Nonparametric methods of linkage analysis (2)
Affected sib pair analysis
By chance, a pair of siblings will inherit the same two alleles of a
marker with probability 0.25, one allele with probability 0.5 and two
different alleles with probability 0.25. However if the siblings are both
affected and the marker is linked to a susceptibility locus then marker
alleles will be shared more frequently. This will be so whatever is the
mode of transmission of the disease locus.
If the data available make it clear that two siblings have inherited the
same parental allele they are said to be identical-by-descent (IBD) for this
allele.
The siblings are identical-by-descent for allele C from the mother
and allele B from the father.
If the two alleles appear the same but one cannot be sure that they
originate from the same parental allele then they are described as
identical-by-state (IBS).
Although the siblings are identical-by-state for both alleles,
there is a variety of possible parental genotypes (e.g. CC-BB, BC-BC,
CC-Bx, Cx-BB, Cx-Bx). Only the Cx-Bx combination would imply that the
alleles were also identical-by-descent.
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