? The European colonial period beginning in the late 1400s brought previously isolated populations together in the New World; thus, many US residents can trace their ancestry to more than one continent. Studying the impact of genetic admixture is important because variation in individual admixture proportions can be a confounding factor in ordinary genetic association studies, and because the genetic structure of admixed populations can facilitate the detection and localization of genes underlying ethnic variation in disease risk. We have demonstrated the usefulness of study designs that exploit the ability to model admixture for: (1) Distinguishing genetic and environmental explanations for ethnic differences in disease risk (and investigating the mode of inheritance), by studying the relationship of disease risk to individual admixture; (2) Controlling for confounding of genetic associations in stratified populations by modeling individual and population admixture; and (3) Admixture mapping: localizing genes that underlie ethnic differences in disease risk. Indeed, one of the greatest areas of promise in admixture studies is gene mapping, which can be accomplished by testing for association between the disease and locus ancestry after conditioning on parental admixture. The advantage of admixture mapping is it has higher statistical power compared to family linkage studies. Application of these approaches to admixed populations such as African Americans, Mexican Americans and Puerto Ricans, not only requires further development of the statistical methods, but also additional markers informative for ancestry. A genome spanning panel of Ancestry Informative Markers (AIMs) is needed for distinguishing European, West African and Native American ancestry.
AIMs have the primary feature of large differences in allele frequency between the parental populations. Of the three study designs listed above, typically 100 AIMs from across the genome are needed to estimate individual admixture proportions for (1) and (2). However, design (3) necessitates markers at much higher density because it depends upon inferring ancestry at each locus. From simulation studies, we estimate that about 1000 AIMs will be required for genome-wide mapping with two-way admixture, and about 1500 for admixture between three populations. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
2R01HG002154-04A2
Application #
6777197
Study Section
Genome Study Section (GNM)
Program Officer
Brooks, Lisa
Project Start
1999-09-24
Project End
2007-06-30
Budget Start
2004-09-30
Budget End
2005-06-30
Support Year
4
Fiscal Year
2004
Total Cost
$300,000
Indirect Cost
Name
Pennsylvania State University
Department
Social Sciences
Type
Schools of Arts and Sciences
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
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