Comparative DNA sequence analysis of mouse and human protocadherin gene clusters

Wu, Q., Zhang, T., Cheng, J. F., Kim, Y., Grimwood, J., Schmutz, J., Dickson, M., Noonan, J. P., Zhang, M. Q., Myers, R. M., Maniatis, T. (March 2001) Comparative DNA sequence analysis of mouse and human protocadherin gene clusters. Genome Research, 11 (3). pp. 389-404. ISSN 1088-9051

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URL: http://www.ncbi.nlm.nih.gov/pubmed/11230163

Abstract

The genomic organization of the human protocadherin alpha, beta, and gamma gene clusters (designated Pcdh alpha [gene symbol PCDHA], Pcdh beta [PCDHB], and Pcdh gamma [PCDHG]) is remarkably similar to that of immunoglobulin and T-cell receptor genes. The extracellular and transmembrane domains of each protocadherin protein are encoded by an unusually large "variable" region exon, while the intracellular domains are encoded by three small "constant" region exons located downstream from a tandem array of variable region exons. Here we report the results of a comparative DNA sequence analysis of the orthologous human (750 kb) and mouse (900 kb) protocadherin gene clusters. The organization of Pcdh alpha and Pcdh gamma gene clusters in the two species is virtually identical, whereas the mouse Pcdh beta gene cluster is larger and contains more genes than the human Pcdh beta gene cluster. We identified conserved DNA sequences upstream of the variable region exons, and found that these sequences are more conserved between orthologs than between paralogs. Within this region, there is a highly conserved DNA sequence motif located at about the same position upstream of the translation start codon of each variable region exon. In addition, the variable region of each gene cluster contains a rich array of CpG islands, whose location corresponds to the position of each variable region exon. These observations are consistent with the proposal that the expression of each variable region exon is regulated by a distinct promoter, which is highly conserved between orthologous variable region exons in mouse and human.

Item Type: Paper
Uncontrolled Keywords: CADHERIN SUPERFAMILY CPG ISLANDS GENOMIC ORGANIZATION OL-PROTOCADHERIN DIVERSITY ADHESION REGION FAMILY IDENTIFICATION EMBRYOS
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
CSHL Authors:
Communities: CSHL labs > Zhang lab
Depositing User: Matt Covey
Date: March 2001
Date Deposited: 15 Jan 2014 20:12
Last Modified: 15 Jan 2014 20:12
PMCID: PMC311048
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29331

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