Genetic linkage of mild malaria to the major histocompatibility complex in Gambian children: study of affected sibling pairs
BMJ 1997; 315 doi: https://doi.org/10.1136/bmj.315.7100.96 (Published 12 July 1997) Cite this as: BMJ 1997;315:96
- Annette Jepson, Wellcome Trust career development fellowa,
- Fatoumatta Sisay-Joof, higher scientific officerb,
- Winston Banya, statisticianb,
- Musa Hassan-King, scientistb,
- Angela Frodsham, research assistanta,
- Stephen Bennett, senior lecturerc,
- Adrian Hill, professor of human geneticsa,
- Hilton Whittle, deputy directorb
- a Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN
- b Medical Research Council Laboratories, Fajara, The Gambia
- c Tropical Health Epidemiology Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT
- Correspondence to: Dr Jepson
- Accepted 12 December 1996
Introduction
Case-control studies have shown that genes for the major histocompatibility complex influence the presentation and outcome of severe Plasmodium falciparum disease (cerebral malaria or severe anaemia).1 2 To assess the role of these genes in mild disease, we conducted a genetic analysis of sibling pairs concordant for this phenotype. The affected sib-pair method compares the observed and expected distribution of parental alleles at marker loci inherited identical by descent (ibd). At any locus, a pair of siblings may share 0, 1, or 2 alleles in the ratio 25%:50%:25%, by random segregation. If a locus is genetically linked to disease, affected siblings will share a higher number of alleles identical by descent at that locus than expected.
Subjects, methods, and results
We recruited 217 dizygous pairs of Gambian twins (mean age 5.3 …