Efficient strategies for genomic searching using the affected-pedigree-member method of linkage analysis
- Univ. of Pittsburgh, PA (United States)
The affected-pedigree-member (APM) method of linkage analysis is a nonparametric statistic that tests for nonrandom cosegregation of a disease and marker loci. The APM statistic is based on the observation that if a marker locus is near a disease-susceptibility locus, then affected individuals within a family should be more similar at the marker locus than is expected by chance. The APM statistic measures marker similarity in terms of identity by state (IBS) of marker alleles; that is, two alleles are IBS if they are the same, regardless of their ancestral origin. Since the APM statistic measures increased marker similarity, it makes no assumptions concerning how the disease is inherited; this can be an advantage when dealing with complex diseases for which the mode of inheritance is difficult to determine. The authors investigate here the power of the APM statistic to detect linkage in the context of a genomewide search. In such a search, the APM statistic is evaluated at a grid of markers. Then regions with high APM statistics are investigated more thoroughly by typing more markers in the region. Using simulated data, they investigate various search strategies and recommended an optimal search strategy that maximizes the power to detect linkage while minimizing the false-positive rate and number of markers. They determine an optimal series of three increasing cut-points and an independent criterion for significance. 14 refs., 7 figs., 4 tabs.
- OSTI ID:
- 7285326
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 54:3; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
Similar Records
Some developments on the affected-pedigree-member method of linkage analysis
Genetic linkage of familial granulomatous inflammatory arthritis, skin rash, and uveitis to chromosome 16