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The Identification of Genes for Complex Genetic Diseases

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Genomes

Part of the book series: Stadler Genetics Symposia Series ((SGSS))

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Abstract

The identification of genes that are involved in complex genetic diseases remains a difficult task for researchers in the field of human genetics. While genes involved in a wide array of Mendelian disorders have been identified, the same approaches are not necessarily suitable for diseases that involve several genes and/or environmental influences. We have used the direct analysis of candidate gene loci, in which there was compelling biological evidence for involvement in the disease, to identify loci that play a role in HIV infection, development of AIDS, and age-related macular degeneration.

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References

  • Alkhatib, G., Combadiere, C., Broder, C.C., Feng, Y., Kennedy, P.E., Murphy, P.M., and Berger, E.A., 1996, CC CKR5: A RANTES, MIP-1, MIP-1 receptor as a fusion cofactor for macrophage-tropic HIV-1, Science 272:1955–1958.

    Article  PubMed  CAS  Google Scholar 

  • Allikmets, R., Shroyer, N.F., Singh, N., Seddon, J.M., Lewis, R.A., Bernstein, P.S., Peiffer, A., Zabriskie, N.A., Li, Y., Hutchinson, A., Dean, M., Lupski, J.R., and Leppert, M., 1997b, Mutation of the Stargardt Disease Gene (ABCR) in Age-Related Macular Degeneration, Science 277:1805–1807.

    Article  PubMed  CAS  Google Scholar 

  • Allikmets, R., Singh, N., Sun, H., Shroyer, N.F., Hutchinson, A., Chidambaram, A., Gerrard, B., Baird, L., Stauffer, D., Peiffer, A., Rattner, A., Smallwood, P., Li, Y., Anderson, K.L., Lewis, R.A., Nathans, J., Leppert, M., Dean, M., and Lupski, J.R., 1997a, A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy, Nature Genetics 15:236–246.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, K.L., Baird, L., Lewis, R.A., Chinault, A.C., Otterud, B., Leppert, M., and Lupski, J.R.A., 1995, YAC contig encompassing the recessive Stargardt disease gene (STGD) on chromosome lp, American Journal of Human Genetics 57:1351–1363.

    PubMed  CAS  Google Scholar 

  • Baier, M., Werner, A., Bannert, N., Metzner, K., and Kurth, R., 1995, HIV suppression by interleukin-16, Nature 378(6557):563.

    Article  PubMed  CAS  Google Scholar 

  • Buchbinder, S.P., Katz, M.H., Hessol, N.A., O’Malley, P.M., and Holmberg, S. D., 1994, Long-term HIV-1 infection without immunologie progression. AIDS 8(8):1123–1128.

    Article  PubMed  CAS  Google Scholar 

  • Cairns J.S., and D’Souza M.P., 1998, Chemokines and HIV-1 second receptors: The therapeutic connection. Nature Medicine 4:563–568.

    Article  PubMed  CAS  Google Scholar 

  • Cann, R.L., Stoneking, M., and Wilson, A.C., 1987, Mitochondrial DNA and human evolution, Nature 325(6099):31–36.

    Article  PubMed  CAS  Google Scholar 

  • Chakraborty, R., and Smouse, P.E., 1988, Recombination of haplotypes leads to biased estimates of admixture proportions in human populations, Proc. Natl. Acad. Sci. (USA) 85(9):3071–3074.

    Article  PubMed  CAS  Google Scholar 

  • Choe, H., Farzan, M., Sun, Y., Sullivan, N., Rollins, B., Ponath, P.D., Wu, L., Mackay, C.R., LaRosa, G., Newman, W., Gerard, N., Gerard, C., and Sodroski, J., 1996, The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates, Cell 85(7):1135–1148.

    Article  PubMed  CAS  Google Scholar 

  • Cocchi, F., DeVico, A.L., Garzino-Demo, A., Arya, S. K., Gallo, R.C., and Lusso, P., 1995, Identification of RANTES, MIP-1, and MIP-1 as the major HIV-suppressive factors produced by CD8+ T cells. Science 270:1811–1815.

    Article  PubMed  CAS  Google Scholar 

  • Coffin, J., 1995, HIV population dynamics in vivo; implications for genetic variation, pathogenesis, and therapy, Science 267:483–489.

    Article  PubMed  CAS  Google Scholar 

  • Combadiere, C., Ahuja, S.K., Tiffany, H.L., and Murphy, P.M.. 1996, Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MlP-l(alpha), MlP-l(beta), and RANTES, J. Leukocyte Biology 60(1):147–152.

    CAS  Google Scholar 

  • Dean, M., Stephens, J.C., Winkler, C., Lomb, D.A., Ramsburg, M., Boaze, R., Stewart, C., Charbonneau, L., Goldman, D., and Albaugh, B. J., 1994, Polymorphic admixture typing in human ethnic populations, Am. J. Hum. Genet. 55(4):788–808.

    PubMed  CAS  Google Scholar 

  • Dean, M., Carrington, M., Winkler, C., Huttley, G.A., Smith, M.W., Allikmets, R., Goedert, J.J., Buchbinder, S.P., Vittinghoff, E., Gomperts, E., Donfield, S., Vlahov, D., Kaslow, R., Saah, A., Rinaldo, C., Detels, R., and O’Brien, S.J., 1996, Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene, Science 273:1856–1862.

    Article  PubMed  CAS  Google Scholar 

  • Delwart, E.L., Shpaer, E.G., Louwagie, J., McCutchan, F.E., Grez, M., Rubsamen-Waigmann, H., and Mullins, J.I., 1993, Genetic relationships determined by a DNA heteroduplex mobility assay: analysis of HIV-1 env genes. Science 262(5137):1257–1261.

    Article  PubMed  CAS  Google Scholar 

  • Deng, H., Liu, R., Elllmeier, W., Choe, S., Unutmaz, D., Burkhart, M., DiMarzio, P., Marmon, S., Sutton, R.E., Hill, CM., Davis, C.B., Peiper, S.C., Schall, T.J., Littman, D.R., and Landau, N.R., 1996, Identification of a major co-receptor for primary isolates of HIV-1, Nature 381(6584):661–666.

    Article  PubMed  CAS  Google Scholar 

  • Detels, R., Liu, Z., Hennessey, K., Kan, J., Visscher, B.R., Taylor, J.M., Hoover, D.R., Rinaldo, C.R. Jr., Phair, J.P., and Saah, A.J., 1996, Resistance to HIV-1 infection. Multicenter AIDS cohort study, J. AIDS 7(12):1263–1269.

    Google Scholar 

  • Detels, R., Mann, D., Carrington, M., Hennessey, K., Wu, Z., Hirji, K.F., Wiley, D., Visscher, B.R., and Giorgi, J.V., 1996, Resistance to HIV infection may be genetically mediated, J. AIDS 10(1):102–104.

    Article  CAS  Google Scholar 

  • Doranz, B. J., Rucker, J., Yi, Y., Smyth, R.J., Samson, M., Peiper, S.C., Parmentier, M., Collman, R.G., and Doms, R.W., 1996, A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors, Cell 85(7):1149–1158.

    Article  PubMed  CAS  Google Scholar 

  • Dragic, T., Litwin, V., Allaway, G.P., Martin, S.R., Huang, Y., Nagashima, K.A., Cayanan, C., Maddon, P.J., Koup, R.A., Moore, J.P., and Paxton, W.A., 1996, HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5, Nature 381(6584):667.

    Article  PubMed  CAS  Google Scholar 

  • Federsppiel, B., Melhado, IG., Duncan, A.M., Delaney, A., Schappert, K., Clark-Lewis, I., and Jirik, F.R., 1993, Molecular cloning of the cDNA and chromosomal localization of the gene for a putative seven-transmembrane segment (7-TMS) receptor isolated from human spleen, Genomics 16(3):707–712.

    Article  PubMed  CAS  Google Scholar 

  • Feng, Y., Broder, C.C., Kennedy, P.E., and Berger, E.A., 1996, HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor, Science 272:872.

    Article  PubMed  CAS  Google Scholar 

  • Goedert, J.J., Biggar, R.J., Winn, D.M., Mann, D.L., Byar, D.P., Strong, D.M., DiGioia, R.A., Grossman, R.J., Sanchez, W.C., and Kase, R.G., 1985, Decreased helper T lymphocytes in homosexual men. I. Sexual contact in high-incidence areas for the acquired immunodeficiency syndrome, Am. J. Epidemiol. 121(5):629–636.

    Article  PubMed  CAS  Google Scholar 

  • Goedert, J.J., Kessler, CM., Aledort, L.M., Biggar, R.J., Andes, W.A., White, G.C. 2d, Drummond, J.E., Vaidya, K., Mann, D.L., and Eyster, M.E., 1989, A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia, N. Engl. J. Med. 321(17):1141–1148.

    Article  PubMed  CAS  Google Scholar 

  • Haynes, B.F., Pantaleo, G., and Fauci, A.S., 1996, Toward an understanding of the correlates of protective immunity to HIV infection, Science 271(5247):324–328.

    Article  PubMed  CAS  Google Scholar 

  • Herzog, H., Hort, Y.J., Shine, J., and Selbie, L.A., 1993, Molecular cloning, characterization, and localization of the human homolog to the reported bovine NPY Y3 receptor: lack of NPY binding and activation, DNA and Cell Biology 12(6):465–471.

    Article  PubMed  CAS  Google Scholar 

  • Hilgartner, M.W., Donfield, S.M., Willoughby, A., Contant, CF. Jr., Evatt, B.L., Gomperts, E.D., Hoots, W.K., Jason, J., Loveland, K.A., and McKinlay, S.M., 1993, Hemophilia growth and development study. Design, methods, and entry data, Am. J. Pediatr. Hematol Oncol 15(2):208–218.

    Article  PubMed  CAS  Google Scholar 

  • Kaslow, R. A., Ostrow, D.G., Detels, R., Phair, J.P., Polk, B.F., and Rinaldo, C.R. Jr., 1987, The multicenter AIDS cohort study: rationale, organization, and selected characteristics of the participants, Am. J. Epidemiol. 126(2):310–318.

    Article  PubMed  CAS  Google Scholar 

  • Kaslow, R.A., Carrington, M., Apple, R., Park, L., Munoz, A., Saah, A.J., Goedert, J.J., Winkler, C., O’Brien, S.J., Rinaldo, C., Detels, R., Blattner, W., Phair, J., Erlich, H., and Mann, D.L., 1996, Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection, Nature Medicine 2:405–411.

    Article  PubMed  CAS  Google Scholar 

  • Liu R., Paxton, W.A., Choe, S., Ceradini, D., Martin, S.R., Horuk, R., MacDonald, M.E., Stuhlmann, H., Koup, R.A., and Landau, N.R., 1996, Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection, Cell 86(3):367–377.

    Article  PubMed  CAS  Google Scholar 

  • Maddon, P.J., Dalgleish, A.G., McDougal, J.S., Clapham, P.R., Weiss, R.A., and Axel, R., 1986, The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain, Cell 47:333–348.

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Mir, A., Bayes, M., Vilageliu, L., Grinberg, D., Ayugo, C., del Rio, T., Garcia-Sandoval, B., Bussaglia, E., Baiget, M., Gonzalez-Duarte, R., and Balcells, S., 1997, A new locus for autosomal recessive retinitis pigmentosa (RP19) maps tolpl3-lp21, Genomics 40(1):142–146.

    Article  PubMed  CAS  Google Scholar 

  • May, R., and Anderson, R., 1995, Infectious Disease in Humans, Oxford University Press.

    Google Scholar 

  • Mellors, J.W., Rinaldo, C.R. Jr, Gupta, P., White, R.M., Todd, J.A., and Kingsley, L.A., 1996, Prognosis in HIV-1 infection predicted by the quantity of virus in plasma, Science 272(5265):1167–1170.

    Article  PubMed  CAS  Google Scholar 

  • Morb. Mort. Wk. Rep., CDC, 1993, Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Dec. 18, 1992:1–19.

    Google Scholar 

  • ei]Morse, S. S., ed., 1993, Emerging Viruses, Rockefeller University Press, New York, 352 pp.

    Google Scholar 

  • Motulsky, A.G., 1981, Human Genetics: Patterns and Approaches, Springer-Verlag, Berlin.

    Google Scholar 

  • Murphy, P. M., 1994, The molecular biology of leukocyte chemoattractant receptors, Ann. Rev. Immunol. 12:593–633.

    Article  CAS  Google Scholar 

  • Neote, K., DiGregorio, D., Mak, J.Y., Horuk, R., and Schall, T.J., 1993, Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor, Cell 72(3):415–425.

    Article  PubMed  CAS  Google Scholar 

  • Nomura, H., Nielsen, B.W., and Matsushima, K., 1993, Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors, International Immunology 5(10):1239–1249.

    Article  PubMed  CAS  Google Scholar 

  • O’Brien, S.J., 1991, Ghetto legacy. Can the high incidence of Tay-Sachs disease in Ashkenazi Jews be linked to historic epidemics of tuberculosis in industrial European cities? Current Biology 1:209–211.

    Article  PubMed  Google Scholar 

  • O’Brien, T.R., Blattner, W.A., Waters, D., Eyster, E., Hilgartner, M.W., Cohen, A.R., Luban, N., Hatzakis, A., Aledort, L.M., Rosenberg, P.S., Miley, W.J., Kroner, B.L., and Goedert, J.J., 1996, Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study, JAMA 276(2):105–110.

    Article  PubMed  Google Scholar 

  • Orita, M., Suzuki, Y., Sekiua, T., and Hayashi, K., 1989, Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction, Genomics 5(4):874–879.

    Article  PubMed  CAS  Google Scholar 

  • Paxton, W.A., Martin, S.R., Tse, D., OfBrien, T.R., Skurnick, J., VanDevanter, N.L., Padian, N., Braun, J.F., Kotler, D.P., Wolinsky, S.M., and Koup, R.A., 1996, Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure, Nature Medicine 2(4):412–417.

    Article  PubMed  CAS  Google Scholar 

  • Phair, J., Jacobson, L., Detels, R., Rinaldo, C., Saah, A., Schrager, L., and Munoz, A., 1992, Acquired immune deficiency syndrome occurring within 5 years of infection with human immunodeficiency virus type-1: the Multicener AIDS Cohort Study, J. AIDS 5(5):490–496.

    CAS  Google Scholar 

  • Raport, C.J., Schweickart, V.L., Chantry, D., Eddy, R.L. Jr., Shows, T.B., Godiska, R., and Gray, P.W., 1996, New members of the chemokine receptor gene family, J. Leukocyte Biology 59(1):18–23.

    CAS  Google Scholar 

  • Ravnik-Glavac, M., Glavac, D., and Dean, M., 1994, Sensitivity of single-strand conformation polymorphism and heteroduplex method for mutation detection in the cystic fibrosis gene, Hum. Molec. Genet. 3(5):801–807.

    Article  PubMed  CAS  Google Scholar 

  • Samson, M., Labbe, O., Mollereau, C., Vassart, G., and Parmentier, M., 1996, Molecular cloning and functional expression of a new human CC-chemokine receptor gene, Biochemistry 35(11):3362–3367.

    Article  PubMed  CAS  Google Scholar 

  • Samson, M., Libert, F., Doranz, B.J., Rucker, J., Liesnard, C., Farber, CM., Saragosti, S., Lapoumeroulie, C., Cognaux, J., Forceille, C., Muyldermans, G., Verhofstede, C., Burtonboy, G., Georges, M., Imai, T., Rana, S., Yi, Y., Smyth, R.J., Collman, R.G., Doms, R.W., Vassart, G., and Parmentier, M., 1996, Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene, Nature 382(6593):722–725.

    Article  PubMed  CAS  Google Scholar 

  • Sham, P.C., and Curtis, D., 1995, Monte Carlo tests for associations between disease and alleles at highly polymorphic loci, Ann. Hum. Genet. 59(Pt 1):97–105.

    Article  PubMed  CAS  Google Scholar 

  • Sorensen, T.I.A., Nielsen, G.G., Andersen, P.K., and Teasdale, T.W., 1988, Genetic and environmental influences on premature death in adult adoptees, New Engl. J. Med. 318(12):727–732.

    Article  PubMed  CAS  Google Scholar 

  • Stephens, J.C., Briscoe, D., and O’Brien, S.J., 1994, Mapping by admixture linkage disequilibrium in human populations: limits and guidelines, Am. J. Hum. Genet. 55(4):809–824.

    PubMed  CAS  Google Scholar 

  • Vlahov, D., Munoz, A., Anthony, J.C., Cohn, S., Celentano, D.D., and Nelson, K.E., 1990, Association of drug injection patterns with antibody to human immunodeficiency virus type 1 among intravenous drug users in Baltimore, Maryland, Am. J. of Epidemiology 132(5):847–856.

    CAS  Google Scholar 

  • Vlahov, D., Anthony, J.C., Munoz, A., Margolick, J., Nelson, K.E., Celentano, D.D., Solomon, L., and Polk, B.F., 1991, The ALIVE study, a longitudinal study of HIV-1 infection in intravenous drug users: description of methods and characteristics of participants. Department of Epidemiology, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD, NIDA Research Monograph Series 109:75–100.

    CAS  Google Scholar 

  • Wain-Hobson, S., 1993, The fastest genome evolution ever described: HIV variation in situ, Curr. Opin. Genet. Dev. 3(6):878–883.

    Article  PubMed  CAS  Google Scholar 

  • Walter, M.A., Spillett, DJ., Thomas, P., Weissenbach, J., and Goodfellow, P., 1994, A method for constructing radiation hybrid maps of whole genomes, Nature Genet.7(1):22–28.

    Article  PubMed  CAS  Google Scholar 

  • White, M., Carvalho, M., Derse, D., O’Brien, S.J., and Dean, M., 1992, Detecting single base substitutions as heteroduplex polymorphisms, Genomics 12(2):301–306.

    Article  PubMed  CAS  Google Scholar 

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  1. Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD, 21702-1201, USA

    Michael Dean, Rando Allikmets & Mary Carrington

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  1. Michael Dean
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  2. Rando Allikmets
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  3. Mary Carrington
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  1. University of Missouri, Columbia, Missouri, USA

    J. Perry Gustafson

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Dean, M., Allikmets, R., Carrington, M. (2000). The Identification of Genes for Complex Genetic Diseases. In: Gustafson, J.P. (eds) Genomes. Stadler Genetics Symposia Series. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4235-3_3

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  • DOI: https://doi.org/10.1007/978-1-4615-4235-3_3

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