Phylogenetics applied to genotype/phenotype association and selection analyses with sequence data from angptl4 in humans

Taylor J Maxwell; Matthew L Bendall; Jeffrey Staples; Todd Jarvis; Keith A Crandall

doi:10.3390/ijms11010370

Phylogenetics applied to genotype/phenotype association and selection analyses with sequence data from angptl4 in humans

Int J Mol Sci. 2010 Jan 25;11(1):370-85. doi: 10.3390/ijms11010370.

Authors

Taylor J Maxwell¹, Matthew L Bendall, Jeffrey Staples, Todd Jarvis, Keith A Crandall

Affiliation

¹ Human Genetics Center, University of Texas School of Public Health, Houston, 77030, USA. Taylor.J.Maxwell@uth.tmc.edu <Taylor.J.Maxwell@uth.tmc.edu>

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.

Keywords: ANGPTL4; TreeSAAP; association studies; phylogenetics; selection; treescan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiopoietin-Like Protein 4
Angiopoietins / genetics*
Angiopoietins / metabolism*
Computational Biology / methods
Genetic Association Studies
Genetic Variation
Genotype*
Haplotypes
Humans
Open Reading Frames
Phenotype*
Phylogeny*
Selection, Genetic*

Substances

ANGPTL4 protein, human
Angiopoietin-Like Protein 4
Angiopoietins