Summary
Linkage analysis has been successful in identifying the genetic basis of numerous Mendelian diseases. These successes were due in part to the rapid developments in molecular biology, which have yielded a plethora of informative genetic markers. Although there is strong evidence that the manifestation of schizophrenia and bipolar affective disorders is controlled by genes, no evidence for linkage has been established. For psychiatric disorders, the most important limiting factor is likely to be the lack of single loci with very large effects that occur with any relevant frequency. The difficulties of linkage studies in psychiatric disorders are discussed with reference to non-psychiatric genetic diseases for which linkage to genetic markers has been successful. Recommendations for collecting information to clarify the patterns of transmission of the psychiatric disorders are described.
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References
Barbosa J, King R, Noreen H, Yunis EJ (1977) The histocompatibility (HLA) system in juvenile insulin-dependent diabetic multiplex kindreds. J Clin Invest 60:989–998
Barbosa J, Chern MM, Anderson VE, et al (1980) Linkage analysis between the major histocompatibility system (HLA) and insulin dependent diabetes in families with patients in two consecutive generations. J Clin Invest 65:592–601
Beaudet A, Bowcock A, Buchwald M, et al (1986) Linkage of cystic fibrosis to two tightly linked DNA markers: Joint report from a collaborative study. Am J Hum Genet 39:681–693
Bell GI, Xiang K, Newman MV, et al (1991) Gene for non-insulin dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 2q. Proc Natl Acad Sci USA 88:1484–1488
Bishop DT, Cannon-Albright L, McLellan T, et al (1988) Segregation and linkage analyis of nine Utah breast cancer pedigrees. Genet Epidemiol 5:151–169
Claus EB, Risch N, Thompson WD (1990) Age of onset as an indicator of familial risk of breast cancer. Am J Epidemiol 131:961–972
Claus EB, Risch N, Thompson WD (1991) Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 48:232–242
Easton DF, Bishop DT, Ford D, Crockford GP, and the Breast Cancer Linkage Consortium (1993) Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am J Hum Genet 52:678–701
Fajans SS (1990) Scope and heterogeneous nature of MODY. Diabetes Care 13:49–64
Froguel PH, Vaxillaire M, Sun F, et al (1992) Close linkage of glucokinase locus on chromosome 7p to early onset non-insulin-dependent diabetes mellitus. Nature 356:162–164
Goate AM, Hayns AR, Owen MJ, et al (1989) Predisposing locus for Alzheimer's disease on chromosome 21. Lancet 1:352–355
Gusella JF, Wexler NS, Conneally PM, et al (1983) A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306:234–238
Hall JM, Lee MK, Newman B, et al (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250:1684–1689
Kinzler KW, Nilbert MC, Li-Kuo S, et al (1991) Identifikation of FAP Locus Genes from Chromosome 5q21. Science 253:661–665
Kunkel LM, et al (1986) Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature 322:73–77
McKusick VC (1990) Mendelian Inheritance in Man, Ninth Edition. The Johns Hopkins University Press, Baltimore
Merikangas KR (1987) Genetic epidemiology of psychiatric disorders. In: Frances AJ, Hales RE (eds) American psychiatric association annual review, vol 6. Psychiatry update. American Psychiatric Press, Washington, DC
Newman B, Austin MA, Lee M, King MC (1988) Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families. Proc Nacl Acad Sci USA 85:1–5
Nishisho I, Nakamura Y, Miyoshi Y, et al (1991) Mutations of Chromosome 5q21 Genes in FAP and Colorectal Cancer Patients. Science 253:665–669
Peltomäki P, Aaltonen LA, Sistronen P, Pylkkänen L, Mecklin JP, Järvinen H, Green JS, Jass JR, Weber JL, Leach FS, Petersen GM, Hamilton SR, Chapelle A de la, Vogelstein B (1993) Genetic Mapping of a Locus Predisposing to Human Colorectal Cancer. Science, 260:810
Risch SS (1990) Mapping genes in diabetes: genetic epidemiological perspective. Diabetes 39:1315–1319
Risch N (1987) Assessing the role of HLA-linked and unlinked determinants of disease. Am J Hum Genet 40:1–14
Risch N (1990a) Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet 46:222–228
Risch N (1990b) Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am J Hum Genet 46:229–241
Risch N, Ghosh S, Todd J (1993) Statistical evaluation of multiple locus linkage data in experimental species and relevance to human studies: application to NOD in mouse and human IDDM Am J Hum Genet (in press)
Schellenberg GD, Bird TD, Wijsman EM, et al (1988) Absence of linkage of chromosome 21q21 markers of familial Alzheimer's disease. Science 241:1507–1510
Schellenberg G, et al (1992) Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14. Science 258:668–671
Schwartz AG, King MC, Belle SH, et al (1985) Risk of breast cancer to relatives of young breast cancer patients. J Natl Cancer Inst 75:665–668
St. George-Hyslop PH, Tanzi RH, Polinsky RJ, et al (1987) The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science 235:885–890
Todd JA, Aitman TJ, Cornall RJ, et al (1991) Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature 351:542–547
Willams WR, Anderson DE (1984) Genetic epidemiology of breast cancer: segregation analysis of 200 Danish pedigrees. Genet Epidemiol 1:7–20
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Risch, N., Merikangas, K.R. Linkage studies of psychiatric disorders. Eur Arch Psychiatry Clin Nuerosci 243, 143–149 (1993). https://doi.org/10.1007/BF02190720
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DOI: https://doi.org/10.1007/BF02190720