heterozygote advantage

heterozygote advantage - Human Molecular Genetics 2004 Vol...

Info iconThis preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon
Patterns of ethnic diversity among the genes that influence AIDS Cheryl Winkler 1 , Ping An 1 and Stephen J. O’Brien 2, * 1 Basic Research Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD 21702, USA and 2 Laboratory of Genomic Diversity, NCI-Frederick, Frederick, MD 21702, USA Received January 20, 2004; Revised and Accepted January 27, 2004 Although HIV-1/AIDS emerged late in the last century, more than 42 million individuals have been infected and 25 million have died worldwide, making AIDS, like malaria, a strong selective force for disease- associated genetic factors. Many of the genes that mediate immune response or that are co-opted by HIV-1 for completion of its lifecycle show differences in allele frequencies, as a result of drift, migration or selection. Here we show that the majority of AIDS candidate genes and AIDS restriction genes show signiFcant differences in allele frequencies, possibly the result of historic selective pressures. These genes are undergoing present day natural selection in populations with high AIDS prevalence. INTRODUCTION Since the geographic dispersal of modern humans 100 000– 150 000 years ago, the human genome has been shaped by evolutionary and historical forces (1–4). The migration out of Africa to Asia and Europe, estimated to have involved an effective population size of 10 000 (5,6), was followed by rapid expansion of human populations, tending to limit both allele and haplotype diversity in non-African populations relative to African populations (7). Recent migratory events, such as the forced removal of people from western Africa to colonies in the Americas and diaspora of many ethnic groups have also shaped human populations by genetic admixture (8–11). In addition, periodic outbreaks of deadly infectious agents and regional environmental pressures have modiFed the genetic architecture of disease gene allelic variation in local human populations (12,13). The best evidence for the in±uence of human pathogens on natural selection comes from studies of host genetic resistance to malaria and AIDS. Malaria became endemic 6000–10 000 years ago, coincident with the rise of agriculture, while AIDS emerged within the last 30 years (14–18). Malaria causes signiFcant mortality, particularly among children and pregnant women, and this selective pressure over 300–500 generations has resulted in adaptive shifts in the allele frequency of several genes with a role in malaria resistance (12,18–21). Among these are: the X-linked glucose-6-phosphate dehydrogenase ( G6pd ), the Duffy antigen receptor for chemokines ( DARC ), and the a - and b -globin genes, each of which show geographical differences in allele frequencies correlated with the occurrence of malaria (12,18,21–23). Association studies have also implicated HLA -B and HLA -DR, ICAM -1, TNF , NOS type 2 and CD 36 as having a modifying role in malaria susceptibility and resistance (reviewed in 12). Recent studies have shown that the strong selective pressure of malaria in sub- Saharan Africa has left its signature in the form of extended
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 2
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 06/18/2008 for the course BIO intro taught by Professor Titus during the Spring '08 term at SUNY Fredonia.

Page1 / 11

heterozygote advantage - Human Molecular Genetics 2004 Vol...

This preview shows document pages 1 - 2. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online