Motoki N Tada | PubMed Health

PubMed2005

Identification and characterization of coding single-nucleotide polymorphisms within human protocadherin-alpha and -beta gene clusters.

The human protocadherin (Pcdh) gene clusters are located on chromosome 5q31. Single-nucleotide polymorphisms (SNPs) were detected in the Pcdh-alpha and -beta variable exons, and in the Pcdh-alpha constant exon, in samples from 104 individuals. Among coding SNPs (cSNPs), nonsynonymous (amino acid exchange) SNPs were 2.2 times more common than synonymous (silent) changes in the Pcdh-alpha variable exons, but only 1.2 times more common in the Pcdh-beta variable exons. The nonsynonymous SNPs were high in the ectodomain (EC) 1 encoding region of Pcdh-alpha but not of Pcdh-beta. One 48-kb region of extensive linkage disequilibrium (LD) is reported that has two haplotypes extending from the alpha1 to alpha7 genes in the Pcdh-alpha cluster. Here we identified 15 amino acid exchanges in these two major haplotypes; therefore, the two haplotypes encode different sets of Pcdh-alpha proteins in the brain. The distribution of cSNPs was different for each EC region of Pcdh-alpha or -beta. The frequency of cSNPs was negatively correlated with the paralogous sequence diversity. These results suggested that gene conversion events in homologous regions of the Pcdh-alpha and Pcdh-beta clusters generated the cSNPs. Within the cSNPs, gene conversions were found in Pcdh-alpha4 in the major haplotype, and in Pcdh-beta9. These gene conversions were caused by the unequal crossing-over of homologous sequence regions. Thus, nonsynonymous variations in the Pcdh-alpha and -beta genes are possible contributors to the variations in human brain function.

Alleles↗

PubMed2004

Genomic organization and transcripts of the zebrafish Protocadherin genes.

We have examined the protocadherin (Pcdh) gene clusters of the zebrafish (Danio rerio). At least three sets of the Pcdh gene cluster were found in the zebrafish genome. Here, we describe the complete organization of the DrPcdh2 gene clusters. Classification by phylogenetic and transcript analyses revealed 7 DrPcdh2omicron, 20 DrPcdh2alphaa, 12 DrPcdh2alphab, and 1 DrPcdh2alphac variable exons upstream of the DrPcdh2alpha constant region exons in the DrPcdh2 gene cluster. The constant regions of the DrPcdh1alpha and DrPcdh2alpha genes in zebrafish were orthologs of those of the mammalian Pcdhalpha. These exons all encoded plural PXXP motifs in their cytoplasmic tails. The sequences of the variable exons were highly conserved within each family: DrPcdh2omicron, DrPcdh2alphaa, and DrPcdh2alphab. Transcript analysis revealed that zebrafish Pcdhs had alternatively spliced variants in the constant region that were not found in mammals. More gene clusters, more variable exons, and more alternative splicing variants were found in zebrafish than in mammals. Thus, although the Pcdhalpha families were common to diverse vertebrates, their gene number, structure, and transcripts were different between teleosts and mammals.

Alternative Splicing↗