MAPPING BY ADMIXTURE LINKAGE
DISEQUILIBRIUM: ADVANCES, LIMITATIONS AND
GUIDELINES
The main principles in this paper that have also been addressed in lectures are linkage
disequilibrium and admixture. Firstly, linkage disequilibrium is the non-random
association of alleles on different loci, which have ancestral origins on the same
chromosome. As a result, these alleles are not independent of each other. Secondly,
admixture is the process of interbreeding between two previously genetically
divergent populations, which gives rise to a new population. The offspring can then
interbreed with the parental populations to provide more genetic variation. These two
processes can be viewed together as admixture linkage disequilibrium. The new
genetic variants that result from admixture have massive gene flow that can be studied
closely. There is linkage disequilibrium between all loci with high allele-frequency
differences between the parental populations. In this paper, mapping by admixture
linkage disequilibrium (MALD) is being tried as a new approach for studying and
mapping genetic variants associated with human disease. In particular, it studies the
long-range haplotypes that are formed as a result of recent admixture in AfricanAmerican and Latino populations.
This paper does not address a hypothesis/alternative hypothesis explicitly, however,
alternative methods to MALD are addressed, including linkage mapping and genetic
association mapping. Linkage mapping can only be used for rare, monogenic,
Mendelian family-studies and although genetic association mapping can be used for
complex diseases, the process requires many more markers and can often be
expensive. This paper explains that MALD would be less expensive as it includes
only around 2000 markers, but will also have greater accuracy when studying the
effects of multiple genes on a complex disease.
What makes MALD different to other genetic associations studies is that only the
genomes of individuals who have mixed ancestry and who suffer from diseases of
interest are eligible to take part. The people who fit these inclusion criteria are then
progressed further in the study. The sample sizes required to make a statistically
sound estimate of disease-associated alleles varies depending on the initial parental
ancestries and the disease in question. As MALD is a new approach, there are no
definitive results, only estimates at the sample sizes. Instead this paper addresses the
theory behind it and the possible future implications.
Genotype data were collected from human individuals who were of mixed ancestry,
and were also affected by a disease of interest. These, and control cases, were then
screened against a set of polymorphic markers. These markers allow you to determine
the ancestry of individual genes in the whole genome. Additionally, chromosomal
regions that have higher than average disease-gene incidences are identified. From all
of this, the disease-causing alleles can be determined by studying the high incidence
of nearby SNPs.