Title

Mapping by Admixture Linkage Disequilibrium in Human Populations: Limits and Guidelines

Authors

J. Claiborne Stephens, National Cancer Institute at Frederick
D. Briscoe, National Cancer Institute at Frederick
Stephen J. O'Brien, National Cancer Institute at FrederickFollow

Document Type

Article

Publication Date

10-1994

Publication Title

American Journal of Human Genetics

ISSN

0002-9297

Volume

55

Issue/No.

4

First Page

809

Last Page

824

Abstract

Certain human hereditary conditions, notably those with low penetrance and those which require an environmental event such as infectious disease exposure, are difficult to localize in pedigree analysis, because of uncertainty in the phenotype of an affected patient's relatives. An approach to locating these genes in human cohort studies would be to use association analysis, which depends on linkage disequilibrium of flanking polymorphic DNA markers. In theory, a high degree of linkage disequilibrium between genes separated by 10-20 cM will be generated and persist in populations that have a history of recent (3-20 generations ago) admixture between genetically differentiated racial groups, such as has occurred in African Americans and Hispanic populations. We have conducted analytic and computer simulations to quantify the effect of genetic, genomic, and population parameters that affect the amount and ascertainment of linkage disequilibrium in populations with a history of genetic admixture. Our goal is to thoroughly explore the ranges of all relevant parameters or factors (e.g., sample size and degree of genetic differentiation between populations) that may be involved in gene localization studies, in hopes of prescribing guidelines for an efficient mapping strategy. The results provide reasonable limits on sample size (200-300 patients), marker number (200-300 in 20-cM intervals), and allele differentiation (loci with allele frequency difference of > or = .3 between admixed parent populations) to produce an efficient approach (> 95% ascertainment) for locating genes not easily tracked in human pedigrees.

Comments

© 1994 by The American Society of Human Genetics

Additional Comments

PMC1918304

NSUWorks Citation

Stephens, J. Claiborne; D. Briscoe; and Stephen J. O'Brien. 1994. "Mapping by Admixture Linkage Disequilibrium in Human Populations: Limits and Guidelines." American Journal of Human Genetics 55, (4): 809-824. https://nsuworks.nova.edu/cnso_bio_facarticles/264

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015