Identification and characterization of coding single-nucleotide polymorphisms within human protocadherin-α and -β gene clusters

The human protocadherin ( Pcdh) gene clusters are located on chromosome 5q31. Single-nucleotide polymorphisms (SNPs) were detected in the Pcdh-α and -β variable exons, and in the Pcdh-α constant exon, in samples from 104 individuals. Among coding SNPs (cSNPs), nonsynonymous (amino acid exchange) SNP...

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Bibliographic Details
Published in:Gene 2005-04, Vol.349, p.1-14
Main Authors: Miki, Rie, Hattori, Kotaro, Taguchi, Yusuke, Tada, Motoki N., Isosaka, Tomoko, Hidaka, Yuko, Hirabayashi, Takahiro, Hashimoto, Ryota, Fukuzako, Hiroshi, Yagi, Takeshi
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Sequence
Amino Acid Substitution
Asian Continental Ancestry Group
Brain
Brain - physiology
Cadherin
Cadherins - chemistry
Cadherins - genetics
Chromosome Mapping
Chromosomes, Human, Pair 5
CNR
Conserved Sequence
DNA - blood
DNA - genetics
Evolution, Molecular
Exons
Gene Conversion
Gene Frequency
Genetic Variation
Haplotypes
Humans
Linkage Disequilibrium
Molecular Sequence Data
Multigene Family
Phylogeny
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Protein Structure, Tertiary
Sequence Analysis, DNA
Sequence Deletion
Sequence Homology, Amino Acid
SNP
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Summary:The human protocadherin ( Pcdh) gene clusters are located on chromosome 5q31. Single-nucleotide polymorphisms (SNPs) were detected in the Pcdh-α and -β variable exons, and in the Pcdh-α 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-α variable exons, but only 1.2 times more common in the Pcdh-β variable exons. The nonsynonymous SNPs were high in the ectodomain (EC) 1 encoding region of Pcdh-α but not of Pcdh-β. One 48-kb region of extensive linkage disequilibrium (LD) is reported that has two haplotypes extending from the α1 to α7 genes in the Pcdh-α cluster. Here we identified 15 amino acid exchanges in these two major haplotypes; therefore, the two haplotypes encode different sets of Pcdh-α proteins in the brain. The distribution of cSNPs was different for each EC region of Pcdh-α or -β. 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-α and Pcdh-β clusters generated the cSNPs. Within the cSNPs, gene conversions were found in Pcdh-α4 in the major haplotype, and in Pcdh-β9. These gene conversions were caused by the unequal crossing-over of homologous sequence regions. Thus, nonsynonymous variations in the Pcdh-α and -β genes are possible contributors to the variations in human brain function.
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2004.11.044