Inactivation status of PCDH11X: sexual dimorphisms in gene expression levels in brain

Lopes, Alexandra M.; Ross, Norman; Close, James; Dagnall, Adam; Amorim, António; Crow, Timothy J.

doi:10.1007/s00439-006-0134-0

Cited by 49 publications

(47 citation statements)

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“…However, it is of interest that microarray hybridization has shown elevated expression of PCDH11XY mRNA in lymphocytes from individuals with four or five X chromosomes [Sudbrak et al, 2001]. Moreover, using PCDH11X-specific primers for RT-PCR Lopes et al [2006] have shown that expression of the X allele is twofold greater in XX females than XY males and concluded that the gene escapes X inactivation. Expression of PCDH11Y was not examined by Lopes et al [2006], but there is evidence from other work [Blanco et al, 2000] that PCDH11Y is also expressed in the brain.…”

Section: Ggactcagcttttgggaact 55mentioning

confidence: 97%

“…1) are not methylated. Bisulfite sequencing of genomic DNA from 4 KS and 2 KS-PSY individuals carried out essentially as described by Lopes et al [2006] showed that the percentage of methylated CpGs in all clones examined ranged from 0 to 7% for fragment A (CpGs 1-16) and 0-3% for fragment B (CpGs 17-22). Data were obtained by sequencing a total of 20 clones (360 CpGs) from fragment A and 22 clones (132 CpGs) from fragment B.…”

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confidence: 99%

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Methylation of twoHomo sapiens‐specific X‐Y homologous genes in Klinefelter's syndrome (XXY)

Ross

Wadekar

Lopes

et al. 2006

American J of Med Genetics Pt B

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An increased incidence of psychiatric and structural brain abnormalities in individuals with Klinefelter syndrome (KS, 47 XXY) could be due to the presence of extra copies of X-Y homologous genes that escape X inactivation. Of particular interest are the two brain-expressed genes Protocadherin11XY (PCDH11XY) and the Synaptobrevin-like gene (SYBL1) which have been duplicated from the X chromosome to the Y chromosome to give X-Y homologous gene pairs that are specific to modern humans. We examined the DNA of KS individuals reported recently by DeLisi et al. 2005 and determined the parental origin of the X alleles, the degree of skewed X inactivation and investigated the CpG island methylation status of PCDH11XY and SYBL1 by bisulphite sequencing and quantification of methylated HpaII sites. We used a novel method for quantification of unmethylated CpGs with the restriction enzyme McrBC which cuts methylated but not unmethylated CpGs. The results showed that KS individuals have two methylated and one unmethylated SYBL1 allele whereas PCDH11XY is unmethylated and escapes X inactivation on the extra X chromosome. Overexpression of PCDH11XY in KS is probable and variable escape from inactivation of this Homo sapiens-specific gene could account for some abnormalities in KS. The origin of the parental alleles or their preferential X inactivation was not associated with psychotic symptoms.

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Section: Ggactcagcttttgggaact 55mentioning

confidence: 97%

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confidence: 99%

Methylation of twoHomo sapiens‐specific X‐Y homologous genes in Klinefelter's syndrome (XXY)

Ross

Wadekar

Lopes

et al. 2006

American J of Med Genetics Pt B

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“…Expression profiles and alternative transcripts of PCDH11X/Y gene with various brain region samples have been investigated [Blanco et al, 2000[Blanco et al, , 2003. Human females display higher levels of PCDH11X gene expression in brain tissues than males [Lopes et al, 2006]. Different cassette exons of PCDH11X/Y could affect the human brain differentially in males and females by virtue of this different expression activity.…”

Section: Discussionmentioning

confidence: 97%

“…Reverse transcription-polymerase chain reaction (RT-PCR) amplification has been used to quantify expression of alternative transcripts of PCDH11X/Y genes in sub-regions of brain and various other human tissues [Blanco et al, 2000]. Transcription activity of the PCDH11X gene in females exceeds that in males twofold, and the CpG islands of PCDH11X/Y are not methylated in humans and chimpanzees [Lopes et al, 2006]. Fluorescence in situ hybridization analysis using PCDH11X/Y specific probe has demonstrated no signals in the chimpanzee and gorilla Y chromosome [Wilson et al, 2006].…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of alternative transcripts of human PCDH11X/Y genes

Ahn

Huh

Kim

et al. 2009

American J of Med Genetics Pt B

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The Protocadherin 11X/Y (PCDH11X/Y) gene pair has been proposed as a carrier of the variation relating to cerebral asymmetry and psychosis on the ground that the Y gene was generated by duplication at 6 million years (close to the chimpanzee-human separation) and there is a case for an X/Y determinant of cerebral asymmetry. The present article investigated the patterns of alternative splicing and expression of the PCDH11X/Y genes. Twelve alternative transcripts of PCDH11X/Y genes were presently identified by in silico analysis. To investigate the biological roles of alternative transcripts of PCDH11X/Y genes, the transcripts were analyzed by real-time reverse transcription-polymerase chain reaction amplification. A total of 31 normal tissues including 11 different regions of human brain were used to investigate a wide spectrum of expression profiles. Dominant expression patterns were identified in several tissues (Tx1-fetal liver; Tx3-adult brain; Tx4-adult brain and kidney; Tx5-bone marrow; Ty1-fetal brain; Ty2-adrenal gland). Tx4 transcripts showed specific expression patterns in olfactory tissues. The findings can guide functional investigation of neuropsychiatric disorders.

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“…Para estos investigadores el candidato más idóneo sería el gen de la protocadherina 11, del que existen, consecuentemente, dos variantes, una ligada a X (PCDHX [PCDH11X]), localizada en Xq21.3, y otra ligada a Y (PCDHY [PCDH11Y]), localizada en Yp11.2, pero cuya identidad alcanza el 98.3% a nivel amioacídico (Blanco et al, 2000). La expresión de ambos genes sería diferente en los dos sexos, puesto que el gen PCDHX [PCDH11X] escapa, en particular, al proceso general de inactivación que afecta característicamente a los genes contenidos en el cromosoma X, de ahí que sus niveles de expresión en los individuos de sexo femenino dupliquen los observados en los de sexo masculino (Lopes et al, 2006). El gen PCDHY [PCDH11Y] es el resultado de un proceso de transposición al cromosoma Y de una copia del gen PCDHX [PCDH11X], el cual tuvo lugar hace entre tres y cuatro millones de años, tras la separación de la línea evolutiva que condujo a la aparición de la especie humana de la que dio lugar a las restantes especies actuales de primates (Sargent et al, 1996), de ahí que esté ausente en dichas especies (Wilson et al, 2006) y que no se observe en ellas la disparidad sexual en el grado de lateralización, ni consecuentemente de habilidad manual, que aparece característicamente en nuestra especie.…”

Section: ¿Existen Otras Evidencias Al Margen De Las De Tipo Fósil Capunclassified

La lateralización cerebral y el origen del lenguaje

Benítez‐Burraco¹

2007

ELUA

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ResumenEl "órgano del lenguaje" se encuentra lateralizado en términos estructurales y funcionales. Se ha prestado una especial atención a aquellas evidencias fósiles que parecen sugerir la existencia en especies de homínidos extintas de una lateralización cerebral de carácter estructural y funcional semejante a la que se advierte en los humanos, que podrían ser un indicio de la disponibilidad de una (cierta) capacidad de procesamiento lingüístico. Evidencias adicionales han aportado nuevos datos sobre los principales hitos que habrían jalonado dicho itinerario evolutivo, en particular, en lo que concierne a la cuestión de la lateralización y su relación con el lenguaje. El objetivo de este trabajo es tratar de valorar críticamente todas estas evidencias, así como las inferencias realizadas a partir de ellas sobre las capacidades lingüísticas de otras especies de homínidos. La conclusión fundamental será que, mientras que las evidencias fósiles parecen enfrentarse a dificultades inherentes a la asunción de una homología funcional, allí donde parece existir (sólo) una homología estructural, las evidencias de naturaleza molecular parecen asumir una concepción demasiado simplista de las relaciones que se establecen entre los genes y la cognición. El artículo concluirá bosquejando un modelo evolutivo general del "órgano del lenguaje" más ajustado al creciente corpus de datos genéticos y moleculares. PALABRAS CLAVE: lateralización cerebral, evidencias fósiles, biología molecular, evolución del lenguaje AbstractThe "language organ" seems to be lateralised both structurally and functionally. When trying to discern how language evolved, fossil evidences concerning structural and functional brain lateralization have been regularly considered, and a (rudimentary) language faculty have tentatively been inferred for some extinct hominid species. Further evidences, mainly concerning brain gene evolution, have also been recently taken into account when trying to determine phylogenetic relationships between brain lateralization and language. This growing body of evidences are critically examined in this paper. A main conclusion will be that fossil evidences often lead to wrongly infer functional homology from structural homology, whereas molecular data are frequently linked to simplistic conceptions of the genuine connection between genes and cognition. Consequently, a tentative model for accounting the evolution of the language organ will be outlined, mainly based on genetic and molecular data.

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Inactivation status of PCDH11X: sexual dimorphisms in gene expression levels in brain

Cited by 49 publications

References 52 publications

Methylation of twoHomo sapiens‐specific X‐Y homologous genes in Klinefelter's syndrome (XXY)

Methylation of twoHomo sapiens‐specific X‐Y homologous genes in Klinefelter's syndrome (XXY)

Quantitative analysis of alternative transcripts of human PCDH11X/Y genes

La lateralización cerebral y el origen del lenguaje

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