Trait Association and Prediction Through Integrative K-mer Analysis
2021
Genome-wide association study (GWAS) with single nucleotide polymorphisms (SNPs) has been widely used to explore genetic controls of phenotypic traits. Here we employed an GWAS approach using k-mers, short substrings from sequencing reads. Using maize cob and kernel color traits, we demonstrated that k-mer GWAS can effectively identify associated k-mers. Co-expression analysis of kernel color k-mers and pathway genes directly found k-mers from causal genes. Analyzing complex traits of kernel oil and leaf angle resulted in k-mers from both known and candidate genes. Evolution analysis revealed most k-mers positively correlated with kernel oil were strongly selected against in maize populations, while most k-mers for upright leaf angle were positively selected. In addition, phenotypic prediction of kernel oil, leaf angle, and flowering time using k-mer data showed at least a similarly high prediction accuracy to the standard SNP-based method. Collectively, our results demonstrated the bridging role of k-mers for data integration and functional gene discovery.
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