GENEALOGY-DNA-L Archives

From: "Steven C. Perkins" <>
Subject: MAPPING BY ADMIXTURE LINKAGE DISEQUILIBRIUM: ADVANCES,LIMITATIONS AND GUIDELINES (abstract)
Date: Mon, 01 Aug 2005 15:29:51 -0500

Nature Reviews Genetics 6, 623-632 (2005); doi:10.1038/nrg1657


MAPPING BY ADMIXTURE LINKAGE DISEQUILIBRIUM: ADVANCES, LIMITATIONS AND
GUIDELINES

Michael W. Smith & Stephen J. O'Brien about the authors

Abstract

Mapping by admixture linkage disequilibrium (MALD) is a theoretically
powerful, although unproven, approach to mapping genetic variants that are
involved in human disease. MALD takes advantage of long-range haplotypes
that are generated by gene flow among recently admixed ethnic groups, such
as African-Americans and Latinos. Under ideal circumstances, MALD will have
more power to detect some genetic variants than other types of genome-wide
association study that are carried out among more ethnically homogeneous
populations. It will also require 200–500 times fewer markers, providing a
significant economic advantage. The MALD approach is now being applied,
with results expected in the near future.


Summary

* Mapping by admixture linkage disequilibrium (MALD) is a genetic
strategy for discovering genes that underlie complex diseases. The method
is based on differences in disease-gene frequency between the parental
racial groups of admixed populations.
* A MALD-based full-genome scan can be carried out using a few thousand
markers that are able to differentiate, to a high degree, between
chromosomal ancestries in relation to the parental popultions. This enables
the discovery of regions that harbour genes associated with complex diseases.
* Differences in the proportion of admixture for a particular
chromosomal segment between cases and controls can implicate a region that
is several centimorgans in size as being involved in a disease. This can
also be done using cases only, by looking for differences in admixture
proportions between specific locations and the rest of the genome in the
same individual.
* MALD-based genome scans are already possible in African-Americans,
and are now underway. These studies are using a published set of MALD
markers that are highly enriched for the ability to differentiate between
chromosomal segments derived from African and European ancestors. The
marker set will improve as frequency data accumulate from the HapMap project.
* MALD scans in other groups (Latinos, Pacific Islanders and other
admixed populations) will become possible in the near future as appropriate
markers are mined from HapMap allele frequencies.
* Proof of the efficacy of MALD awaits its successful application among
African-Americans for potentially amenable diseases, such as prostate
cancer, multiple sclerosis and end-stage renal disease. If these studies
are successful, MALD could then be applied to other groups over the next
few years.

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