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Titolo:
The extent of linkage disequilibrium in four populations with distinct demographic histories
Autore:
Dunning, AM; Durocher, F; Healey, CS; Teare, MD; McBride, SE; Carlomagno, F; Xu, CF; Dawson, E; Rhodes, S; Ueda, S; Lai, E; Luben, RN; Van Rensburg, EJ; Mannermaa, A; Kataja, V; Rennart, G; Dunham, I; Purvis, I; Easton, D; Ponder, BAJ;
Indirizzi:
Univ Cambridge, CRC, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England Univ Cambridge Cambridge England CB1 8RN Lab, Cambridge CB1 8RN, England Univ Cambridge, CRC, Genet Epidemiol Grp, Cambridge CB1 8RN, England Univ Cambridge Cambridge England CB1 8RN Grp, Cambridge CB1 8RN, England Univ Cambridge, EPIC, Cambridge CB1 8RN, England Univ Cambridge Cambridge England CB1 8RN PIC, Cambridge CB1 8RN, England GlaxoWellcome Med Res Ctr, UK Mol Genet, Cambridge, England GlaxoWellcome Med Res Ctr Cambridge England l Genet, Cambridge, England Sanger Ctr, Cambridge, England Sanger Ctr Cambridge EnglandSanger Ctr, Cambridge, England Glaxo Wellcome Inc, US Discovery Genet, Res Triangle Pk, NC 27709 USA Glaxo Wellcome Inc Res Triangle Pk NC USA 27709 Triangle Pk, NC 27709 USA Univ Pretoria, Dept Human Genet, ZA-0002 Pretoria, South Africa Univ Pretoria Pretoria South Africa ZA-0002 -0002 Pretoria, South Africa Kuopio Univ Hosp, Dept Clin Genet, SF-70210 Kuopio, Finland Kuopio Univ Hosp Kuopio Finland SF-70210 Genet, SF-70210 Kuopio, Finland Kuopio Univ Hosp, Dept Radiotherapy & Oncol, SF-70210 Kuopio, Finland Kuopio Univ Hosp Kuopio Finland SF-70210 Oncol, SF-70210 Kuopio, Finland Carmel Med Ctr, Dept Community Med & Epidemiol, Haifa, Israel Carmel Med Ctr Haifa Israel pt Community Med & Epidemiol, Haifa, Israel Technion Israel Inst Technol, Fac Med, Dept Community Med & Epidemiol, Haifa, Israel Technion Israel Inst Technol Haifa Israel ed & Epidemiol, Haifa, Israel
Titolo Testata:
AMERICAN JOURNAL OF HUMAN GENETICS
fascicolo: 6, volume: 67, anno: 2000,
pagine: 1544 - 1554
SICI:
0002-9297(200012)67:6<1544:TEOLDI>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
OVARIAN-CANCER; MAPPING GENES; GENOME; SEQUENCE; SUSCEPTIBILITY; MUTATIONS; VARIANTS; BREAST; LOCUS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Dunning, AM Univ Cambridge, CRC, Dept Oncol, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England Univ Cambridge Worts Causeway CambridgeEngland CB1 8RN gland
Citazione:
A.M. Dunning et al., "The extent of linkage disequilibrium in four populations with distinct demographic histories", AM J HU GEN, 67(6), 2000, pp. 1544-1554

Abstract

The design and feasibility of whole-genome-association studies are critically dependent on the extent of linkage disequilibrium (LD) between markers. Although there has been extensive theoretical discussion of this, few empirical data exist. The authors have determined the extent of LD among 38 biallelic markers with minor allele frequencies >.1, since these are most comparable to the common disease-susceptibility polymorphisms that association studies aim to detect. The markers come from three chromosomal regions-1,335 kb on chromosome 13q12-13, 380 kb on chromosome 19q13.2, and 120 kb on chromosome 22q13.3-which have been extensively mapped. These markers were examined in similar to1,600 individuals from four populations, all of Europeanorigin but with different demographic histories; Afrikaners, Ashkenazim, Finns, and East Anglian British. There are few differences, either in allelefrequencies or in LD, among the populations studied. A similar inverse relationship was found between LD and distance in each genomic region and in each population. Mean D' is .68 for marker pairs <5 kb apart and is .24 for pairs separated by 10-20 kb, and the level of LD is not different from thatseen in unlinked marker pairs separated by >500 kb. However, only 50% of marker pairs at distances <5 kb display sufficient LD (<Delta> > .3) to be useful in association studies. Results of the present study, if representative of the whole genome, suggest that a whole-genome scan searching for common disease-susceptibility alleles would require markers spaced less than orequal to5 kb apart.

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Documento generato il 03/07/20 alle ore 16:51:24