypes. For the genome-wide association study, SNP effects were back calculated from the EBV solutions from ssGBLUP. No SNPs were associated with liver abscesses at a Benjamini-Hochberg adjusted 0.05 significance level. Although a large dataset was used, this result was because of the low genomic heritability and imprecise EBV used to calculate SNP effects. Based on these results, environmental factors contribute to most of the variation in liver abscesses. Genetic selection to reduce liver abscesses would be slow because of the low genomic heritability, measurement late in life, and inability to measure breeding animals. A faster approach would be finding additional environmental interventions that maintain animal performance.

Animals

A vision of how low-coverage sequence data should contribute to genetic evaluation in the future.

Low-coverage sequencing refers to sequencing DNA of individuals to a low depth of coverage (e.g., 0.5X) and imputing that sequence to a genomic sequence based on reference haplotypes from individuals sequenced to a high depth of coverage (e.g., &#x2265;10X). It has been proposed as an alternative to genotyping by Single-nucleotide polymorphisms (SNP) arrays. At least one commercial product based on it is available for agricultural species. Concerns limiting adoption in its current form are: 1) the cost of storing the huge volume of data it generates and 2) whether that additional data will result in improved accuracy of genetic evaluation. This work envisions future implementation of low-coverage sequencing to reduce storage costs and enhance genetic evaluations by leveraging the additional information in the full sequence of the pangenome to account for more genetic variation. We propose addressing the storage issue by representing genomic sequence of an individual in a pair of haplotype arrays with each element pointing to an enumerated haplotype of the sequence within one of approximately 50,000 defined genome segments. Assuming 60 million genomic variants, the infrastructure required to translate the identifier of any enumerated haplotype into its genomic sequence would require less than 10 gigabytes of binary storage. Each haplotype array element would require 2 bytes, so the marginal binary storage required to represent the genomic sequence of an individual would be about 200 kilobytes (KB), similar to the genotypes from a SNP array with 200,000 markers. This assumes no pedigree and no ambiguity of the imputation, though the latter is unrealistic. Strategies to minimize, and when necessary, to manage and efficiently represent ambiguity are proposed. The genomic sequence of an individual could be stored in about 1 KB (binary) if both parents have unambiguous sequences stored as described above. The proposed system for representing the pangenome includes algorithms for read mapping and imputation intended to leverage all known genetic variation in the target population. It is also designed to use sequencing reads generated for imputing the genomic sequence of new individuals to identify unrecognized mutations, crossovers, and structural variants, thus continuously improving the genome representation, especially if widespread use of low-coverage sequencing in livestock industries is realized. This could make improved genetic merit and management of livestock feasible without computational burden.

Animals