A survey of the population genetic variation in the human kinome

  • Zhang W
  • Catenacci D
  • Duan S
 et al. 
  • 1

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.

Abstract

Protein kinases are key regulators of various biological processes, such as control of cell growth, metabolism, differentiation and apoptosis. Therefore, protein kinases have been an important class of targets for anticancer drugs. Health-related disparities such as differential drug response have been observed between human populations. A survey of the human kinases and their ligand genes for those containing population-specific genetic variants could provide new insights into the mechanisms of these health disparities and suggest novel targets for ethnicity-specific personalized medicine. Using the International HapMap Project genotypic data on single-nucleotide polymorphisms (SNPs), the protein kinase complement of the human genome (kinome) and some experimentally verified ligand genes were scanned for the existence of population-specific SNPs (eSNPs). In general, protein kinases were found to contain a much higher proportion of eSNPs than the whole genome background, indicating a stronger pressure for adaptation in individual populations. In contrast, the proportion of ligand genes containing eSNPs was not different from that of the whole genome background. Although with some important limitations, our results suggest that human kinases are more likely to be under recent positive selection than ligands. Our findings suggest that the health-related disparities associated with kinase signaling pathways are more likely to be driven by the genetic variation in the kinase genes than their cognate ligands. Illustrating the role of molecular evolution in the genetic variation of the human kinome could provide a promising route to understand the ethnic differences in cancer and facilitate the realization of ethnicity-based individualized medicine. © 2009 The Japan Society of Human Genetics All rights reserved.

Author-supplied keywords

  • HapMap
  • Kinase
  • Kinome
  • Ligand
  • Single-nucleotide polymorphism

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • W. Zhang

  • D.V.T. Catenacci

  • S. Duan

  • M.J. Ratain

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free