Consanguinity and the sib-pair method: An approach using identity by descent between and within individuals

Journal Article · Fri Nov 01 04:00:00 EST 1996 · American Journal of Human Genetics

OSTI ID:508234

Genin, E; Clerget-Darpoux, F ^[1]

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1. Institut National d`Etudes Demographiques, Paris (France)

To test for linkage between a trait and a marker, one can consider identical marker alleles in related individuals, for instance, sibs. For recessive diseases, it has been shown that some information may be gained from the identity by descent (IBD) of the two alleles of an affected inbred individual at the marker locus. The aim of this paper is to extend the sib-pair method of linkage analysis to the situation of sib pairs sampled from consanguineous populations. This extension takes maximum advantage of the information provided by both the IBD pattern between sibs and allelic identity within each sib of the pair. This is possible through the use of the condensed identity coefficients. Here, we propose a new test of linkage based on a {Chi}{sup 2}. We compare the performance of this test with that of the classical {Chi}{sup 2} test based on the distribution of sib pairs sharing 0, 1, or 2 alleles IBD. For sib pairs from first-cousin matings, the proposed test can better detect the role of a disease-susceptibility (DS) locus. Its power is shown to be greater than that of the classical test, especially for models where the DS allele may be common and incompletely penetrant; that is to say for situations that may be encountered in multifactorial diseases. A study of the impact of inbreeding on the expected proportions of sib pairs sharing 0, 1, or 2 alleles IBD is also performed here. Ignoring inbreeding, when in fact inbreeding exists, increases the rate of type I errors in tests of linkage. 21 refs., 8 figs., 9 tabs.

• OSTI ID: 508234
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 5 Vol. 59; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 GENERAL AND MISCELLANEOUS
BIOLOGICAL MARKERS
GENES
GENETIC MAPPING
GENETICS
HEREDITARY DISEASES
MATHEMATICAL MODELS
PATIENTS
PHENOTYPE
RECESSIVE MUTATIONS
RISK ASSESSMENT
STATISTICAL MODELS