Excitement and confusion on chromosome 6q: The challenges of neuropsychiatric genetics in microcosm

Molecular Psychiatry

Volumn 10, Issue 12, 2005, Pages 1062-1073

  Kohn, Y ^a   Lerer, B ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

Author keywords

Bipolar disorder; Chromosome 6q; Linkage; Molecular genetics; Schizophrenia

Indexed keywords

AUTOSOMAL RECESSIVE INHERITANCE; BIPOLAR DISORDER; CHROMOSOME 6Q; CONFUSION; DISEASE COURSE; DISEASE PREDISPOSITION; EXCITEMENT; GENE; GENE LOCUS; GENE MAPPING; GENETIC LINKAGE; GENETIC VARIABILITY; GENETICS; GENOTYPE; HUMAN; MAJOR DEPRESSION; MICROCOSM; MICROSATELLITE MARKER; NEUROPSYCHIATRY; PARKINSONISM; PRIORITY JOURNAL; PROTEOMICS; PSYCHOSIS; REVIEW; SCHIZOAFFECTIVE PSYCHOSIS; SCHIZOPHRENIA; TRACE AMINE RECEPTOR GENE 4;

BIPOLAR DISORDER; CHROMOSOMES, HUMAN, PAIR 6; GENETIC PREDISPOSITION TO DISEASE; HUMANS; LINKAGE (GENETICS); MENTAL DISORDERS; SCHIZOPHRENIA;

EID: 32844458681     PISSN: 13594184     EISSN: 14765578     Source Type: Journal    
DOI: 10.1038/sj.mp.4001738     Document Type: Review

References (73)

1. Riley BP, McGuffin P. Linkage and associated studies of schizophrenia. Am J Med Genet 2000; 97: 23-44.
2. Berrettini WH. Molecular linkage studies of bipolar disorders. Bipolar Disord 2001; 3: 276-283.
3. Kohn Y, Lerer B. Genetics of schizophrenia - linkage findings: a review. Israel J Psychiatr Rel Sci 2002; 39: 240-251.
4. Mathews CA, Reus VI. Genetic linkage in bipolar disorder. CNS Spectr 2003; 8: 891-904.
5. Badner JA, Gershon ES. Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 2002; 7: 405-411.
6. Lewis CM, Levinson DF, Wise LH, DeLisi LE, Straub RE, Hovatta I et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Hum Genet 2003; 73: 34-48.
7. Segurado R, Detera-Wadleigh SD, Levinson DF, Lewis CM, Gill M, Nurnberger Jr JI et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder. Am J Hum Genet 2003; 73: 49-62.
8. Straub R, Jiang Y, MacLean C, Ma Y, Webb B, Myakishev M et al. Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse Dysbindin gene, is associated with schizophrenia. Am J Hum Genet 2002; 71: 337-348.
9. Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 2002; 71: 877-892.
10. Shifman S, Bronstein M, Sternfeld M, Pisante-Shalom A, Lev-Lehman E, Weizman A et al. A highly significant association between a COMT haplotype and schizophrenia. Am J Hum Genet 2002; 71: 1296-1302.
11. Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H et al. Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proc Natl Acad Sci USA 2002; 99: 13675-13680.
12. Hattori E, Liu C, Badner J, Bonner T, Christian S, Maheshwari M et al. Polymorphisms at the g72/g30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series. Am J Hum Genet 2003; 72: 1131-1140.
13. Chen Q, He G, Wang XY, Chen QY, Liu XM, Gu ZZ et al. Positive association between synapsin II and schizophrenia. Biol Psychiatry 2004; 56: 177-181.
14. Duan J, Martinez M, Sanders AR, Hou C, Saitou N, Kitano T et al. Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia. Am J Hum Genet 2004; 75: 624-638.
15. Mukai J, Liu H, Burt RA, Swor DE, Lai WS, Karayiorgou M et al. Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Nat Genet 2004; 36: 725-731.
16. Prasad S, Chowdari KV, Wood J, Bhatia T, Deshpande SN, Nimgaonkar VL et al. Association analysis of NOTCH 4 polymorphisms with schizophrenia among two independent family based samples. Am J Med Genet B Neuropsychiatr Genet 2004; 131: 6-9.
17. Pimm J, McQuillin A, Thirumalai S, Lawrence J, Quested D, Bass N et al. The epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia. Am J Hum Genet 2005; 76: 902-907.
18. Brzustowicz LM, Honer WG, Chow EW, Little D, Hogan J, Hodgkinson K et al. Linkage of familial schizophrenia to chromosome 13q32. Am J Hum Genet 1999; 65: 1096-1103.
19. Kendler KS. Schizophrenia genetics and dysbindin: a corner turned? Am J Psychiatry 2004; 161: 1533-1536.
20. Kakiuchi C, Iwamoto K, Ishiwata M, Bundo M, Kasahara T, Kusumi I et al. Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder. Nat Genet 2003; 35: 171-175.
21. Liu H, Heath SC, Sobin C, Roos JL, Galke BL, Blundell ML et al. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc Natl Acad Sci USA 2002; 99: 3717-3722.
22. Berrettini W. Evidence for shared susceptibility in bipolar disorder and schizophrenia. Am J Med Genet 2003; 123C: 59-64.
23. Shifman S, Bronstein M, Sternfeld M, Pisante A, Weizman A, Reznik I et al. COMT: a common susceptibility gene in bipolar disorder and schizophrenia. Am J Med Genet 2004; 128B: 61-64.
24. Cao Q, Martinez M, Zhang J, Sanders AR, Badner JA, Cravchik A et al. Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. Genomics 1997; 43: 1-8.
25. Martinez M, Goldin LR, Cao Q, Zhang J, Sanders AR, Nancarrow DJ et al. Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q. Am J Med Genet 1999; 88: 337-343.
26. 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.
27. Levinson DF, Holmans P, Straub RE, Owen MJ, Wildenauer DB, Gejman PV et al. Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III. Am J Hum Genet 2000; 67: 652-663.
28. Bailer U, Leisch F, Meszaros K, Lenzinger E, Willinger U, Strobl R et al. Genome scan for susceptibility loci for schizophrenia. Neuropsychobiology 2000; 42: 175-182.
29. Williams NM, Norton N, Williams H, Ekholm B, Hamshere ML, Lindblom Y et al. A systematic genomewide linkage study in 353 sib pairs with schizophrenia. Am J Hum Genet 2003; 73: 1355-1367.
30. Lindholm E, Ekholm B, Shaw S, Jalonen P, Johansson G, Pettersson U et al. A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees. Am J Hum Genet 2001; 69: 96-105.
31. Lerer B, Segman R, Hamdan A, Kanyas K, Karni O, Kohn Y et al. Genome scan of Arab Israeli families maps a schizophrenia susceptibility gene to chromosome 6q23 and supports a locus at chromosome 10q24. Mol Psychiatry 2003; 8: 488-498.
32. Levi A, Kohn Y, Kanyas K, Amann D, Pae CU, Hamdan A et al. Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval. Eur J Hum Genet 2005; 6: 6.
33. Ikeda M, Iwata N, Suzuki T, Kitajima T, Yamanouchi Y, Kinoshita Y et al. No association of haplotype-tagging SNPs in TRAR4 with schizophrenia in Japanese patients. Schizophr Res 2005; 19: 19.
34. Amann D, Avidan N, Kanyas K, Kohn Y, Hamdan A, Ben-Asher E. The trace amine receptor 4 gene is not associated with schizophrenia in a sample linked to chromosome 6q23. Mol Psychiatry, (in press).
35. Edgar PF, Douglas JE, Cooper GJ, Dean B, Kydd R, Faull RL. Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia. Mol Psychiatry 2000; 5: 85-90.
36. Sanders AR, Gejman PV. Major corrections are indicated for 'Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia'. Mol Psychiatry 2001; 6: 10-12.
37. Bennett P, Segurado R, Jones I, Bort S, McCandless F, Lambert D et al. The Wellcome trust UK-Irish bipolar affective disorder sibling-pair genome screen: first stage report. Mol Psychiatry 2002; 7: 189-200.
38. Ewald H, Flint T, Kruse TA, Mors O. A genome-wide scan shows significant linkage between bipolar disorder and chromosome 12q24.3 and suggestive linkage to chromosomes 1p22-21, 4p16, 6q14-22, 10q26 and 16p13.3. Mol Psychiatry 2002; 7: 734-744.
39. Bailer U, Leisch F, Meszaros K, Lenzinger E, Willinger U, Strobl R et al. Genome scan for susceptibility loci for schizophrenia and bipolar disorder. Biol Psychiatry 2002; 52: 40-52.
40. McInnis MG, Dick DM, Willour VL, Avramopoulos D, MacKinnon DF, Simpson SG et al. Genome-wide scan and conditional analysis in bipolar disorder: evidence for genomic interaction in the National Institute of Mental Health genetics initiative bipolar pedigrees. Biol Psychiatry 2003; 54: 1265-1273.
41. Rice JP, Goate A, Williams JT, Bierut L, Dorr D, Wu W et al. Initial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 1, 6, 8, 10, and 12. Am J Med Genet 1997; 74: 247-253.
42. Dick DM, Foroud T, Flury L, Bowman ES, Miller MJ, Rau NL et al. Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative. Am J Hum Genet 2003; 73: 107-114.
43. (erratum in Am J Hum Genet 2003; 73: 979).
44. Schulze TG, Buervenich S, Badner JA, Steele CJ, Detera-Wadleigh SD, Dick D et al. Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees. Biol Psychiatry 2004; 56: 18-23.
45. Pato CN, Pato MT, Kirby A, Petryshen TL, Medeiros H, Carvalho C et al. Genome-wide scan in Portuguese Island families implicates multiple loci in bipolar disorder: fine mapping adds support on chromosomes 6 and 11. Am J Med Genet B Neuropsychiatr Genet 2004; 127: 30-34.
46. Middleton FA, Pato MT, Gentile KL, Morley CP, Zhao X, Eisener AF et al. Genomewide linkage analysis of bipolar disorder by use of a high-density single-nucleotide-polymorphism (SNP) genotyping assay: a comparison with microsatellite marker assays and finding of significant linkage to chromosome 6q22. Am J Hum Genet 2004; 74: 886-897.
47. Park N, Juo SH, Cheng R, Liu J, Loth JE, Lilliston B et al. Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci for bipolar disorder and shared susceptibility with schizophrenia. Mol Psychiatry 2004; 9: 1091-1099.
48. Park N, Cheng R, Juo SH, Liu J, Loth JE, Endicott J et al. Absence of psychosis may influence linkage results for bipolar disorder. Mol Psychiatry 2005; 10: 235-237.
49. Venken T, Claes S, Sluijs S, Paterson AD, van Duijn C, Adolfsson R et al. Genomewide scan for affective disorder susceptibility loci in families of a northern Swedish isolated population. Am J Hum Genet 2005; 76: 237-248.
50. Abou Jamra R, Sircar I, Becker T, Freudenberg-Hua Y, Ohlraun S, Freudenberg J et al. A family-based and case-control association study of trace amine receptor genes on chromosome 6q23 in bipolar affective disorder. Mol Psychiatry 2005; 10: 618-620.
51. Cichon S, Schumacher J, Muller DJ, Hurter M, Windemuth C, Strauch K et al. A genome screen for genes predisposing to bipolar affective disorder detects a new susceptibility locus on 8q. Hum Mol Genet 2001; 10: 2933-2944.
52. Zubenko GS, Maher BS, Hughes III HB, Zubenko WN, Stiffler JS, Marazita ML. Genome-wide linkage survey for genetic loci that affect the risk of suicide attempts in families with recurrent, early-onset, major depression. Am J Med Genet B Neuropsychiatr Genet 2004; 129: 47-54.
53. Philippe A, Martinez M, Guilloud-Bataille M, Gillberg C, Rastam M, Sponheim E et al. Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study. Hum Mol Genet 1999; 8: 805-812.
54. Kenealy SJ, Babron MC, Bradford Y, Schnetz-Boutaud N, Haines JL, Rimmler JB et al. A second-generation genomic screen for multiple sclerosis. Am J Hum Genet 2004; 75: 1070-1078.
55. Li JL, Hayden MR, Almqvist EW, Brinkman RR, Durr A, Dode C et al. A genome scan for modifiers of age at onset in Huntington disease: the HD MAPS study. Am J Hum Genet 2003; 73: 682-687.
56. Petryshen TL, Kaplan BJ, Fu Liu M, de French NS, Tobias R, Hughes ML et al. Evidence for a susceptibility locus on chromosome 6q influencing phonological coding dyslexia. Am J Med Genet 2001; 105: 507-517.
57. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998; 392: 605-608.
58. Ferland RJ, Eyaid W, Collura RV, Tully LD, Hill RS, Al-Nouri D et al. Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Nat Genet 2004; 36: 1008-1013.
59. Dixon-Salazar T, Silhavy JL, Marsh SE, Louie CM, Scott LC, Gururaj A et al. Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria. Am J Hum Genet 2004; 75: 979-987.
60. Lander E, Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995; 11: 241-247.
61. McQueen MB, Devlin B, Faraone SV, Nimgaonkar VL, Sklar P, Smoller JW et al. Combined analysis from eleven linkage studies of bipolar disorder provides strong evidence of susceptibility loci on chromosomes 6q and 8q. Am J Hum Genet 2005 (Epub ahead of print).
62. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L et al. The DNA sequence and analysis of human chromosome 6. Nature 2003; 425: 805-811.
63. Angst J, Marneros A. Bipolarity from ancient to modern times: conception, birth and rebirth. J Affect Disord 2001; 67: 3-19.
64. Crow TJ. A continuum of psychosis, one human gene, and not much else - the case for homogeneity. Schizophr Res 1995; 17: 135-145.
65. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160: 636-645.
66. 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.
67. 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.
68. Cargill M, Daley GQ. Mining for SNPs: putting the common variants - common disease hypothesis to the test. Pharmacogenomics 2000; 1: 27-37.
69. Fanous AH, Kendler KS. Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework. Mol Psychiatry 2005; 10: 6-13.
70. Stewart DR, von Allmen D. The genetics of Hirschsprung disease. Gastroenterol Clin North Am 2003; 32: 819-837, vi.
71. Edery P, Lyonnet S, Mulligan LM, Pelet A, Dow E, Abel L et al. Mutations of the RET proto-oncogene in Hirschsprung's disease. Nature 1994; 367: 378-380.
72. Emison ES, McCallion AS, Kashuk CS, Bush RT, Grice E, Lin S et al. A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature 2005; 434: 857-863.
73. Liu PY, Zhang YY, Lu Y, Long JR, Shen H, Zhao LJ et al. A survey of haplotype variants at several disease candidate genes: the importance of rare variants for complex diseases. J Med Genet 2005; 42: 221-227.