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ProtocadherinX/Y, a Candidate Gene-Pair for Schizophrenia and Schizoaffective Disorder: A DHPLC Investigation of Gonomic Sequence

Giouzeli, Ms M and Williams, Dr NA and Lonie, Dr LJ and DeLisi, Prof LE and Crow, Prof TJ (2004) ProtocadherinX/Y, a Candidate Gene-Pair for Schizophrenia and Schizoaffective Disorder: A DHPLC Investigation of Gonomic Sequence. [Journal (Paginated)]

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Abstract

Protocadherin X and Protocadherin Y (PCDHX and PCDHY) are cell-surface adhesion molecules expressed predominantly in the brain. The PCDHX/Y gene-pair was generated by an X-Y translocation approximately 3 million years ago (MYA) that gave rise to the Homo sapiens-specific region of Xq21.3 and Yp11.2 homology. Genes within this region are expected to code for sexually dimorphic human characteristics, including, for example, cerebral asymmetry a dimension of variation that has been suggested is relevant to psychosis. We examined differences in patients with schizophrenic or schizoaffective psychosis in the genomic sequence of PCDHX and PCDHY in coding and adjacent intronic sequences using denaturing high performance liquid chromatography (DHPLC). Three coding variants were detected in PCDHX and two in PCDHY. However, neither the coding variants nor the intronic polymorphisms could be related to psychosis within families. Low sequence variation suggests selective pressure against sequence change in modern humans in contrast to the structural chromosomal and sequence changes including fixed X-Y differences that occurred in this region earlier in hominid evolution. Our findings exclude sequence variation in PCDHX/Y as relevant to the aetiology of psychosis. However, we note the unusual status of this region with respect to X-inactivation. Further investigation of the epigenetic control of PCDHX/Y in relation to psychosis is warrant

Item Type:Journal (Paginated)
Keywords:Psychosis; hominidae; laterality; language; sex chromosomes
Subjects:Neuroscience > Neurogenetics
ID Code:3879
Deposited By:Crow, Prof Tim
Deposited On:29 Nov 2004
Last Modified:11 Mar 2011 08:55

References in Article

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Bear D, Schiff D, Saver J, Greenberg M, Freeman R. 1986. Quantitative-analysis of cerebral asymmetries-fronto-occipital correlation, sexual dimorphism, and association with handedness. Arch Neurol 43: 598-603. Links

Blanco P, Sargent CA, Boucher CA, Mitchell M, Affara NA. 2000. Conservation of PCDHX in mammals; expression of human X/Y genes predominantly in brain. Mamm Genome 11: 906-914. Links

Burgoyne PS, McLaren A. 1985. Does X-Y pairing during male meiosis protect the paired region of the X-chromosome from subsequent X-inactivation? Hum Genet 70: 82-83. Links

Buxhoeveden D, Casanova M. 2000. Comparative lateralisation patterns in the language area of human, chimpanzee, and rhesus monkey brains. Laterality 5: 315-330. Links

Corballis MC, Lee K, McManus IC, Crow TJ. 1996. Location of the handedness gene on the X and Y chromosomes. Am J Med Genet 67: 50-52. Links

Crow TJ. 1993. Sexual selection, machiavellian intelligence, and the origins of psychosis. Lancet 342: 594-598. Links

Crow TJ. 1997. Is schizophrenia the price that homo sapiens pays for language? Schizophr Res 28: 127-141. Links

Crow TJ. 1999a. Schizophrenia as an epigenetic puzzle - in what sense were Gottesman and Shields correct? Mol Psychiatry 4: S18. Links

Crow TJ. 1999b. The case for an Xq21.3/Yp homologous locus in the evolution of language and the origins of psychosis. Acta Neuropsychiatrica 11: 54-56. Links

Crow TJ. 2002. Epigenetics of cerebral asymmetry as the determinant of disease expression. Schizophr Res 53: 25. Links

Crow TJ, Crow LR, Done DJ, Leask S. 1998. Relative hand skill predicts academic ability: Global deficits at the point of hemispheric indecision. Neuropsychologia 36: 1275-1282. Links

deCastro JMB, Arsuaga JL, Carbonell E, Rosas A, Martinez I, Mosquera M. 1997. A hominid from the lower Pleistocene of Atapuerca, Spain: Possible ancestor to Neanderthals and modern humans. Science 276: 1392-1395. Links

DeLisi LE, Mesen A, Rodriguez C, Bertheau A, LaPrade B, Llach M, Riondet S, Razi K, Relja M, Byerley W, Sherrington R. 2002. Genome-wide scan for linkage to schizophrenia in a Spanish-origin cohort from Costa Rica. Am J Med Genet 114: 497-508. Links

DeLisi LE, Shaw SH, Crow TJ, Shields G, Smith AB, Larach VW, Wellman N, Loftus J, Nanthakumar B, Razi K, Stewart J, Comazzi M, Vita A, Heffner T, Sherrington R. 2002. A genome-wide scan for linkage to chromosomal regions in 382 sibling pairs with schizophrenia or schizoaffective disorder. Am J Psychiatry 159: 803-812. Links

Hirano S, Yan Q, Suzuki ST. 1999. Expression of a novel protocadherin, OL-protocadherin, in a subset of functional systems of the developing mouse brain. J Neurosci 19: 995-1005. Links

Kumar S, Tamura K, Jakobsen IB, Nei M. 2001. MEGA2: Molecular evolutionary genetics analysis software. Bioinformatics 17: 1244-1245. Links

Lambson B, Affara NA, Mitchell M, Ferguson-Smith MA. 1992. Evolution of DNA-sequence homologies between the sex-chromosomes in primate species. Genomics 14: 1032-1040. Links

McGrew WC, Marchant LF. 1997. On the other hand: Current issues in and meta-analysis of the behavioral laterality of hand function in nonhuman primates. Yearbook Phys Anthropol 40: 201-232. Links

Nissim-Rafinia M, Kerem B. 2002. Splicing regulation as a potential genetic modifier. Trends Genet 18: 123-127. Links

Nollet F, Kools P, van Roy F. 2000. Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J Mol Biol 299: 551-572. Links

Sano K, Tanihara H, Heimark RL, Obata S, Davidson M, Stjohn T, Taketani S, Suzuki S. 1993. Protocadherins - a large family of cadherin-related molecules in central-nervous-system. EMBO J 12: 2249-2256. Links

Simonsen KL, Churchill GA, Aquadro CF. 1995. Properties of statistical tests of neutrality for DNA polymorphism data. Genetics 141: 413-429. Links

Suzuki ST. 2000. Recent progress in protocadherin research. Exp Cell Res 261: 13-18. Links

Tajima F. 1989a. Statistical-method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123: 585-595. Links

Tajima F. 1989b. The effect of change in population-size on DNA polymorphism. Genetics 123: 597-601. Links

Bear D, Schiff D, Saver J, Greenberg M, Freeman R. 1986. Quantitative-analysis of cerebral asymmetries-fronto-occipital correlation, sexual dimorphism, and association with handedness. Arch Neurol 43: 598-603. Links

Blanco P, Sargent CA, Boucher CA, Mitchell M, Affara NA. 2000. Conservation of PCDHX in mammals; expression of human X/Y genes predominantly in brain. Mamm Genome 11: 906-914. Links

Burgoyne PS, McLaren A. 1985. Does X-Y pairing during male meiosis protect the paired region of the X-chromosome from subsequent X-inactivation? Hum Genet 70: 82-83. Links

Buxhoeveden D, Casanova M. 2000. Comparative lateralisation patterns in the language area of human, chimpanzee, and rhesus monkey brains. Laterality 5: 315-330. Links

Corballis MC, Lee K, McManus IC, Crow TJ. 1996. Location of the handedness gene on the X and Y chromosomes. Am J Med Genet 67: 50-52. Links

Crow TJ. 1993. Sexual selection, machiavellian intelligence, and the origins of psychosis. Lancet 342: 594-598. Links

Crow TJ. 1997. Is schizophrenia the price that homo sapiens pays for language? Schizophr Res 28: 127-141. Links

Crow TJ. 1999a. Schizophrenia as an epigenetic puzzle - in what sense were Gottesman and Shields correct? Mol Psychiatry 4: S18. Links

Crow TJ. 1999b. The case for an Xq21.3/Yp homologous locus in the evolution of language and the origins of psychosis. Acta Neuropsychiatrica 11: 54-56. Links

Crow TJ. 2002. Epigenetics of cerebral asymmetry as the determinant of disease expression. Schizophr Res 53: 25. Links

Crow TJ, Crow LR, Done DJ, Leask S. 1998. Relative hand skill predicts academic ability: Global deficits at the point of hemispheric indecision. Neuropsychologia 36: 1275-1282. Links

deCastro JMB, Arsuaga JL, Carbonell E, Rosas A, Martinez I, Mosquera M. 1997. A hominid from the lower Pleistocene of Atapuerca, Spain: Possible ancestor to Neanderthals and modern humans. Science 276: 1392-1395. Links

DeLisi LE, Mesen A, Rodriguez C, Bertheau A, LaPrade B, Llach M, Riondet S, Razi K, Relja M, Byerley W, Sherrington R. 2002. Genome-wide scan for linkage to schizophrenia in a Spanish-origin cohort from Costa Rica. Am J Med Genet 114: 497-508. Links

DeLisi LE, Shaw SH, Crow TJ, Shields G, Smith AB, Larach VW, Wellman N, Loftus J, Nanthakumar B, Razi K, Stewart J, Comazzi M, Vita A, Heffner T, Sherrington R. 2002. A genome-wide scan for linkage to chromosomal regions in 382 sibling pairs with schizophrenia or schizoaffective disorder. Am J Psychiatry 159: 803-812. Links

Hirano S, Yan Q, Suzuki ST. 1999. Expression of a novel protocadherin, OL-protocadherin, in a subset of functional systems of the developing mouse brain. J Neurosci 19: 995-1005. Links

Kumar S, Tamura K, Jakobsen IB, Nei M. 2001. MEGA2: Molecular evolutionary genetics analysis software. Bioinformatics 17: 1244-1245. Links

Lambson B, Affara NA, Mitchell M, Ferguson-Smith MA. 1992. Evolution of DNA-sequence homologies between the sex-chromosomes in primate species. Genomics 14: 1032-1040. Links

McGrew WC, Marchant LF. 1997. On the other hand: Current issues in and meta-analysis of the behavioral laterality of hand function in nonhuman primates. Yearbook Phys Anthropol 40: 201-232. Links

Nissim-Rafinia M, Kerem B. 2002. Splicing regulation as a potential genetic modifier. Trends Genet 18: 123-127. Links

Nollet F, Kools P, van Roy F. 2000. Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J Mol Biol 299: 551-572. Links

Sano K, Tanihara H, Heimark RL, Obata S, Davidson M, Stjohn T, Taketani S, Suzuki S. 1993. Protocadherins - a large family of cadherin-related molecules in central-nervous-system. EMBO J 12: 2249-2256. Links

Simonsen KL, Churchill GA, Aquadro CF. 1995. Properties of statistical tests of neutrality for DNA polymorphism data. Genetics 141: 413-429. Links

Suzuki ST. 2000. Recent progress in protocadherin research. Exp Cell Res 261: 13-18. Links

Tajima F. 1989a. Statistical-method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123: 585-595. Links

Tajima F. 1989b. The effect of change in population-size on DNA polymorphism. Genetics 123: 597-601. Links

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