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Chapter 062. Principles of
Human Genetics
(Part 28)
Allelic Association, Linkage Disequilibrium, and Haplotypes
Allelic association refers to a situation in which the frequency of an allele is
significantly increased or decreased in individuals affected by a particular disease
in comparison to controls.
Linkage and association differ in several aspects. Genetic linkage is
demonstrable in families or sibships. Association studies, on the other hand,
compare a population of affected individuals with a control population.
Association studies can be performed as case-control studies that include
unrelated affected individuals and matched controls, or as family-based studies
that compare the frequencies of alleles transmitted or not transmitted to affected
children.
Allelic association studies are particularly useful for identifying
susceptibility genes in complex diseases. When alleles at two loci occur more
frequently in combination than would be predicted (based on known allele
frequencies and recombination fractions), they are said to be in linkage
disequilibrium . In Fig. 62-13, a mutation, Z, has occurred at a susceptibility locus
where the normal allele is Y.
The mutation is in close proximity to a genetic polymorphism with allele A
or B. With time, the chromosomes carrying the A and Z alleles accumulate and
represent 10% of the chromosomes in the population.
The fact that the disease susceptibility gene, Z, is found preferentially, or
exclusively, in association with the A allele illustrates linkage disequilibrium.
Though not all chromosomes carrying the A allele carry the disease gene,
the A allele is associated with an increased risk because of its possible association
with the Z allele.
This model implies that it may be possible in the future to identify Z