A class of tests for linkage using affected pedigree members
A.S. Whittemore,J. Halpern
Biometrics, 50(1),118-127
(Mar 1994)
Abstract
We describe a class of nonparametric tests for linkage between a
marker and a gene assumed to exist and to govern susceptibility to a
disease. The tests are formed by assigning a score to each possible
pattern of marker allele sharing (identity-by-descent) among
affected pedigree members, and then averaging the scores over all
patterns compatible with the observed marker genotype and
genealogical relationship of the affected members. Different score
functions give different tests. One function, which examines marker
allele similarity across pairs of affected pedigree members, gives a
test similar to that of Fimmers et al. (1989, in Multipoint Mapping
and Linkage Based on Affected Pedigree Members: Genetic Analysis
Workshop, R. C. Elston, M. A. Spence, S. E. Hodge, and J. W.
MacCluer (eds), 123-128; City: Alan R. Liss). A second function
examines allele similarity across arbitrary subsets, not just pairs,
of affected members. The resulting test can be more powerful than
the one based solely on pairs of affected members. The approach has
several advantages: it does not require knowledge of the mode of
disease inheritance; it does not require unambiguous determination
of identity-by-descent at the marker; it does not suffer from
variability due to chance allele similarity among affected members
who are unrelated, such as spouses; it allows marker genotypes of
unaffected members to contribute information on allele sharing among
the affected; it permits calculation of exact P-values.
Computational requirements limit the tests to many pedigrees with
few (< 16) affected members.
Allele-sharing linkage analysis