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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Linkage Disequilibrium

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Disease relevance of Linkage Disequilibrium


Psychiatry related information on Linkage Disequilibrium


High impact information on Linkage Disequilibrium


Chemical compound and disease context of Linkage Disequilibrium


Biological context of Linkage Disequilibrium

  • Using fine-mapping based on linkage disequilibrium in North African inbred families, we identified a short ancestral haplotype on chromosome 12q13 (<1 cM), sequenced a BAC contig encompassing the triple-A minimal region and identified a novel gene (AAAS) encoding a protein of 547 amino acids that is mutant in affected individuals [19].
  • DTD maps to distal chromosome 5q and, based on linkage disequilibrium studies in the Finnish population, we had previously predicted that the DTD gene should lie about 64 kb away from the CSF1R locus [20].
  • Direct hybridization analysis of the point mutation using a specific oligonucleotide probe demonstrated that this mutation is also in linkage disequilibrium with RFLP haplotype 2 alleles that make up about 20% of mutant PAH genes [21].
  • It has been difficult to identify the precise MHC genes associated with infection and autoimmunity, mainly because of the strong linkage disequilibrium over the region [22].
  • In this study, we describe three novel intron 1 SNPs, and, together with the coding SNP haplotypes, the data suggest the presence of distinct ancestral haplotypes for HSCR and sporadic MTC in linkage disequilibrium with a putative founding susceptibility locus/loci [23].

Anatomical context of Linkage Disequilibrium


Associations of Linkage Disequilibrium with chemical compounds


Gene context of Linkage Disequilibrium

  • The zone of linkage disequilibrium is flanked by the i97 locus, positioned 30 kb proximal to i82, and the HLA-F gene, found 250 kb distal to HLA-A, markers of which display no significant association with HFE [34].
  • This low level of recombination contributes to the unusually broad region of linkage disequilibrium found with hh [35].
  • Furthermore, the expanded sample yielded a sharp peak of evidence for linkage disequilibrium that spanned approximately 170 kb and that was centered 100 kb telomeric to HLA-C [36].
  • Here we present the results of a search for a region that exhibits linkage disequilibrium with the disorder, under the assumption that identification of such a region may provide an alternative method of narrowing down the location of WRN, the gene responsible for WS [37].
  • Characterization of associations between polymorphic sites located throughout the approximately 200-400-kb variable-length region spanning RNU2-BRCA1 reveals nearly complete linkage disequilibrium [38].

Analytical, diagnostic and therapeutic context of Linkage Disequilibrium


  1. A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Lang, H.L., Jacobsen, H., Ikemizu, S., Andersson, C., Harlos, K., Madsen, L., Hjorth, P., Sondergaard, L., Svejgaard, A., Wucherpfennig, K., Stuart, D.I., Bell, J.I., Jones, E.Y., Fugger, L. Nat. Immunol. (2002) [Pubmed]
  2. Association of class II human histocompatibility leukocyte antigens with rheumatic fever. Ayoub, E.M., Barrett, D.J., Maclaren, N.K., Krischer, J.P. J. Clin. Invest. (1986) [Pubmed]
  3. HLA-linked genetic control of host response to Mycobacterium leprae. de Vries, R.R., Fat, R.F., Nijenhuis, L.E., van Rood, J.J. Lancet (1976) [Pubmed]
  4. Linkage disequilibrium in the insulin gene region: size variation at the 5' flanking polymorphism and bimodality among "class I" alleles. McGinnis, R.E., Spielman, R.S. Am. J. Hum. Genet. (1994) [Pubmed]
  5. Family-based analysis using a dense single-nucleotide polymorphism-based map defines genetic variation at PSORS1, the major psoriasis-susceptibility locus. Veal, C.D., Capon, F., Allen, M.H., Heath, E.K., Evans, J.C., Jones, A., Patel, S., Burden, D., Tillman, D., Barker, J.N., Trembath, R.C. Am. J. Hum. Genet. (2002) [Pubmed]
  6. Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers. Cook, E.H., Courchesne, R.Y., Cox, N.J., Lord, C., Gonen, D., Guter, S.J., Lincoln, A., Nix, K., Haas, R., Leventhal, B.L., Courchesne, E. Am. J. Hum. Genet. (1998) [Pubmed]
  7. Nonreplication of linkage disequilibrium between the dopamine D4 receptor locus and Tourette syndrome. Hebebrand, J., Nöthen, M.M., Ziegler, A., Klug, B., Neidt, H., Eggermann, K., Lehmkuhl, G., Poustka, F., Schmidt, M.H., Propping, P., Remschmidt, H. Am. J. Hum. Genet. (1997) [Pubmed]
  8. Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43. Parvari, R., Hershkovitz, E., Kanis, A., Gorodischer, R., Shalitin, S., Sheffield, V.C., Carmi, R. Am. J. Hum. Genet. (1998) [Pubmed]
  9. Are the associations between Alzheimer's disease and polymorphisms in the apolipoprotein E and the apolipoprotein CII genes due to linkage disequilibrium? Tsuda, T., Lopez, R., Rogaeva, E.A., Freedman, M., Rogaev, E., Drachman, D., Pollen, D., Haines, J., Liang, Y., McLachlan, D.R. Ann. Neurol. (1994) [Pubmed]
  10. Tyrosine hydroxylase gene in linkage disequilibrium with mood disorders. Serretti, A., Macciardi, F., Cusin, C., Verga, M., Pedrini, S., Smeraldi, E. Mol. Psychiatry (1998) [Pubmed]
  11. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Suzuki, A., Yamada, R., Chang, X., Tokuhiro, S., Sawada, T., Suzuki, M., Nagasaki, M., Nakayama-Hamada, M., Kawaida, R., Ono, M., Ohtsuki, M., Furukawa, H., Yoshino, S., Yukioka, M., Tohma, S., Matsubara, T., Wakitani, S., Teshima, R., Nishioka, Y., Sekine, A., Iida, A., Takahashi, A., Tsunoda, T., Nakamura, Y., Yamamoto, K. Nat. Genet. (2003) [Pubmed]
  12. Crossover clustering and rapid decay of linkage disequilibrium in the Xp/Yp pseudoautosomal gene SHOX. May, C.A., Shone, A.C., Kalaydjieva, L., Sajantila, A., Jeffreys, A.J. Nat. Genet. (2002) [Pubmed]
  13. Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Morahan, G., Huang, D., Ymer, S.I., Cancilla, M.R., Stephen, K., Dabadghao, P., Werther, G., Tait, B.D., Harrison, L.C., Colman, P.G. Nat. Genet. (2001) [Pubmed]
  14. Ataxia with vitamin E deficiency: refinement of genetic localization and analysis of linkage disequilibrium by using new markers in 14 families. Doerflinger, N., Linder, C., Ouahchi, K., Gyapay, G., Weissenbach, J., Le Paslier, D., Rigault, P., Belal, S., Ben Hamida, C., Hentati, F. Am. J. Hum. Genet. (1995) [Pubmed]
  15. D2 receptors binding potential is not affected by Taq1 polymorphism at the D2 receptor gene. Laruelle, M., Gelernter, J., Innis, R.B. Mol. Psychiatry (1998) [Pubmed]
  16. Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. McDougle, C.J., Epperson, C.N., Price, L.H., Gelernter, J. Mol. Psychiatry (1998) [Pubmed]
  17. C4A gene deletion: association with Graves' disease. Ratanachaiyavong, S., Lloyd, L., McGregor, A.M. J. Mol. Endocrinol. (1989) [Pubmed]
  18. Apolipoprotein B gene polymorphisms are associated with lipid levels in men of South Asian descent. Renges, H.H., Wile, D.B., McKeigue, P.M., Marmot, M.G., Humphries, S.E. Atherosclerosis (1991) [Pubmed]
  19. Mutant WD-repeat protein in triple-A syndrome. Tullio-Pelet, A., Salomon, R., Hadj-Rabia, S., Mugnier, C., de Laet, M.H., Chaouachi, B., Bakiri, F., Brottier, P., Cattolico, L., Penet, C., Bégeot, M., Naville, D., Nicolino, M., Chaussain, J.L., Weissenbach, J., Munnich, A., Lyonnet, S. Nat. Genet. (2000) [Pubmed]
  20. The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping. Hästbacka, J., de la Chapelle, A., Mahtani, M.M., Clines, G., Reeve-Daly, M.P., Daly, M., Hamilton, B.A., Kusumi, K., Trivedi, B., Weaver, A. Cell (1994) [Pubmed]
  21. An amino-acid substitution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2. DiLella, A.G., Marvit, J., Brayton, K., Woo, S.L. Nature (1987) [Pubmed]
  22. HLA genomics in the third millennium. Trowsdale, J. Curr. Opin. Immunol. (2005) [Pubmed]
  23. A founding locus within the RET proto-oncogene may account for a large proportion of apparently sporadic Hirschsprung disease and a subset of cases of sporadic medullary thyroid carcinoma. Borrego, S., Wright, F.A., Fernández, R.M., Williams, N., López-Alonso, M., Davuluri, R., Antiñolo, G., Eng, C. Am. J. Hum. Genet. (2003) [Pubmed]
  24. Sequence variation and linkage disequilibrium in the human T-cell receptor beta (TCRB) locus. Subrahmanyan, L., Eberle, M.A., Clark, A.G., Kruglyak, L., Nickerson, D.A. Am. J. Hum. Genet. (2001) [Pubmed]
  25. Premature telomeric loss in rheumatoid arthritis is genetically determined and involves both myeloid and lymphoid cell lineages. Schönland, S.O., Lopez, C., Widmann, T., Zimmer, J., Bryl, E., Goronzy, J.J., Weyand, C.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  26. HLA-B18 is associated with decreased levels of isoproterenol-stimulated cAMP in lymphocytes. Erickson, R.P., Pairitz, G.L., Karolyi, J.M., Kapur, J.J., Odenheimer, D.J., Schultz, J.S., Sing, C.F. Am. J. Hum. Genet. (1985) [Pubmed]
  27. Analysis of genetic variation reveals human immunoglobulin VH-region gene organization. Walter, M.A., Cox, D.W. Am. J. Hum. Genet. (1988) [Pubmed]
  28. Population frequencies and putative haplotypes of the killer cell immunoglobulin-like receptor sequences and evidence for recombination. Witt, C.S., Dewing, C., Sayer, D.C., Uhrberg, M., Parham, P., Christiansen, F.T. Transplantation (1999) [Pubmed]
  29. Influence of allelic polymorphism on the assembly and surface expression of class II MHC (Ia) molecules. Germain, R.N., Bentley, D.M., Quill, H. Cell (1985) [Pubmed]
  30. Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes. Garin, M.C., James, R.W., Dussoix, P., Blanché, H., Passa, P., Froguel, P., Ruiz, J. J. Clin. Invest. (1997) [Pubmed]
  31. Contrasting effects of selection on sequence diversity and linkage disequilibrium at two phytoene synthase loci. Palaisa, K.A., Morgante, M., Williams, M., Rafalski, A. Plant Cell (2003) [Pubmed]
  32. The structure of linkage disequilibrium at the DBH locus strongly influences the magnitude of association between diallelic markers and plasma dopamine beta-hydroxylase activity. Zabetian, C.P., Buxbaum, S.G., Elston, R.C., Köhnke, M.D., Anderson, G.M., Gelernter, J., Cubells, J.F. Am. J. Hum. Genet. (2003) [Pubmed]
  33. Evidence, from family studies, for linkage disequilibrium between TGFA and a gene for nonsyndromic cleft lip with or without cleft palate. Feng, H., Sassani, R., Bartlett, S.P., Lee, A., Hecht, J.T., Malcolm, S., Winter, R.M., Vintiner, G.M., Buetow, K.H., Gasser, D.L. Am. J. Hum. Genet. (1994) [Pubmed]
  34. Anonymous marker loci within 400 kb of HLA-A generate haplotypes in linkage disequilibrium with the hemochromatosis gene (HFE). Yaouanq, J., Perichon, M., Chorney, M., Pontarotti, P., Le Treut, A., el Kahloun, A., Mauvieux, V., Blayau, M., Jouanolle, A.M., Chauvel, B. Am. J. Hum. Genet. (1994) [Pubmed]
  35. Haplotype analysis of hemochromatosis: evaluation of different linkage-disequilibrium approaches and evolution of disease chromosomes. Ajioka, R.S., Jorde, L.B., Gruen, J.R., Yu, P., Dimitrova, D., Barrow, J., Radisky, E., Edwards, C.Q., Griffen, L.M., Kushner, J.P. Am. J. Hum. Genet. (1997) [Pubmed]
  36. Localization of psoriasis-susceptibility locus PSORS1 to a 60-kb interval telomeric to HLA-C. Nair, R.P., Stuart, P., Henseler, T., Jenisch, S., Chia, N.V., Westphal, E., Schork, N.J., Kim, J., Lim, H.W., Christophers, E., Voorhees, J.J., Elder, J.T. Am. J. Hum. Genet. (2000) [Pubmed]
  37. Linkage disequilibrium and haplotype studies of chromosome 8p 11.1-21.1 markers and Werner syndrome. Yu, C.E., Oshima, J., Goddard, K.A., Miki, T., Nakura, J., Ogihara, T., Poot, M., Hoehn, H., Fraccaro, M., Piussan, C. Am. J. Hum. Genet. (1994) [Pubmed]
  38. Evidence for effective suppression of recombination in the chromosome 17q21 segment spanning RNU2-BRCA1. Liu, X., Barker, D.F. Am. J. Hum. Genet. (1999) [Pubmed]
  39. Linkage disequilibrium, cystic fibrosis, and genetic counseling. Beaudet, A.L., Feldman, G.L., Fernbach, S.D., Buffone, G.J., O'Brien, W.E. Am. J. Hum. Genet. (1989) [Pubmed]
  40. Linkage disequilibrium predicts physical distance in the adenomatous polyposis coli region. Jorde, L.B., Watkins, W.S., Carlson, M., Groden, J., Albertsen, H., Thliveris, A., Leppert, M. Am. J. Hum. Genet. (1994) [Pubmed]
  41. Is there a genetic susceptibility locus for Parkinson's disease on chromosome 22q13? Wilhelmsen, K., Mirel, D., Marder, K., Bernstein, M., Naini, A., Leal, S.M., Cote, L.J., Tang, M.X., Freyer, G., Graziano, J., Mayeux, R. Ann. Neurol. (1997) [Pubmed]
  42. Association of amino acid variants in the activating transcription factor 6 gene (ATF6) on 1q21-q23 with type 2 diabetes in Pima Indians. Thameem, F., Farook, V.S., Bogardus, C., Prochazka, M. Diabetes (2006) [Pubmed]
  43. Loss of HLA haplotype and B locus down-regulation in melanoma cell lines. Marincola, F.M., Shamamian, P., Alexander, R.B., Gnarra, J.R., Turetskaya, R.L., Nedospasov, S.A., Simonis, T.B., Taubenberger, J.K., Yannelli, J., Mixon, A. J. Immunol. (1994) [Pubmed]
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