Quantitative analysis of alternative transcripts of human PCDH11X/Y genes

Abstract

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.

Regulation of Wnt signaling by protocadherins

“…PcdhX/Y ; a Pcdh11 gene is found on the homologous region of both the X and Y chromosomes in humans, but only on the X chromosome in other mammals; [100]), the EC domains of which are encoded by 2 exons [91]. While alternative splicing of small exons is observed in all δ1-Pcdh transcripts, this is particularly prominent within Pcdh11 and Pcdh19 , resulting in numerous splice variants for these genes [91, 101–103]. …”

Comparative Analysis of Protocadherin-11 X-Linked Expression among Postnatal Rodents, Non-Human Primates, and Songbirds Suggests Its Possible Involvement in Brain Evolution

“…These subtle differences might affect brain functions. With regard to the human brain, there are limited data available on Pcdh11X expression patterns [12], [34]–[38]. Further detailed studies in postmortem human brains, or other primate species, are necessary to further examine this possibility.…”

Protocadherin 11X/Y a Human-Specific Gene Pair: an Immunohistochemical Survey of Fetal and Adult Brains

“…Ex6 immunoreactivity is ameliorated by incubation with the recombinant PCDH11Ya cytoplasmic protein suggesting specificity to a Y motif, but the high similarity between PCDH11Ya and PCDH11Xb within the cytodomain (and indeed the entire protein) makes it difficult to design antibodies and nucleotide probes that differentiate the PCDH11X and PCDH11Y. This is also a problem for longer isoforms, for example, a report of upregulation of PCDH11Xc in males using microarrays (Galfalvy et al 2003) is dubious given that the probesets in question are 100% identical to PCDH11Yc (Lopes et al 2006; Weickert et al 2009) and, in another report, 3 PCDH11Y isoform-specific primer pairs produced product from female tissues (Ahn et al 2010). To avoid such cross-reactivity, studies have isolated small fragments that exploit the few PCDH11X/Y sequence differences (Giouzeli et al 2004) or used common riboprobes (Dibbens et al 2008) or pan PCDH11X/Y antibodies (Chen et al 2002) to examine PCDH11X/Y as a whole.…”