Comparative Genomics Approaches Accurately Predict Deleterious Variants in Plants

G3: Genes, Genomes, Genetics

article

Thomas J.Y. Kono¹  Li Lei¹  Ching-Hua Shih²  Paul J. Hoffman¹  Peter L. Morrell¹  Justin C. Fay² 

[1] Department of Agronomy & Plant Genetics, University of Minnesota, St. Paul, MN 551085;Department of Genetics, Washington University, St. Louis, MO 63110

关键词: deleterious mutations;    phenotypes;    genome;    training set;   

DOI  :  10.1534/g3.118.200563

学科分类：社会科学、人文和艺术（综合）

来源: Genetics Society of America

【 摘 要 】

Recent advances in genome resequencing have led to increased interest in prediction of the functional consequences of genetic variants. Variants at phylogenetically conserved sites are of particular interest, because they are more likely than variants at phylogenetically variable sites to have deleterious effects on fitness and contribute to phenotypic variation. Numerous comparative genomic approaches have been developed to predict deleterious variants, but the approaches are nearly always assessed based on their ability to identify known disease-causing mutations in humans. Determining the accuracy of deleterious variant predictions in nonhuman species is important to understanding evolution, domestication, and potentially to improving crop quality and yield. To examine our ability to predict deleterious variants in plants we generated a curated database of 2,910 Arabidopsis thaliana mutants with known phenotypes. We evaluated seven approaches and found that while all performed well, their relative ranking differed from prior benchmarks in humans. We conclude that deleterious mutations can be reliably predicted in A. thaliana and likely other plant species, but that the relative performance of various approaches does not necessarily translate from one species to another.

【 授权许可】

CC BY|CC BY-NC