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Sampling strategies for linkage studies

  • Molecular Genetics of Schizophrenia
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Summary

Broadly there are three alternative sampling strategies for linkage studies of complex disorders such as schizophrenia. These are to select either affected sib pairs (and their parents) or small-to-medium-size pedigrees, or large pedigrees. The advantages and disadvantages of each are discussed. Our studies show that, even in the presence of heterogeneity, linkage can be found in clinically realistic sample sizes of nuclear families or medium-sized pedigrees. However, relying on affected sib pair methods in less satisfactory.

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References

  • Baron M, Risch N, Hamburger R, Mandel B, Kushner S, Newman M, Drumer D, Belmaker RH (1987) Genetic linkage between X-chromosome markers and bipolar affective illness. Nature 326:289–292

    Google Scholar 

  • Berrettini WH, Goldin LR, Gelernter J, Gejman PV, Gershon ES, Detera-Wadleigh S (1990) X-chromosome markers and manic depressive illness; rejection of linkage to Xq28 in nine bipolar pedigrees. Arch Gen Psychiatry 47:366–373

    Google Scholar 

  • Blackwelder WC, Elston RC (1985) A comparison of sib-pair linkage tests for disease susceptibility loci. Genet Epidemiol 2:85–97

    Google Scholar 

  • Cavalli-Sforza LL, King MC (1986) Detecting linkage for genetically heterogeneous diseases and detecting heterogeneity with linkage data. Am J Hum Genet 38:599–616

    Google Scholar 

  • Chakravarti A, Badner JA, Li CC (1987) Tests of linkage and heterogeneity in mendelian diseases using identity by descent scores. Genet Epidemiol 4:255–266

    Google Scholar 

  • Clerget-Darpoux F, Babron MC, Bonaiti-Pellie C (1987) Power and robustness of the linkage homogeneity test in genetic analysis of common disorders. J Psychiatr Res 21:625–630

    Google Scholar 

  • Detera-Wadleigh SD, Berrettini WH, Goldin LR, Boorman D, Anderson S, Gershon ES (1987) Close linkage of c-Harveyras-1 and the insulin gene to affective disorder is ruled out in three North American pedigrees. Nature 326:289–292

    Google Scholar 

  • Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK, Allen CR, Hostetter AM, Housman DE (1987) Bipolar affective disorders linked to DNA markers on chromosome 11. Nature 325:783–787

    Google Scholar 

  • Goldin LR, Gershon ES (1988) The power of affected-sib-pair method for heterogeneous disorders. Genet Epidemiol 5:35–43

    Google Scholar 

  • Lander ES, Botstein D (1986) Strategies for studying heterogeneous genetic traits in humans by using a linkage map of restriction fragment lengh polymorphisms. Proc Natl Acad Sci USA 83:7753–7757

    Google Scholar 

  • Lathrop GM, Lalouel JM, Julier C, Ott J (1984) Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 81:3443–3446

    Google Scholar 

  • Martinez M, Goldin LR (1989) The detection of linkage and heterogeneity in nuclear families for complex disorders: one vs. two marker loci. Am J Hum Genet 44:552–559

    Google Scholar 

  • Martinez M, Goldin LR (1990) Power of the linkage test for a heterogeneous disorder due to two independent inherited causes: A simulation study. Genet Epidemiol 7:219–230

    Google Scholar 

  • Nurnberger JI Jr, Goldin LR, Gershon ES (1986) Genetics of psychiatric disorders. In: Winokur G, Clayton P (eds) The Medical basis of psychiatry. Saunders, Philadelphia, pp 486–521

    Google Scholar 

  • Ott J (1986) The number of families required to detect or exclude linkage heterogeneity. Am J Hum Genet 39:159–165

    Google Scholar 

  • Penrose LS (1935) The detection of autosomal linkage in data which consists of pairs of brother and sisters of unspecified parentage. Ann Eugen 6:133–138

    Google Scholar 

  • Penrose LS (1953) The general purpose sib-pair linkage test. Ann Eugen 18:120–124

    Google Scholar 

  • Sherrington R, Brynjolfsson J, Petursson H, Potter M, Dudleston K, Barraclough B, wasmuth J, Dobbs M, Gurling H (1988) Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature 336:164–167

    Google Scholar 

  • Smith CAB (1963) Testing for heterogeneity of recombination fraction values in human genetics. Ann Hum Genet 27:175–182

    Google Scholar 

  • Suarez BK, Rice J, Reich T (1978) The generalized sib pair IBD distribution: its use in the detection of linkage. Ann Hum Genet 42:87–94

    Google Scholar 

  • Thomson G, Bodmer WF (1977) The genetics of HLA and disease associations. In: Christiansen FB, Fenchal R, Barndorff-Nielson O (eds) Measuring selection in natural populations. Springer, Berlin Heidelberg New York, pp 545–564

    Google Scholar 

  • Thomson G (1988) HLA disease associations: models for insulin dependent diabetes mellitus and the study of complex human genetic disorders. Ann Rev Genet 22:31–50

    Google Scholar 

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Goldin, L.R., Martinez, M.M. & Gershon, E.S. Sampling strategies for linkage studies. Eur Arch Psychiatry Clin Nuerosci 240, 182–187 (1991). https://doi.org/10.1007/BF02190761

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