Abstract
Genotype/phenotype association analyses (Treescan) with plasma lipid levels and functional site prediction methods (TreeSAAP and PolyPhen) were performed using sequence data for ANGPTL4 from 3,551 patients in the Dallas Heart Study. Biological assays of rare variants in phenotypic tails and results from a Treescan analysis were used as “known” variants to assess the site prediction abilities of PolyPhen and TreeSAAP. The E40K variant in European Americans and the R278Q variant in African Americans were significantly associated with multiple lipid phenotypes. Combining TreeSAAP and PolyPhen performed well to predict “known” functional variants while reducing noise from false positives.
Highlights
No single method of analysis is sufficient to uncover all the information that can come from sequence data
This suggests that LDL probably contributes most to the association in the presence of the other variables followed by triglycerides while the univariate association of VLDL is probably accounted for correlations between the phenotypes
Using ω = 1 as the threshold between positive and negative selection, these results indicate that the coiled-coil domain is under nearly neutral selection, while the fibrinogen-like domain is under strong purifying selection
Summary
No single method of analysis is sufficient to uncover all the information that can come from sequence data. What we can strive for is a set of methods that complement each other. The fields of molecular evolution, phylogenetics, and population genetics have a long history of. 2010, 11 sequence analysis [1,2]; these methods do not typically use phenotype information. Sci. 2010, 11 sequence analysis [1,2]; these methods do not typically use phenotype information Many of these methods use knowledge about gene structure, amino acids, protein structure, and phylogenetics
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