4.8 Article

Natural selection on genes that underlie human disease susceptibility

Journal

CURRENT BIOLOGY
Volume 18, Issue 12, Pages 883-889

Publisher

CELL PRESS
DOI: 10.1016/j.cub.2008.04.074

Keywords

-

Funding

  1. NIGMS NIH HHS [GM077959, GM79558, R01 GM079558, R01 GM072861-05, R01 GM077959, R01 GM072861] Funding Source: Medline

Ask authors/readers for more resources

What evolutionary forces shape genes that contribute to the risk of human disease? Do similar selective pressures act on alleles that underlie simple versus complex disorders [1-3]? Answers to these questions will shed light onto the origin of human disorders (e.g., [4]) and help to predict the population frequencies of alleles that contribute to disoase risk, with important implications for the efficient design of mapping studies [5-7]. As a first step toward addressing these questions, we created a hand-curated version of the Mendelian Inheritance in Man database (OMIM). We then examined selective pressures on Mendelian-disease genes, genes that contribute to complex-disease risk, and genes known to be essential in mouse by analyzing patterns of human polymorphism and of divergence between human and rhesus macaque. We found that Mendel ian-disease genes appear to be under widespread purifying selection, especially when the disease mutations are dominant (rather than recessive). In contrast, the class of genes that influence complex-disease risk shows little signs of evolutionary, conservation, possibly because this category includes targets of both purifying and positive selection.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available