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Protocadherin X (PCDHX) and Y (PCDHY) genes; multiple mRNA isoforms encoding variant signal peptides and cytoplasmic domains

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Abstract

The gene-poor, hominid-specific Yp11.2/Xq21.3 X–Y homology block encodes two members of the protocadherin group of cell surface molecules, PCDHX and PCDHY. These two genes, mainly expressed in brain, were known to be composed of at least six exons sharing 98.1% DNA identity. The genomic structure of PCDHX/Y has been reanalyzed in detail, uncovering the existence of at least 11 more exons spanning more than 700 kb. Many of these exons located at the 5′ and 3′ ends of PCDHX/Y undergo differential and alternative splicing. Seven of the exons have been found to use alternative splice sites. Most of these variants are expressed within the brain, although some isoforms exhibit a more ubiquitous distribution pattern. PCDHX/Y transcription appears to be driven from two alternative promoters located usptream of exon 1 and exon 4.1. Assuming that the splicing events at the 5′ and 3′ ends of these genes are independent of one another, potentially up to 360 different mRNAs could be produced. The main impact on protein function is predicted to be in the efficiency of translation, post-translational processing within the cell, and structure of the cytoplasmic domain that may influence any role the genes have in signaling.

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Acknowledgements

This work was supported by the Medical Research Council, Sygen, and the Isaac Newton Trust. Sylvia Nyame provided preliminary sequence and expression data from the ESTs in the PCDHX/Y region. We thank María Giouzeli for sharing information about SNP discovery before publication.

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  1. Human Molecular Genetics Group, Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK

    Patricia Blanco-Arias, Carole A. Sargent & Nabeel A. Affara

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  1. Patricia Blanco-Arias
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  2. Carole A. Sargent
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  3. Nabeel A. Affara
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Correspondence to Nabeel A. Affara.

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Blanco-Arias, P., Sargent, C.A. & Affara, N.A. Protocadherin X (PCDHX) and Y (PCDHY) genes; multiple mRNA isoforms encoding variant signal peptides and cytoplasmic domains . Mamm Genome 15, 41–52 (2004). https://doi.org/10.1007/s00335-003-3028-7

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