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Chromosome 11 in Schizophrenia and Bipolar Diseases

CITATION:  Klar, Amar J.S., (2004)  A Genetic Mechanism Implicates Chromosome 11 in Schizophrenia and Bipolar Diseases.  Genetics, Vol. 167, 1833-1840.

ABSTRACT:  The causes of schizophrenia and bipolar human psychiatric disorders are unknown. A novel somatic cell genetic model postulated nonrandom segregation of "Watson" vs. "Crick" DNA chains of both copies of a chromosome to specific daughter cells. Such an oriented asymmetric cell division causes development of healthy, functionally nonequivalent brain hemispheres. Genetic translocations of the chromosome may cause disease by disrupting the biased strand-segregation process. Only one-half of chromosome 1 and 11 translocation carriers developing disease were recently explained as a result consistent with the model (KLAR 2002). Is chromosome 1 or 11 involved? Does the translocation breakpoint cause disease? Remarkably, two other unrelated chromosome 11 translocations discovered from the literature likewise caused disease in  50% of carriers. Together, their breakpoints lie at three distinct regions spanning  40% of chromosome 11. Thus, chromosome 11 is implicated but the breakpoints themselves are unlikely to cause the disease. The results suggest that the genetically caused disease develops without a Mendelian gene mutation. 

References

Bassett, a. S., 1992 chromosomal aberrations and schizophrenia. Br. J. Psychiatry 161: 323–334.[abstract]

Baysal, b. E., s. G. Potkin, j. E. Farr, m. J. Higgins, j. Korcz et al., 1998 bipolar affective disorder partially cosegregates with a balanced t(9;11)(p24;q23.1) chromosomal translocation in a small pedigree. Am. J. Med. Genet. 81: 81–91.[crossref][medline]

Baysal, b. E., j. E. Willett-brozick, j. A. Badner, w. Corona, r. E. Ferrell et al., 2002 a mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint that co-segregates with bipolar affective disorder in a small family. Neurogenetics 4: 43–53.[crossref][medline]

Boklage, c. E., 1977 schizophrenia, brain asymmetry development, and twinning: cellular relationship with etiological and possible prognosis implications. Biol. Psychiatry 12: 19–35.[medline]

Cairns, j., 1975 mutation selection and the natural history of cancer. Nature 255: 197–200.[medline]

Craddock, n., and m. Owen, 1994 chromosomal aberrations and bipolar affective disorder. Br. J. Psychiatry 164: 507–512.[abstract]

Crow, t. J., 1990 the continuum of psychosis and its genetic origins. The sixty-fifth maudsley lecture. Br. J. Psychiatry 156: 788–797.[abstract]

Delisi, l. E., and m. Lovett, 1990 the role of molecular genetics in psychiatry: unravelling the etiology of schizophrenia, pp. 131–161 in recent advances in schizophrenia, edited by a. Kales, c. N. Stefanis and j. Talbort. Springer-verlag, new york.

Delisi, l. E., m. Sakuma, m. Kushner, d. L. Finer, a. L. Hoff et al., 1997 anomalous cerebral asymmetry and language processing in schizophrenia. Schizophr. Bull. 23: 255–271.[medline]

Devon, r. S., s. Anderson, p. W. Teague, p. Burgess, t. M. Kipari et al., 2001 identification of polymorphisms within disrupted in schizophrenia 1 and disrupted in schizophrenia 2, and an investigation of their association with schizophrenia and bipolar affective disorder. Psychiatr. Genet. 11: 71–78.[crossref][medline]

Evans, k. L., w. J. Muir, d. H. Blackwood and d. J. Porteous, 2001 nuts and bolts of psychiatric genetics: building on the human genome project. Trends genet. 17: 35–40.[crossref][medline]

Fisher, d., and m. Mechali, 2003 vertebrate hoxb gene expression requires dna replication. Embo j. 22: 3737–3748.[abstract/free full text]

Holland, t., and c. Gosden, 1990 a balanced chromosomal translocation partially co-segregating with psychotic illness in a family. Psychiatry res. 32: 1–8.[crossref][medline]

Hoshi, s., 1999 acute promyelocytic leukemia with t(11;17)(q23;q21). Rinsho ketsueki 40: 119–123.[medline] Jeffries, a. R., a. J. Mungall, e. Dawson, k. Halls, c. F. Langford et al., 2003 beta-1,3-glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation. Mol. Psychiatry 8: 654–663.[crossref][medline]

Kennedy, j. L., l. A. Farrer, n. C. Andreasen, r. Mayeux and p. St. George-hyslop, 2003 the genetics of adult-onset neuropsychiatric disease: complexities and conundra? Science 302: 822–826.[abstract/free full text]

Kitsberg, d., s. Selig, m. Brandeis, i. Simon, i. Keshet et al., 1993 allele-specific replication timing of imprinted gene regions. Nature 364: 459–463.[crossref][medline]

Klar, a. J., 1996 a single locus, rght, specifies preference for hand utilization in humans. Cold spring harbor symp. Quant. Biol. 61: 59–65.[medline]

Klar, a. J., 1999 genetic models for handedness, brain lateralization, schizophrenia, and manic-depression. Schizophr. Res. 39: 207–218.[crossref][medline]

Klar, a. J., 2002 the chromosome 1;11 translocation provides the best evidence supporting genetic etiology for schizophrenia and bipolar affective disorders. Genetics 160: 1745–1747.[abstract/free full text]

Klar, a. J., 2003 human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 165: 269–276.[abstract/free full text]

Klar, a. J. S., 2001 differentiated parental dna chain causes stem cell pattern of cell-type switching in schizosaccharomyces pombe, pp.15–35 in stem cell biology, edited by d. R. Marshak, r. L. Gardner and d. 
Gottlieb. Cold spring harbor laboratory press, cold spring harbor, ny.

Lasalle, j. M., and m. Lalande, 1996 homologous association of oppositely imprinted chromosomal domains. Science 272: 725–728.[abstract]

Ledgerwood, l. G., p. W. Ewald and g. M. Cochran, 2003 genes, germs, and schizophrenia: an evolutionary perspective. Perspect. Biol. Med. 46: 317–348.[medline]

Levinson, d. F., p. A. Holmans, c. Laurent, b. Riley, a. E. Pulver et al., 2002 no major schizophrenia locus detected on chromosome 1q in a large multicenter sample. Science 296: 739–741.[abstract/free full text]

Lewis, c. M., d. F. Levinson, l. H. Wise, l. E. Delisi, r. E. Straub et al., 2003 genome scan meta-analysis of schizophrenia and bipolar disorder. Ii. Schizophrenia. Am. J. Hum. Genet. 73: 34–48.[crossref][medline]

Liu, p., n. A. Jenkins and n. G. Copeland, 2002 efficient cre-loxp-induced mitotic recombination in mouse embryonic stem cells. Nat. Genet. 30: 66–72.[crossref][medline]

Merok, j. R., j. A. Lansita, j. R. Tunstead and j. L. Sherley, 2002 cosegregation of chromosomes containing immortal dna strands in cells that cycle with asymmetric stem cell kinetics. Cancer res. 62: 6791–6795.[abstract/free full text]

Millar, j. K., p. A. Thomson, n. R. Wray, w. J. Muir, d. H. Blackwood et al., 2003 response to amar j. Klar: the chromosome 1;11 translocation provides the best evidence supporting genetic etiology for schizophrenia and bipolar affective disorders. Genetics 163: 833–835.[free full text]

Riesselmann, l., and t. Haaf, 1999 preferential s-phase pairing of the imprinted region on distal mouse chromosome 7. Cytogenet. Cell genet. 86: 39–42.[medline]

Segurado, r., s. D. Detera-wadleigh, d. F. Levinson, c. M. Lewis, m. Gill et al., 2003 genome scan meta-analysis of schizophrenia and bipolar disorder. Iii. Bipolar disorder. Am. J. Hum. Genet. 73: 49–62.[crossref][medline]

Van den oord, e. J., p. F. Sullivan, y. Jiang, d. Walsh, f. A. O'neill et al., 2003 identification of a high-risk haplotype for the dystrobrevin binding protein 1 (dtnbp1) gene in the irish study of high-density schizophrenia families. Mol. Psychiatry 8: 499–510.[crossref][medline]

Watson, j. D., and f. H. Crick, 1953 molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171: 737–738.