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Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection

Zavattari, Patrizia and Deidda, Elisabetta and Whalen, Michael B. and Lampis, Rosanna and Mulargia, Annapaola and Loddo, Miriam and Eaves, Iain A. and Mastio, Giuseppe and Todd, John A. and Cucca, Francesco (2000) Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection. Human Molecular Genetics, Vol. 9 (20), p. 2947-2958. eISSN 1460-2083. Article.

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Abstract

Linkage disequilibrium (LD) mapping of disease genes is complicated by population- and chromosome-region-specific factors. We have analysed demographic factors by contrasting intermarker LD results obtained in a large cosmopolitan population (UK), a large genetic isolate (Sardinia) and a subisolate (village of Gavoi) for two regions of the X chromosome. A dramatic increase of LD was found in the subisolate. Demographic history of populations therefore influences LD. Chromosome-region-specific effects, namely the pattern and frequency of homologous recombination, were next delineated by the analysis of chromosome 6p21, including the HLA region. Patterns of global LD in this region were very similar in the UK and Sardinian populations despite their entirely distinct demographies, and correlate well with the pattern of recombinations. Nevertheless, haplotypes extend across recombination hot spots indicative of selection of certain haplotypes. Subisolate aside, chromosome-region-specific differences in LD patterns appear to be more important than the differences in intermarker LD between distinct populations.

Item Type:Article
ID Code:4228
Status:Published
Refereed:Yes
Uncontrolled Keywords:Dependent diabetes-mellitus, gametic disequilibrium, disease genes, association, microsatellites, complex, mhc, map, resolution, family, Sardinia
Subjects:Area 06 - Scienze mediche > MED/03 Genetica medica
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
002 Altri enti e centri di ricerca del Nord Sardegna > Azienda ASL3, Nuoro
Publisher:Oxford University Press
eISSN:1460-2083
Deposited On:21 Jul 2010 10:55

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