Home LiteratureArticle Details
PMID: 10712211 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Significant admixture linkage disequilibrium across 30 cM around the FY locus in African Americans.

American journal of human genetics ·Vol. 66 ·No. 3 ·2000-03-00 ·Pages 969-78

Lautenberger JA, Stephens JC, O'Brien SJ, Smith MW

Abstract

Scientists, to understand the importance of allelic polymorphisms on phenotypes that are quantitative and environmentally interacting, are now turning to population-association screens, especially in instances in which pedigree analysis is difficult. Because association screens require linkage disequilibrium between markers and disease loci, maximizing the degree of linkage disequilibrium increases the chances of discovering functional gene-marker associations. One theoretically valid approach-mapping by admixture linkage disequilibrium (MALD), using recently admixed African Americans-is empirically evaluated here by measurement of marker associations with 15 short tandem repeats (STRs) and an insertion/deletion polymorphism of the AT3 locus in a 70-cM segment at 1q22-23, around the FY (Duffy) locus. The FY polymorphism (-46T-->C) disrupts the GATA promoter motif, specifically blocking FY erythroid expression and has a nearly fixed allele-frequency difference between European Americans and native Africans that is likely a consequence of a selective advantage of FY-/- in malaria infections. Analysis of linkage disequilibrium around the FY gene has indicated that there is strong and consistent linkage disequilibrium between FY and three flanking loci (D1S303, SPTA1, and D1S484) spanning 8 cM. We observed significant linkage-disequilibrium signals over a 30-cM region from -4.4 to 16.3 cM (from D1S2777 to D1S196) for STRs and at 26.4 cM (AT3), which provided quantitative estimates of centimorgan limits, by MALD assessment in African American population-association analyses, of 5-10 cM.

MeSH Terms
Africa/ethnology African Americans Alleles Blacks/genetics Chromosome Mapping/methods Chromosomes, Human, Pair 1/genetics DNA-Binding Proteins/physiology Duffy Blood-Group System/genetics Erythroid-Specific DNA-Binding Factors Europe/ethnology Gene Frequency/genetics Genetic Markers/genetics Haplotypes/genetics Humans Linkage Disequilibrium/genetics Models, Genetic Polymorphism, Genetic/genetics Promoter Regions, Genetic/genetics Tandem Repeat Sequences/genetics Transcription Factors/physiology United States
Chemicals
DNA-Binding Proteins Duffy Blood-Group System Erythroid-Specific DNA-Binding Factors Genetic Markers Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lautenberger J A
Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD, USA.
Stephens J C
O'Brien S J
Smith M W
References (43)
43 references, click to expand
  1. The genetic structure of admixed populations.
    Genetics. 1991 Feb;127(2):417-28 PMID: 2004712
  2. An STS-based map of the human genome.
    Science. 1995 Dec 22;270(5244):1945-54 PMID: 8533086
  3. Multipoint linkage disequilibrium mapping with particular reference to the African-American population.
    Genet Epidemiol. 1999;17(2):79-101 PMID: 10414554
  4. A comprehensive genetic map of the human genome based on 5,264 microsatellites.
    Nature. 1996 Mar 14;380(6570):152-4 PMID: 8600387
  5. The coding sequence of Duffy blood group gene in humans and simians: restriction fragment length polymorphism, antibody and malarial parasite specificities, and expression in nonerythroid tissues in Duffy-negative individuals.
    Blood. 1995 Feb 1;85(3):615-21 PMID: 7833466
  6. The acquired immunodeficiency syndrome in a cohort of homosexual men. A six-year follow-up study.
    Ann Intern Med. 1985 Aug;103(2):210-4 PMID: 2990275
  7. 'Unique' alleles in admixed populations: a strategy for determining 'hereditary' population differences of disease frequencies.
    Ethn Dis. 1991 Summer;1(3):245-56 PMID: 1842537
  8. Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency virus.
    JAMA. 1987 Jan 16;257(3):331-4 PMID: 3491911
  9. Estimating European admixture in African Americans by using microsatellites and a microsatellite haplotype (CD4/Alu).
    Hum Genet. 1999 Feb;104(2):149-57 PMID: 10190326
  10. A physical map of 30,000 human genes.
    Science. 1998 Oct 23;282(5389):744-6 PMID: 9784132
  11. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy.
    N Engl J Med. 1976 Aug 5;295(6):302-4 PMID: 778616
  12. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor.
    Science. 1993 Aug 27;261(5125):1182-4 PMID: 7689250
  13. Genetic dissection of complex traits.
    Science. 1994 Sep 30;265(5181):2037-48 PMID: 8091226
  14. Mapping genes underlying ethnic differences in disease risk by linkage disequilibrium in recently admixed populations.
    Am J Hum Genet. 1997 Jan;60(1):188-96 PMID: 8981962
  15. Ethnic-affiliation estimation by use of population-specific DNA markers.
    Am J Hum Genet. 1997 Apr;60(4):957-64 PMID: 9106543
  16. Marker selection for the transmission/disequilibrium test, in recently admixed populations.
    Am J Hum Genet. 1998 Mar;62(3):703-12 PMID: 9497257
  17. Human genetics: the molecular challenge.
    Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:1-13 PMID: 3472706
  18. Demographic history and linkage disequilibrium in human populations.
    Nat Genet. 1997 Dec;17(4):435-8 PMID: 9398845
  19. From malaria to chemokine receptor: the emerging physiologic role of the Duffy blood group antigen.
    Blood. 1997 May 1;89(9):3077-91 PMID: 9129009
  20. Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals.
    Nat Genet. 1995 Jun;10(2):224-8 PMID: 7663520
  21. Hemophilia growth and development study: baseline neurodevelopmental findings.
    J Pediatr Psychol. 1994 Apr;19(2):223-39 PMID: 8051604
  22. Characterization of the Duffy gene promoter: evidence for tissue-specific abolishment of expression in Fy(a-b-) of black individuals.
    Biochem Biophys Res Commun. 1996 May 24;222(3):852-9 PMID: 8651934
  23. Linkage disequilibrium in admixed populations: applications in gene mapping.
    J Hered. 1994 Jan-Feb;85(1):59-63 PMID: 8120361
  24. A transmission disequilibrium test for quantitative trait loci.
    Hum Hered. 1997 Nov-Dec;47(6):342-50 PMID: 9391826
  25. Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.
    Science. 1997 Aug 15;277(5328):959-65 PMID: 9252328
  26. Mapping genes that underlie ethnic differences in disease risk: methods for detecting linkage in admixed populations, by conditioning on parental admixture.
    Am J Hum Genet. 1998 Jul;63(1):241-51 PMID: 9634509
  27. The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models.
    Genetics. 1964 Jan;49(1):49-67 PMID: 17248194
  28. An E-M algorithm and testing strategy for multiple-locus haplotypes.
    Am J Hum Genet. 1995 Mar;56(3):799-810 PMID: 7887436
  29. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM).
    Am J Hum Genet. 1993 Mar;52(3):506-16 PMID: 8447318
  30. A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia.
    N Engl J Med. 1989 Oct 26;321(17):1141-8 PMID: 2477702
  31. The ALIVE study, a longitudinal study of HIV-1 infection in intravenous drug users: description of methods and characteristics of participants.
    NIDA Res Monogr. 1991;109:75-100 PMID: 1661376
  32. Admixture as a tool for finding linked genes and detecting that difference from allelic association between loci.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):9119-23 PMID: 3194414
  33. Multiple comparison procedures updated.
    Clin Exp Pharmacol Physiol. 1998 Dec;25(12):1032-7 PMID: 9888002
  34. Estimating African American admixture proportions by use of population-specific alleles.
    Am J Hum Genet. 1998 Dec;63(6):1839-51 PMID: 9837836
  35. Dinucleotide repeat polymorphism at the human erythroid alpha spectrin (SPTA1) locus.
    Hum Mol Genet. 1992 Jun;1(3):218 PMID: 1339473
  36. Mapping by admixture linkage disequilibrium in human populations: limits and guidelines.
    Am J Hum Genet. 1994 Oct;55(4):809-24 PMID: 7942858
  37. The distribution of linkage disequilibrium over anonymous genome regions.
    Hum Mol Genet. 1995 May;4(5):887-94 PMID: 7633449
  38. Characterization of an unusual DNA length polymorphism 5' to the human antithrombin III gene.
    Nucleic Acids Res. 1983 Dec 20;11(24):8569-82 PMID: 6672771
  39. Genetic polymorphisms and disease.
    N Engl J Med. 1998 May 28;338(22):1626 PMID: 9606122
  40. Caucasian genes in American blacks: new data.
    Am J Hum Genet. 1992 Jan;50(1):145-55 PMID: 1729885
  41. Selected public health observations derived from Multicenter AIDS Cohort Study.
    J Acquir Immune Defic Syndr. 1988;1(1):2-7 PMID: 3063804
  42. A scan for linkage disequilibrium across the human genome.
    Genetics. 1999 Aug;152(4):1711-22 PMID: 10430595
  43. Human antithrombin II (AT3) gene length polymorphism revealed by the polymerase chain reaction.
    Nucleic Acids Res. 1989 Aug 11;17(15):6433 PMID: 2771663
Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/302820
Published
2000-03-00
Pages
969-78
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1288177
Subset
IM
Grants
NCI NIH HHS · N01-CO-56000 · United States
External Links
PubMed source DOI: 10.1086/302820 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2