Chromosomal abnormalities and mental illness

ABSTRACT Linkage studies of mental illness have provided suggestive evidence of susceptibility loci over many broad chromosomal regions. Pinpointing causative gene mutations by conventional

linkage strategies alone is problematic. The breakpoints of chromosomal abnormalities occurring in patients with mental illness may be more direct pointers to the relevant gene locus.

Publications that describe patients where chromosomal abnormalities co-exist with mental illness are reviewed along with supporting evidence that this may amount to an association.

Chromosomal abnormalities are considered to be of possible significance if (a) the abnormality is rare and there are independent reports of its coexistence with psychiatric illness, or (b)

there is colocalisation of the abnormality with a region of suggestive linkage findings, or (c) there is an apparent cosegregation of the abnormality with psychiatric illness within the

individual's family. Breakpoints have been described within many of the loci suggested by linkage studies and these findings support the hypothesis that shared susceptibility factors

for schizophrenia and bipolar disorder may exist. If these abnormalities directly disrupt coding regions, then combining molecular genetic breakpoint cloning with bioinformatic sequence

analysis may be a method of rapidly identifying candidate genes. Full karyotyping of individuals with psychotic illness especially where this coexists with mild learning disability,

dysmorphism or a strong family history of mental disorder is encouraged. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $259.00 per year only $21.58 per issue Learn more Buy this

article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in

* Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * McGuffin P, Owen MJ, Farmer AE . Genetic basis of schizophrenia. _Lancet_ 1995; 346:

678–682. Article  CAS  PubMed  Google Scholar  * Craddock N, McGuffin P . Approaches to the genetics of affective disorders. _Ann Med_ 1993; 25: 317–322. Article  CAS  PubMed  Google Scholar

  * Evans KL, Muir WJ, Blackwood DH, Porteous DJ . Nuts and bolts of psychiatric genetics: building on the Human Genome Project. _Trends Genet_ 2001; 17: 35–40. Article  CAS  PubMed  Google

Scholar  * APA. _Diagnostic and Statistical Manual of Mental Disorders_. American Psychiatric Association: Washington, DC. * WHO. _The ICD-10 Classification of Mental and Behavioural

Disorders. Clinical Descriptions and Diagnostic guidelines_. World Health Organisation: Geneva. * Berrettini WH . Are schizophrenic and bipolar disorders related? A review of family and

molecular studies. _Biol Psychiatry_ 2000; 48: 531–538. CAS  PubMed  Google Scholar  * Wildenauer DB, Schwab SG, Maier W, Detera-Wadleigh SD . Do schizophrenia and affective disorder share

susceptibility genes? _Schizophr Res_ 1999; 39: 107–111. Article  CAS  PubMed  Google Scholar  * Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ . Major depression and generalized

anxiety disorder. Same genes, partly different environments? _Arch Gen Psychiatry_ 1992; 49: 716–722. Article  CAS  PubMed  Google Scholar  * McGue M, Gottesman, II . A single dominant gene

still cannot account for the transmission of schizophrenia. _Arch Gen Psychiatry_ 1989; 46: 478–480. Article  CAS  PubMed  Google Scholar  * Sherrington R, Brynjolfsson J, Petursson H,

Potter M, Dudleston K, Barraclough B et al. Localization of a susceptibility locus for schizophrenia on chromosome 5. _Nature_ 1988; 336: 164–167. Article  CAS  PubMed  Google Scholar  * St

Clair D, Blackwood D, Muir W, Baillie D, Hubbard A, Wright A et al. No linkage of chromosome 5q11–q13 markers to schizophrenia in Scottish families. _Nature_ 1989; 339: 305–309. Article  CAS

  PubMed  Google Scholar  * Riley BP, McGuffin P . Linkage and associated studies of schizophrenia. _Am J Med Genet_ 2000; 97: 23–44. Article  CAS  PubMed  Google Scholar  * Potash JB,

DePaulo Jr JR . Searching high and low: a review of the genetics of bipolar disorder. _Bipolar Disorders_ 2000; 2: 8–26. Article  CAS  PubMed  Google Scholar  * Berrettini WH .

Susceptibility loci for bipolar disorder: overlap with inherited vulnerability to schizophrenia. _Biol Psychiatry_ 2000; 47: 245–251. Article  CAS  PubMed  Google Scholar  * Blackwood DH,

Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ . Schizophrenia and affective disorders—cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed

genes: clinical and P300 findings in a family. _Am J Hum Genet_ 2001; 69: 428–433. Article  CAS  PubMed  PubMed Central  Google Scholar  * Collins FS . Positional cloning: let's not

call it reverse anymore. _Nat Genet_ 1992; 1: 3–6. Article  CAS  PubMed  Google Scholar  * Collins FS . Positional cloning moves from perditional to traditional. _Nat Genet_ 1995; 9:

347–350. Article  CAS  PubMed  Google Scholar  * Gostason R, Wahlstrom J, Johannisson T, Holmqvist D . Chromosomal aberrations in the mildly mentally retarded. _J Ment Defic Res_ 1991; 35:

240–246. PubMed  Google Scholar  * Doody GA, Johnstone EC, Sanderson TL, Owens DG, Muir WJ . ‘Pfropfschizophrenie’ revisited. Schizophrenia in people with mild learning disability. _Br J

Psychiatry_ 1998; 173: 145–153. Article  CAS  PubMed  Google Scholar  * Sanderson TL, Doody GA, Best J, Owens DG, Johnstone EC . Correlations between clinical and historical variables and

cerebral structural variables, in people with mild intellectual disability and schizophrenia. _J Intellect Disabil Res_ 2001; 45: 89–98. Article  CAS  PubMed  Google Scholar  * St Clair D,

Blackwood D, Muir W, Carothers A, Walker M, Spowart G et al. Association within a family of a balanced autosomal translocation with major mental illness. _Lancet_ 1990; 336: 13–16. Article 

CAS  PubMed  Google Scholar  * Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA et al. Disruption of two novel genes by a translocation co-segregating with

schizophrenia. _Hum Mol Genet_ 2000; 9: 1415–1423. Article  CAS  PubMed  Google Scholar  * Ekelund J, Hovatta I, Parker A, Paunio T, Varilo T, Martin R et al. Chromosome 1 loci in Finnish

schizophrenia families. _Hum Mol Genet_ 2001; 10: 1611–1617. Article  CAS  PubMed  Google Scholar  * Gratacos M, Nadal M, Martin-Santos R, Pujana MA, Gago J, Peral B et al. A polymorphic

genomic duplication on human chromosome 15 is a susceptibility factor for panic and phobic disorders. _Cell_ 2001; 106: 367–379. Article  CAS  PubMed  Google Scholar  * Weissman MM, Bland

RC, Canino GJ, Faravelli C, Greenwald S, Hwu HG et al. The cross-national epidemiology of panic disorder. _Arch Gen Psychiatry_ 1997; 54: 305–309. Article  CAS  PubMed  Google Scholar  *

Bassett ASC, Chow EW, Weksberg R . Chromosomal abnormalities and schizophrenia. _Am J Med Genet_ 2000; 97: 45–51. Article  Google Scholar  * Craddock N, Owen M . Chromosomal aberrations and

bipolar affective disorder. _Br J Psychiatry_ 1994; 164: 507–512. Article  CAS  PubMed  Google Scholar  * DeLisi LE, Friedrich U, Wahlstrom J, Boccio-Smith A, Forsman A, Eklund K et al.

Schizophrenia and sex chromosome anomalies. _Schizophr Bull_ 1994; 20: 495–505. Article  CAS  PubMed  Google Scholar  * Ekelund J, Lichtermann D, Hovatta I, Ellonen P, Suvisaari J,

Terwilliger JD et al. Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22. _Hum Mol Genet_ 2000; 9: 1049–1057. Article  CAS  PubMed  Google

Scholar  * Hovatta I, Varilo T, Suvisaari J, Terwilliger JD, Ollikainen V, Arajarvi R et al. A genomewide screen for schizophrenia genes in an isolated Finnish subpopulation,suggesting

multiple susceptibility loci. _Am J Hum Genet_ 1999; 65: 1114–1124. Article  CAS  PubMed  PubMed Central  Google Scholar  * Detera-Wadleigh SD, Badner JA, Berrettini WH, Yoshikawa T, Goldin

LR, Turner G et al. A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2. _Proc Natl Acad Sci USA_

1999; 96: 5604–5609. Article  CAS  PubMed  PubMed Central  Google Scholar  * Bassett AS, McGillivray BC, Jones BD, Pantzar JT . Partial trisomy chromosome 5 cosegregating with schizophrenia.

_Lancet_ 1988; 1: 799–801. Article  CAS  PubMed  PubMed Central  Google Scholar  * Aschauer HN, Aschauer-Treiber G, Isenberg KE, Todd RD, Knesevich MA, Garver DL et al. No evidence for

linkage between chromosome 5 markers and schizophrenia. _Hum Hered_ 1990; 40: 109–115. Article  CAS  PubMed  Google Scholar  * Bennett RL, Karayiorgou M, Sobin CA, Norwood TH, Kay MA .

Identification of an interstitial deletion in an adult female with schizophrenia, mental retardation, and dysmorphic features: further support for a putative schizophrenia-susceptibility

locus at 5q21–23.1. _Am J Hum Genet_ 1997; 61: 1450–1454. Article  CAS  PubMed  PubMed Central  Google Scholar  * Schwab SG, Eckstein GN, Hallmayer J, Lerer B, Albus M, Borrmann M et al.

Evidence suggestive of a locus on chromosome 5q31 contributing to susceptibility for schizophrenia in German and Israeli families by multipoint affected sib-pair linkage analysis. _Mol

Psychiatry_ 1997; 2: 156–160. Article  CAS  PubMed  Google Scholar  * Straub RE, MacLean CJ, O'Neill FA, Walsh D, Kendler KS . Support for a possible schizophrenia vulnerability locus

in region 5q22–31 in Irish families. _Mol Psychiatry_ 1997; 2: 148–155. Article  CAS  PubMed  Google Scholar  * Gordon CT, Krasnewich D, White B, Lenane M, Rapoport JL . Brief report:

translocation involving chromosomes 1 and 7 in a boy with childhood-onset schizophrenia. _J Autism Dev Disor_ 1994; 24: 537–545. Article  CAS  Google Scholar  * Blouin JL, Dombroski BA, Nath

SK, Lasseter VK, Wolyniec PS, Nestadt G et al. Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21. _Nat Genet_ 1998; 20: 70–73. Article  CAS  PubMed  Google Scholar  * Faraone

SV, Matise T, Svrakic D, Pepple J, Malaspina D, Suarez B et al. Genome scan of European–American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium.

_Am J Med Genet_ 1998; 81: 290–295. Article  CAS  PubMed  Google Scholar  * Axelsson R, Wahlstrom J . Mental disorder and inversion on chromosome 9. _Hereditas_ 1981; 95: 337. Article  CAS 

PubMed  Google Scholar  * Axelsson R, Wahlstrom J . Chromosome aberrations in patients with paranoid psychosis. _Hereditas_ 1984; 100: 29–31. Article  CAS  PubMed  Google Scholar  * Kunugi

H, Lee KB, Nanko S . Cytogenetic findings in 250 schizophrenics: evidence confirming an excess of the X chromosome aneuploidies and pericentric inversion of chromosome 9. _Schizophr Res_

1999; 40: 43–47. Article  CAS  PubMed  Google Scholar  * Nanko S . Schizophrenia with pericentric inversion of chromosome 9: a case report. _Jap J Psychiatr Neurol_ 1993; 47: 47–49. CAS 

Google Scholar  * Toyota T, Shimizu H, Yamada K, Yoshitsugu K, Meerabux J, Hattori E et al. Karyotype analysis of 161 unrelated schizophrenics: no increased rates of X chromosome mosaicism

or inv(9), using ethnically matched and age-stratified controls. _Schizophr Res_ 2001; 52: 171–179. Article  CAS  PubMed  Google Scholar  * Smith M, Wasmuth JJ, McPherson JD . Cosegregation

of an 11q22.3–9p22 translocation with affective disorder: proximity of the dopamine D2 receptor gene relative to the translocation breakpoint. _Am J Hum Genet_ 1989; 45: A178. * Baysal BE,

Potkin SG, Farr JE, Higgins MJ, Korcz J, Gollin SM et al. Bipolar affective disorder partially cosegregates with a balanced t(9;11)(p24;q23.1) chromosomal translocation in a small pedigree.

_Am J Med Genet_ 1998; 81: 81–91. Article  CAS  PubMed  Google Scholar  * Inayama Y, Yoneda H, Fukushima K, Sakai J, Asaba H, Sakai T . Paracentric inversion of chromosome 9 with

schizoaffective disorder. _Clin Genet_ 1997; 51: 69–70. Article  CAS  PubMed  Google Scholar  * Park JP, Moeschler JB, Berg SZ, Wurster-Hill DH . Schizophrenia and mental retardation in an

adult male with a _de novo_ interstitial deletion 9(q32q34.1). _J Med Genet_ 1991; 28: 282–283. Article  CAS  PubMed  PubMed Central  Google Scholar  * Kaufmann CA, Suarez B, Malaspina D,

Pepple J, Svrakic D, Markel PD et al. NIMH Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees. _Am J Med Genet_ 1998; 81: 282–289. Article

  CAS  PubMed  Google Scholar  * Riley BP, Tahir E, Rajagopalan S, Mogudi-Carter M, Faure S, Weissenbach J et al. A linkage study of the N-methyl-D-aspartate receptor subunit gene loci and

schizophrenia in southern African Bantu-speaking families. _Psychiatr Genet_ 1997; 7: 57–74. Article  CAS  PubMed  Google Scholar  * Schwab SG, Hallmayer J, Albus M, Lerer B, Hanses C,

Kanyas K et al. Further evidence for a susceptibility locus on chromosome 10p14–p11 in 72 families with schizophrenia by nonparametric linkage analysis. _Am J Med Genet_ 1998; 81: 302–307.

Article  CAS  PubMed  Google Scholar  * Straub RE, MacLean CJ, Martin RB, Ma Y, Myakishev MV, Harris-Kerr C et al. A schizophrenia locus may be located in region 10p15–p11. _Am J Med Genet_

1998; 81: 296–301. Article  CAS  PubMed  Google Scholar  * Foroud T, Castelluccio PF, Koller DL, Edenberg HJ, Miller M, Bowman E et al. Suggestive evidence of a locus on chromosome 10p using

the NIMH genetics initiative bipolar affective disorder pedigrees. _Am J Med Genet_ 2000; 96: 18–23. Article  CAS  PubMed  Google Scholar  * Daw SC, Taylor C, Kraman M, Call K, Mao J,

Schuffenhauer S et al. A common region of 10p deleted in DiGeorge and velocardiofacial syndromes. _Nat Genet_ 1996; 13: 458–460. Article  CAS  PubMed  Google Scholar  * Lipson A, Fagan K,

Colley A, Colley P, Sholler G, Issacs D et al. Velo-cardio-facial and partial DiGeorge phenotype in a child with interstitial deletion at 10p13—implications for cytogenetics and molecular

biology. _Am J Med Genet_ 1996; 65: 304–308. Article  CAS  PubMed  Google Scholar  * Roberts SH, Cowie VA, Singh KR . Intrachromosomal insertion of chromosome 13 in a family with psychosis

and mental subnormality. _J Ment Defic Res_ 1986; 30: 227–232. PubMed  Google Scholar  * Calzolari E, Aiello V, Palazzi P, Sensi A, Calzolari S, Orrico D et al. Psychiatric disorder in a

familial 15;18 translocation and sublocalization of myelin basic protein of 18q22.3. _Am J Med Gene_ 1996; 67: 154–161. Article  CAS  Google Scholar  * Freedman R, Leonard S, Gault JM,

Hopkins J, Cloninger CR, Kaufmann CA et al. Linkage disequilibrium for schizophrenia at the chromosome 15q13–14 locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7).

_Am J Med Genet_ 2001; 105: 20–22. Article  CAS  PubMed  Google Scholar  * Leonard S, Gault J, Moore T, Hopkins J, Robinson M, Olincy A et al. Further investigation of a chromosome 15 locus

in schizophrenia: analysis of affected sibpairs from the NIMH Genetics Initiative. _Am J Med Genet_ 1998; 81: 308–312. Article  CAS  PubMed  Google Scholar  * Riley BP, Makoff A,

Mogudi-Carter M, Jenkins T, Williamson R, Collier D et al. Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene region to schizophrenia in Southern African Bantu

families. _Am J Med Genet_ 2000; 96: 196–201. Article  CAS  PubMed  Google Scholar  * Curtis L, Blouin JL, Radhakrishna U, Gehrig C, Lasseter VK, Wolyniec P et al. No evidence for linkage

between schizophrenia and markers at chromosome 15q13–14. _Am J Med Genet_ 1999; 88: 109–112. Article  CAS  PubMed  Google Scholar  * Neves-Pereira M, Bassett AS, Honer WG, Lang D, King NA,

Kennedy JL . No evidence for linkage of the CHRNA7 gene region in Canadian schizophrenia families. _Am J Med Genet_ 1998; 81: 361–363. Article  CAS  PubMed  PubMed Central  Google Scholar  *

Boer H, Holland A, Whittington J, Butler J, Webb T, Clarke D . Psychotic illness in people with Prader–Willi syndrome due to chromosome 15 maternal uniparental disomy. _Lancet_ 2002; 359:

135–136. Article  PubMed  Google Scholar  * Mors O, Ewald H, Blackwood D, Muir W . Cytogenetic abnormalities on chromosome 18 associated with bipolar affective disorder or schizophrenia. _Br

J Psychiatry_ 1997; 170: 278–280. Article  CAS  PubMed  Google Scholar  * Berrettini WH, Ferraro TN, Goldin LR, Detera-Wadleigh SD, Choi H, Muniec D et al. A linkage study of bipolar

illness. _Arch Gen Psychiatry_ 1997; 54: 27–35. Article  CAS  PubMed  Google Scholar  * Schwab SG, Hallmayer J, Lerer B, Albus M, Borrmann M, Honig S et al. Support for a chromosome 18p

locus conferring susceptibility to functional psychoses in families with schizophrenia, by association and linkage analysis. _Am J Hum Genet_ 1998; 63: 1139–1152. Article  CAS  PubMed 

PubMed Central  Google Scholar  * Overhauser J, Berrettini WH, Rojas K . Affective disorder associated with a balanced translocation involving chromosome 14 and 18. _Psychiatry Genet_ 1998;

8: 53–56. Article  CAS  Google Scholar  * Maziade M, Roy MA, Rouillard E, Bissonnette L, Fournier JP, Roy A et al. A search for specific and common susceptibility loci for schizophrenia and

bipolar disorder: a linkage study in 13 target chromosomes. _Mol Psychiatry_ 2001; 6: 684–693. Article  CAS  PubMed  Google Scholar  * McMahon FJ, Hopkins PJ, Xu J, McInnis MG, Shaw S,

Cardon L et al. Linkage of bipolar affective disorder to chromosome 18 markers in a new pedigree series. _Am J Hum Genet_ 1997; 61: 1397–1404. Article  CAS  PubMed  PubMed Central  Google

Scholar  * Stine OC, Xu J, Koskela R, McMahon FJ, Gschwend M, Friddle C et al. Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect. _Am J Hum Genet_

1995; 57: 1384–1394. CAS  PubMed  PubMed Central  Google Scholar  * Collacott RA, Cooper SA, McGrother C . Differential rates of psychiatric disorders in adults with Down's syndrome

compared with other mentally handicapped adults. _Br J Psychiatry_ 1992; 161: 671–674. Article  CAS  PubMed  Google Scholar  * el-Badramany MH, Farag TI, al-Awadi SA, Hammad IM, Abdelkader

A, Murthy DS . Familial manic-depressive illness with deleted short arm of chromosome 21: coincidental or causal? _Br J Psychiatry_ 1989; 155: 856–857. Article  CAS  PubMed  Google Scholar 

* Aita VM, Liu J, Knowles JA, Terwilliger JD, Baltazar R, Grunn A et al. A comprehensive linkage analysis of chromosome 21q22 supports prior evidence for a putative bipolar affective

disorder locus. _Am J Hum Genet_ 1999; 64: 210–217. Article  CAS  PubMed  PubMed Central  Google Scholar  * Detera-Wadleigh SD, Badner JA, Goldin LR, Berrettini WH, Sanders AR, Rollins DY et

al. Affected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q. _Am J Hum Genet_ 1996; 58: 1279–1285. CAS  PubMed  PubMed Central 

Google Scholar  * Kwok JB, Adams LJ, Salmon JA, Donald JA, Mitchell PB, Schofield PR . Nonparametric simulation-based statistical analyses for bipolar affective disorder locus on chromosome

21q22.3. _Am J Med Genet_ 1999; 88: 99–102. Article  CAS  PubMed  Google Scholar  * Straub RE, Lehner T, Luo Y, Loth JE, Shao W, Sharpe L et al. A possible vulnerability locus for bipolar

affective disorder on chromosome 21q22.3. _Nat Genet_ 1994; 8: 291–296. Article  CAS  PubMed  Google Scholar  * Shprintzen RJ, Goldberg R, Golding-Kushner KJ, Marion RW . Late-onset

psychosis in the velo-cardio-facial syndrome. _Am J Med Genet_ 1992; 42: 141–142. Article  CAS  PubMed  Google Scholar  * Murphy KC, Jones LA, Owen MJ . High rates of schizophrenia in adults

with velo-cardio-facial syndrome. _Arch Gen Psychiatry_ 1999; 56: 940–945. Article  CAS  PubMed  Google Scholar  * Papolos DF, Faedda GL, Veit S, Goldberg R, Morrow B, Kucherlapati R et al.

Bipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder? _Am J Psychiatry_

1996; 153: 1541–1547. Article  CAS  PubMed  Google Scholar  * Pulver AE, Nestadt G, Goldberg R, Shprintzen RJ, Lamacz M, Wolyniec PS et al. Psychotic illness in patients diagnosed with

velo-cardio-facial syndrome and their relatives. _J Nerv Mental Dis_ 1994; 182: 476–478. Article  CAS  Google Scholar  * Karayiorgou M, Morris MA, Morrow B, Shprintzen RJ, Goldberg R, Borrow

J et al. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. _Proc Natl Acad Sci USA_ 1995; 92: 7612–7616. Article  CAS  PubMed  PubMed Central  Google

Scholar  * Shaw SH, Kelly M, Smith AB, Shields G, Hopkins PJ, Loftus J et al. A genome-wide search for schizophrenia susceptibility genes. _Am J Med Genet_ 1998; 81: 364–376. Article  CAS 

PubMed  Google Scholar  * Garver DL, Holcomb J, Mapua FM, Wilson R, Barnes B . Schizophrenia spectrum disorders: an autosomal-wide scan in multiplex pedigrees. _Schizophr Res_ 2001; 52:

145–160. Article  CAS  PubMed  Google Scholar  * Edenberg HJ, Foroud T, Conneally PM, Sorbel JJ, Carr K, Crose C et al. Initial genomic scan of the NIMH genetics initiative bipolar

pedigrees: chromosomes 3, 5, 15, 16, 17 and 22. _Am J Med Genet_ 1997; 74: 238–246. Article  CAS  PubMed  Google Scholar  * Kelsoe JR, Spence MA, Loetscher E, Foguet M, Sadovnick AD, Remick

RA et al. A genome survey indicates a possible susceptibility locus for bipolar disorder on chromosome 22. _Proc Natl Acad Sci USA_ 2001; 98: 585–590. Article  CAS  PubMed  PubMed Central 

Google Scholar  * Mors O, Mortensen PB, Ewald H . No evidence of increased risk for schizophrenia or bipolar affective disorder in persons with aneuploidies of the sex chromosomes.

_Psycholog Med_ 2001; 31: 425–430. Article  CAS  Google Scholar  * Eshkevari HS . Translocation of chromosome Xq24 to chromosome 12q15[46, X, t(X;12)(q24;q15)] its association with bipolar

affective disorder and mental retardation; first report of a new chromosomal abnormality. _Am J Med Genet_ 1997; 74: 607 (Abst). * Lucotte G, Landoulsi A, Berriche S, David F, Babron MC .

Manic depressive illness is linked to factor IX in a French pedigree. _Ann Genet_ 1992; 35: 93–95. CAS  PubMed  Google Scholar  * Pekkarinen P, Terwilliger J, Bredbacka PE, Lonnqvist J,

Peltonen L . Evidence of a predisposing locus to bipolar disorder on Xq24–q27.1 in an extended Finnish pedigree. _Genome Res_ 1995; 5: 105–115. Article  CAS  PubMed  Google Scholar  *

Sutherland GR, Baker E . The clinical significance of fragile sites on human chromosomes. _Clin Genet_ 2000; 58: 157–161. Article  CAS  PubMed  Google Scholar  * Caspersson T, Farber S,

Foley GE, Kudynowski J, Modest EJ, Simonsson E et al. Chemical differentiation along metaphase chromosomes. _Exp Cell Res_ 1968; 49: 219–222. Article  CAS  PubMed  Google Scholar  * Lander

ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J et al. Initial sequencing and analysis of the human genome. _Nature_ 2001; 409: 860–921. Article  CAS  PubMed  Google Scholar  * Daly

MJ, Rioux JD, Schaffner SF, Hudson TJ, Lander ES . High-resolution haplotype structure in the human genome. _Nat Genet_ 2001; 29: 229–232. Article  CAS  PubMed  Google Scholar  * Cheung VG,

Nowak N, Jang W, Kirsch IR, Zhao S, Chen XN et al. Integration of cytogenetic landmarks into the draft sequence of the human genome. _Nature_ 2001; 409: 953–958. Article  CAS  PubMed  PubMed

Central  Google Scholar  * Rioux JD, Daly MJ, Silverberg MS, Lindblad K, Steinhart H, Cohen Z et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn

disease. _Nat Genet_ 2001; 29: 223–228. Article  CAS  PubMed  Google Scholar  * Migaud M, Charlesworth P, Dempster M, Webster LC, Watabe AM, Makhinson M et al. Enhanced long-term

potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. _Nature_ 1998; 396: 433–439. Article  CAS  PubMed  Google Scholar  * Fananas L, Fuster C, Guillamat R,

Miro R . Chromosomal fragile site 1q21 in schizophrenic patients. _Am J Psychiatry_ 1997; 154: 716. CAS  PubMed  Google Scholar  * Turecki G, Smith M, Mari JJ . Type I bipolar disorder

associated with a fragile site on chromosome 1. _Am J Med Genet_ 1995; 60: 179–182. Article  CAS  PubMed  Google Scholar  * Maziade M, Debraekeleer M, Genest P, Cliche D, Fournier JP,

Garneau Y et al. A balanced 2:18 translocation and familial schizophrenia: falling short of an association. _Arch Gen Psychiatry_ 1993; 50: 73–75. CAS  PubMed  Google Scholar  * Glass IA,

Stormer P, Oei PT, Hacking E, Cotter PD . Trisomy 2q11.2→q21.1 resulting from an unbalanced insertion in two generations. _J Med Genet_ 1998; 35: 319–322. Article  CAS  PubMed  PubMed

Central  Google Scholar  * Rudduck C, Franzen G . A new heritable fragile site on human chromosome 3. _Hereditas_ 1983; 98: 297–299. Article  CAS  PubMed  Google Scholar  * Palmour RM,

Miller S, Fielding A, Vekemans M, Ervin FR . A contribution to the differential diagnosis of the ‘group of schizophrenias’: structural abnormality of chromosome 4. _J Psychiatry Neurosci_

1994; 19: 270–277. CAS  PubMed  PubMed Central  Google Scholar  * Malaspina D, Warburton D, Amador X, Harris M, Kaufmann CA . Association of schizophrenia and partial trisomy of chromosome

5p.A case report. _Schizophr Res_ 1992; 7: 191–196. Article  CAS  PubMed  Google Scholar  * Holland T, Gosden C . A balanced chromosomal translocation partially co-segregating with psychotic

illness in a family. _Psychiatr Res_ 1990; 32: 1–8. Article  CAS  Google Scholar  * Price WH, Brunton M, Buckton K, Jacobs PA . Chromosome survey of new patients admitted to the four

maximum security hospitals in the United Kingdom. _Clin Genet_ 1976; 9: 389–398. Article  CAS  PubMed  Google Scholar  * Sperber MA . Schizophrenia and organic brain syndrome with trisomy 8

(group-C trisomy 8 [47, XX, 8+]). _Biol Psychiatry_ 1975; 10: 27–43. CAS  PubMed  Google Scholar  * Garofalo G, Ragusa RM, Argiolas A, Scavuzzo C, Spina E, Barletta C . Evidence of

chromosomal fragile sites in schizophrenic patients. _Ann Genetique_ 1993; 36: 132–135. CAS  Google Scholar  * Escobar JI . A cytogenetic study of children with psychiatric disorders.

_Comprehensive Psychiatry_ 1976; 17: 309–313. Article  CAS  PubMed  Google Scholar  * Nielsen J, Hreidarsson AB, Christensen KR . D–D translocations in patients with mental illness.

_Hereditas_ 1973; 75: 131–135. Article  CAS  PubMed  Google Scholar  * Clarke DJ . Prader–Willi syndrome and psychoses. _Br J Psychiatry_ 1993; 163: 680–684. Article  CAS  PubMed  Google

Scholar  * Kerbeshian J, Burd L, Randall T, Martsolf J, Jalal S . Autism, profound mental retardation and atypical bipolar disorder in a 33-year-old female with a deletion of 15q12. _J Ment

Defic Res_ 1990; 34: 205–210. PubMed  Google Scholar  * Kerbeshian J, Severud R, Burd L, Larson L . Peek-a-boo fragile site at 16d associated with Tourette syndrome, bipolar disorder,

autistic disorder and mental retardation. _Am J Med Genet_ 2000; 96: 69–73. Article  CAS  PubMed  Google Scholar  * Christensen KR, Friedrich U, Jacobsen P, Jensen K, Nielsen J, Tsuboi T .

Ring chromosome 18 in mother and daughter. _J Ment Defic Res_ 1970; 14: 49–67. CAS  PubMed  Google Scholar  * Smith AB, Peterson P, Wieland J, Moriarty T, DeLisi LE . Chromosome 18

translocation (18;21) (p11.1;p11.1) associated with psychosis in one family. _Am J Med Genet_ 1996; 67: 560–563. Article  CAS  PubMed  Google Scholar  * Chodirker BN, Chudley AE, Ray M,

Wickstrom DE, Riordan DL . Fragile 19p13 in a family with mental illness. _Clin Genet_ 1987; 31: 1–6. Article  CAS  PubMed  Google Scholar  * Cooper SA, Collacott RA . Mania and Down's

syndrome. _Br J Psychiatry_ 1993; 162: 739–743. Article  CAS  PubMed  Google Scholar  * Craddock N, Owen M . Is there an inverse relationship between Down's syndrome and bipolar

affective disorder? Literature review and genetic implications. _J Intellect Disabil Res_ 1994; 38: 613–620. Article  PubMed  Google Scholar  * Myers BA, Pueschel SM . Major depression in a

small group of adults with Down syndrome. _Res Dev Disabil_ 1995; 16: 285–299. Article  CAS  PubMed  Google Scholar  * Panzer MJ, Tandon R . Bipolar disorder associated with Turner's

syndrome. _J Nerv Ment Dis_ 1991; 179: 702. Article  CAS  PubMed  Google Scholar  * Woodhouse WJ, Holland AJ, McLean G, Reveley AM . The association between triple X and psychosis. _Br J

Psychiatry_ 1992; 160: 554–557. Article  CAS  PubMed  Google Scholar  * Kawanishi C, Kono M, Onishi H, Ishii N, Ishii K . A case of Turner syndrome with schizophrenia: genetic relationship

between Turner syndrome and psychosis. _Psychiatry Clin Neurosci_ 1997; 51: 83–85. Article  CAS  PubMed  Google Scholar  * Prior TI, Chue PS, Tibbo P . Investigation of Turner syndrome in

schizophrenia. _Am J Med Genet_ 2000; 96: 373–378. Article  CAS  PubMed  Google Scholar  * Nanko S . Schizophrenia-like psychosis in a 46,XX male. _Folia Psychiatr Neurol Jpn_ 1981; 35:

461–463. Article  CAS  Google Scholar  * Rajagopalan M, MacBeth R, Varma SL . XYY chromosome anomaly and schizophrenia. _Am J Med Genet_ 1998; 81: 64–65. Article  CAS  PubMed  Google Scholar

  * Deckert J, Strik WK, Fritze J . Organic schizophrenic syndrome associated with symmetrical basal ganglia sclerosis and XO/XY-mosaic. _Biol Psychiatry_ 1992; 31: 401–403. Article  CAS 

PubMed  Google Scholar  * Baysal BE, Willett-Brozick JE, Badner JA, Corona W, Ferrell RE, Nimgaonkar VL et al. A mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint

that co-segregates with bipolar affective disorder in a small family. _Neurogenetics_ 2002; 4: 43–53. Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS DJ MacIntyre

was a research registrar supported by the Wellcome Trust. WJ Muir, D Blackwood and DJ Porteous were in support of grant funding from the Scottish Executive, the Medical Research council. The

authors would also like to thank Dr Judy Fantes, MRC Human Genetics Unit, Edinburgh for her helpful comments on the manuscript. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of

Psychiatry, University of Edinburgh, Edinburgh, Scotland, UK D J MacIntyre, D H R Blackwood, B S Pickard & W J Muir * Department of Medical Sciences, University of Edinburgh, Edinburgh,

Scotland, UK D H R Blackwood, D J Porteous, B S Pickard & W J Muir Authors * D J MacIntyre View author publications You can also search for this author inPubMed Google Scholar * D H R

Blackwood View author publications You can also search for this author inPubMed Google Scholar * D J Porteous View author publications You can also search for this author inPubMed Google

Scholar * B S Pickard View author publications You can also search for this author inPubMed Google Scholar * W J Muir View author publications You can also search for this author inPubMed 

Google Scholar CORRESPONDING AUTHOR Correspondence to W J Muir. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE MacIntyre, D., Blackwood, D., Porteous,

D. _et al._ Chromosomal abnormalities and mental illness. _Mol Psychiatry_ 8, 275–287 (2003). https://doi.org/10.1038/sj.mp.4001232 Download citation * Received: 06 May 2002 * Revised: 10

May 2002 * Accepted: 11 July 2002 * Published: 27 March 2003 * Issue Date: March 2003 * DOI: https://doi.org/10.1038/sj.mp.4001232 SHARE THIS ARTICLE Anyone you share the following link with

will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt

content-sharing initiative KEYWORDS * schizophrenia * bipolar disorder * chromosomes * linkage * mental retardation * learning disability