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Chromosomal Aberrations and Schizophrenia

Autosomes

Published online by Cambridge University Press:  02 January 2018

Anne S. Bassett
Anne S. Bassett*
Affiliation:
Department of Psychiatry, University of Toronto; Genetics Section, Schizophrenia Research Program, Queen Street Mental Health Centre
*
∗Queen Street Mental Health Centre, 1001 Queen Street West, Toronto, Ontario M6J 1H4, Canada
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Abstract

Chromosomal aberrations associated with schizophrenic disorders may suggest regions in which to focus a search for genes predisposing to schizophrenia by a linkage strategy. As for other genetic illnesses, chromosomal abnormalities may also provide useful tools for subsequent physical mapping, fine localisation, and isolation of important susceptibility genes. Identification of several chromosomal aberrations may be especially important, given the unknown pathophysiology, the paucity of known brain genes, and the probable genetic heterogeneity of schizophrenia and manic-depression. However, because psychiatric disorders are common and inherited in a complex manner, researchers must use caution when drawing inferences about associations with chromosomal aberrations. Reported abnormalities involving autosomes (chromosomes 1–22) associated with psychotic disorders are reviewed. Their relevance to linkage studies localising genes for schizophrenia was estimated by standardised criteria for specificity, diagnosis, family history, and overall weight of evidence. Four ‘possibly relevant’ chromosomal regions were identified: 5q, 11q, 18q, and 19p. This paper outlines strategies for future studies to detect new chromosomal aberrations associated with major psychotic disorders that may be relevant to isolating the genes for schizophrenia.

Type
Papers
Information
The British Journal of Psychiatry , Volume 161 , Issue 3 , September 1992 , pp. 323 - 334
Copyright
Copyright © 1992 The Royal College of Psychiatrists 

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References

Axelsson, R. & Wahlström, J. (1984) Chromosome aberrations in patients with paranoid psychosis. Hereditas, 100, 29–31.Google Scholar
Ayraud, N., Darcourt, G., Celsnitz, M. D., et al (1969) Syndrome 18p-. Une nouvelle observation. Annates de Génétique, 12, 122–125.Google Scholar
Bassett, A. S. (1989) Chromosome 5 and schizophrenia: implications for linkage studies, current and future. Schizophrenia Bulletin, 15, 393–402.CrossRefGoogle Scholar
Bassett, A. S., McGillivray, B. C., Jones, B. D., et al (1988) Partial trisomy chromosome 5 cosegregating with schizophrenia. Lancet, i, 799–801.CrossRefGoogle Scholar
Berry, A. C., Mutton, D. E. & Lewis, D. G. M. (1978) Mosaicism and the trisomy 8 syndrome. Clinical Genetics, 14, 105–114.Google Scholar
Borgaonkar, D. S. (1989) Chromosomal Variation in Man. New York: Alan R. Liss.Google Scholar
Brzustowicz, L. M., Lehner, T., Castilla, L. H., et al (1990) Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2–13.3. Nature, 344, 540–541.Google Scholar
Byerley, W., Mellon, C. & O'Connell, P. (1989) Mapping genes for manic-depression and schizophrenia with DNA markers. Trends in Neurosciences, 12, 46–48.Google Scholar
Chandley, A. C., Hargreave, T. B., Fletcher, J. M., et al (1980) Trisomy 8: report of a mosaic human male with near-normal phenotype and normal IQ, ascertained through infertility. Human Genetics, 55, 31–38.Google Scholar
Chodirker, B. N., Chudley, A. E., Ray, M., et al (1987) Fragile 19p13 in a family with mental illness. Clinical Genetics, 31, 1–6.CrossRefGoogle Scholar
Christensen, K. R., Friedrich, U., Jacobsen, P., et al (1970) Ring chromosome 18 in mother and daughter. Journal of Mental Deficiency Research, 14, 49–67.Google Scholar
Clark, R. D., Smith, M., Pandolfo, M., et al (1988) Tuberous sclerosis in a liveborn infant with trisomy due to t(11q23.3;22q11.2) translocation (abstract). American Journal of Human Genetics, 43, 44.Google Scholar
Cook, E. H. & Leventhal, B. L. (1987) Down's syndrome and mania. British Journal of Psychiatry, 150, 249–250.CrossRefGoogle ScholarPubMed
Crow, T. J. (1988) Sex chromosomes and psychosis: the case for a pseudoautosomal locus. British Journal of Psychiatry, 153, 675–683.Google Scholar
Dasgupta, J., Dasgupta, D. & Balasubrahmanyan, M. (1973) XXY syndrome XY/XO mosaicism and acentric chromosomal fragments in male schizophrenics. Indian Journal of Medical Research, 61, 62–70.Google Scholar
DeLisi, L. E. & Lovett, M. (1990) The role of molecular genetics in psychiatry: unraveling the etiology for schizophrenia. In Recent Advances in Schizophrenia (eds Kales, A., Stefanis, C. N. & Talbott, J.), pp. 131–161. New York: Springer-Verlag.Google Scholar
Diehl, S. R. & Kendler, K. S. (1989) Strategies for linkage studies of schizophrenia: pedigrees, DNA markers and statistical analyses. Schizophrenia Bulletin, 15, 403–419.Google Scholar
Drouin, R., Messier, P. E. & Richer, C. L. (1988) Human chromosome banding specific for electron microscopy. Cytogenetics and Cell Genetics, 47, 117–120.Google Scholar
El-Badramany, M. H., Farag, T. I., Al-Awadi, S. A., et al (1989) Familial manic-depressive illness with deleted short arm of chromosome 21: coincidental or causal? British Journal of Psychiatry, 155, 856–857.Google Scholar
Escobar, J. I. (1976) A cytogenetic study of children with psychiatric disorders. Comprehensive Psychiatry, 17, 309–313.Google Scholar
Friend, S. H., Bernards, R., Rogelj, S., et al (1986) Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature, 305, 779–784.Google Scholar
Fryer, A. E., Chalmers, A., Connor, J. M., et al (1987) Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet, i, 659–661.CrossRefGoogle Scholar
Gardner, R. J. M. & Sutherland, G. R. (1989) Chromosome Abnormalities and Genetic Counseling. New York: Oxford University Press.Google Scholar
Genest, P., Dumas, L. & Genest, F. B. (1976) Translocation chromosomique t (2; 18) (q21;q23) chez un individu schizophrène et sa fille. L'Union Médicale du Canada, 105, 1676–1681.Google Scholar
Gilliam, T. C., Freimer, N., Powchik, P. P., et al (1989) Characterization of a chromosome 5 deletion hybrid cell line and mapping of markers to a region which cosegregates with schizophrenia. Genomics, 5, 940–944.Google Scholar
Gottesman, I. I. & Shields, J. (1982) Schizophrenia: The Epigenetic Puzzle. Cambridge: Cambridge University Press.Google Scholar
Grandy, K. D., Litt, M., Allen, N., et al (1989) The human dopamine D2 receptor gene is located on chromosome 11 at q22–23 and identifies a Taq 1 RFLP. American Journal of Human Genetics, 45, 778–785.Google Scholar
Green, M. F., Satz, P., Gaier, D. J., et al (1989) Minor physical anomalies in schizophrenia. Schizophrenia Bulletin, 15, 91–99.CrossRefGoogle ScholarPubMed
Guy, J. D., Majorski, L. V., Wallace, C. J., et al (1983) The incidence of minor physical anomalies in adult male schizophrenics. Schizophrenia Bulletin, 9, 571–582.Google Scholar
Hall, J. G. (1990) Genomic imprinting: review and relevance to human diseases. American Journal of Human Genetics, 46, 857–873.Google Scholar
Holland, T. & Gosden, C. (1990) A balanced chromosomal translocation partially co-segregating with psychotic illness in a family. Psychiatry Research, 32, 1–8.CrossRefGoogle ScholarPubMed
Jones, K. L. (1988) Smith's Recognizable Patterns of Human Malformation. Philadelphia: W. B. Saunders.Google Scholar
Kaiser, P. (1984) Pericentric inversions. Problems and significance for clinical genetics. Human Genetics, 68, 1–47.Google Scholar
Kendler, K. S., Gruenberg, A. M. & Tsuang, M. T. (1985) Psychiatric illness in first-degree relatives of schizophrenic and surgical control patients. Archives of General Psychiatry, 42, 770–779.Google Scholar
Kennedy, J. L., Giuffra, L. A., Moises, H. W., et al (1988) Evidence against linkage of schizophrenia to markers on chromosome 5 in a northern Swedish pedigree. Nature, 336, 167–170.Google Scholar
Knoll, J. H. M., Nicholls, R. D., Magenis, R. E., et al (1989) Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. American Journal of Medical Genetics, 32, 285–290.Google Scholar
Krag-Olsen, B., Brask, B. H., Jacobsen, P., et al (1981) Is there an increased risk of psychoses in patients with ring 18 and deletion long arm 18? In Human Behavior and Genetics (eds Schmid, W. & Nielsen, J.), pp. 211–220. Amsterdam: Elsevier/North Holland Biomedical Press.Google Scholar
Krawczun, M. S., Jenkins, E. C. & Brown, W. T. (1985) Analysis of the fragile-X chromosome: localization and detection of the fragile site in high resolution preparations. Human Genetics, 69, 209–211.CrossRefGoogle ScholarPubMed
Ledbetter, D. H., Riccardi, V. M., Airhart, S. D., et al (1981) Deletions of chromosome 15 as a cause of Prader-Willi syndrome. New England Journal of Medicine, 304, 325–329.Google Scholar
Lowing, P. A., Mirsky, A. F. & Pereira, R. (1983) The inheritance of schizophrenia spectrum disorders: a reanalysis of the Danish adoption study data. American Journal of Psychiatry, 140, 1167–1171.Google Scholar
Marden, P. M., Smith, D. W. & McDonald, M. J. (1964) Congenital anomalies in the newborn infant, including minor variations. Journal of Pediatrics, 64, 357.Google Scholar
Mattei, M. G., Souiah, N. & Mattei, J. F. (1984) Chromosome 15 anomalies and the Prader-Willi syndrome: cytogenetic analysis. Human Genetics, 66, 313–334.Google Scholar
McGillivray, B. C., Bassett, A. S., Pantzar, T. P., et al (1990) Familial 5q11.2–q13.3 segmental duplication cosegregating with multiple anomalies including schizophrenia. American Journal of Medical Genetics, 35, 10–13.CrossRefGoogle ScholarPubMed
McKusick, V. A. (1990) Mendelian Inheritance in Man. Baltimore, MD: Johns Hopkins University Press.Google Scholar
Neville, J. (1959) Paranoid schizophrenia in a mongoloid defective: some theoretical considerations derived from an unusual case. Journal of Mental Science, 105, 444–447.Google Scholar
Nielsen, J., Astradur, B., Hreidarsson, B., et al (1973) D/D translocations in patients with mental illness. Hereditas, 75, 131–135.CrossRefGoogle ScholarPubMed
Oliver, C. & Holland, A. J. (1986) Down's syndrome and Alzheimer's disease: a review. Psychological Medicine, 16, 307–322.Google Scholar
Pinkel, D., Straume, T. & Gray, J. W. (1986) Cytogenetic analysis using quantitative, high sensitivity, fluorescence hybridization. Proceedings of the National Academy of Sciences, 83, 2934–2938.Google Scholar
Price, W. H., Brunton, M., Buckton, K., et al (1976) Chromosome survey of new patients admitted to the four maximum security hospitals in the United Kingdom. Clinical Genetics, 9, 389–398.Google Scholar
Propping, P. (1983) Genetic disorders presenting as ‘schizophrenia’: Karl Bonhoeffer's early view of the psychoses in the light of medical genetics. Human Genetics, 65, 1–10.Google Scholar
Ray, P. M., Belfall, B., Duff, C., et al (1985) Cloning of the breakpoint of an X;21 translocation associated with Duchenne muscular dystrophy. Nature, 318, 672–675.Google Scholar
Reid, A. H., Maloney, A. F. J. & Aungle, P. G. (1978) Dementia in ageing mental defectives: a clinical and neuropathological study. Journal of Mental Deficiency Research, 22, 233–241.Google Scholar
Risch, N. (1990) Linkage strategies for genetically complex traits: I. Multilocus traits. American Journal of Human Genetics, 46, 222–228.Google Scholar
Roberts, S. H., Cowie, V. A. & Singh, K. R. (1986) Intrachromosomal insertion of chromosome 13 in a family with psychosis and mental subnormality. Journal of Mental Deficiency Research, 30, 227–232.Google Scholar
Romain, D. R., Chapman, C. J., Columbano-Green, L., et al (1982) Two pericentric inversions, inv(2)(p11q13) and inv(5)(p13q13), in a patient referred for psychiatric problems. Journal of Medical Genetics, 19, 153–155.Google Scholar
Rudduck, C. & Franzén, G. (1983) A new heritable fragile site on human chromosome 3. Hereditas, 98, 297–299.CrossRefGoogle ScholarPubMed
Rudduck, C., Beckman, L., Franzén, G., et al (1985) C3 and C6 complement types in schizophrenia. Human Heredity, 35, 255–258.CrossRefGoogle ScholarPubMed
Schinzel, A. (1984) Catalogue of Unbalanced Chromosome Aberrations in Man. Berlin, New York: De Gruyter.Google Scholar
Schmid, W. & Nielsen, J. (eds) (1981) Human Behavior and Genetics. Amsterdam: Elsevier/North Holland Biomedical Press.Google Scholar
Sherrington, R., Brynjolfsson, J., Petursson, H., et al (1988) Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature, 339, 164–167.Google Scholar
Smith, M., Wasmuth, J., McPherson, J. D., et al (1989) Cosegregation of an 11q22.3–9p22 translocation with affective disorder: proximity of the dopamine D2 receptor gene relative to the translocation breakpoint. American Journal of Human Genetics, 45, A178.Google Scholar
Smith, M., Smalley, S., Cantor, R., et al (1990) Mapping of a gene determining tuberous sclerosis to human chromosome 11q14–11q23. Genomics, 6, 105–114.Google Scholar
Sperber, M. A. (1975) Schizophrenia and organic brain syndrome with trisomy 8 (group C trisomy 8 [47,XX,8+]). Biological Psychiatry, 10, 27–43.Google Scholar
St Clair, D. M., Blackwood, D., Muir, W., et al (1989) No linkage of chromosome 5q11–q13 markers to schizophrenia in Scottish families. Nature, 339, 305–309.Google Scholar
St Clair, D. M., Blackwood, D., Muir, W., et al (1990) Association within a family of a balanced autosomal translocation with major mental illness. Lancet, 336, 13–16.CrossRefGoogle ScholarPubMed
St George-Hyslop, P. H., Tanzi, R. E., Polinsky, R. J., et al (1987) The genetic defect causing familial Alzheimer's disease on chromosome 21. Science, 235, 885–890.Google Scholar
Tengström, C. & Autio, S. (1987) Chromosomal aberrations in 85 mentally retarded patients examined by high resolution banding. Clinical Genetics, 31, 53–60.Google Scholar
Theilgaard, A., Lundsteen, C., Parving, H.-H., et al (1977) Trisomy 8 syndrome: a psychological and somatic study of a mentally non-retarded male with 46, XY/47, XY, + 8 chromosome constitution. Clinical Genetics, 12, 227–232.Google Scholar
Tommerup, N., Nielsen, J. & Mikkelsen, M. (1985) A folate sensitive heritable fragile site at 19p13. Clinical Genetics, 27, 510–514.Google Scholar
Turner, T. H. (1989) Schizophrenia and mental handicap: an historical review, with implications for further research. Psychological Medicine, 19, 301–314.Google Scholar
Verkerk, A. J. M. H., Pieretti, M., Sutcliffe, J. S., et al (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, 65, 905–914.Google Scholar
Wallace, M. R., Marchuk, D. A., Andersen, L. B., et al (1990) Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science, 249, 181–186.Google Scholar
Yunis, J. & Ramsay, N. (1978) Retinoblastoma and subband deletion of chromosome 13. American Journal of Diseases of Children, 132, 161–163.Google Scholar
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