Variation in the protocadherin gamma A gene cluster

Genomics. 2003 Oct;82(4):433-40. doi: 10.1016/s0888-7543(03)00167-8.

Abstract

We screened for variation in the 12 protocadherin gamma A (PCDHGA) genes of the protocadherin cluster on chromosome 5q31. We used denaturing high-performance liquid chromatography followed by sequencing to identify changes in the DNA sequence. We identified 24 nonsynonymous changes, 24 synonymous SNPs, and 9 polymorphisms in the 5' flanking regions. The variant with the greatest predicted impact on the encoded protein was a frameshift polymorphism in PCDHGA8, caused by a deletion of one C base (Pro174fsdelC). The del variant was more common in 512 controls compared to 506 schizophrenic (SZ) cases (10.6% vs 7.2%, p=0.007) but this trend was not replicated in an independent sample of 403 trios, in which it was transmitted 47 times and not transmitted 55 times from heterozygous parents (p=0.43). We screened 10 of the common polymorphisms for association with schizophrenia by genotyping pooled DNA from 540 SZ cases and 540 controls, but none of them showed a significant difference. It will be important to identify the phenotype associated with the loss of the PCDHGA8 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cadherins / classification
  • Cadherins / genetics*
  • Chromatography, High Pressure Liquid
  • Chromosomes, Human, Pair 5
  • Frameshift Mutation
  • Genetic Testing / methods*
  • Genetic Variation*
  • Humans
  • Linkage Disequilibrium
  • Molecular Sequence Data
  • Multigene Family*
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Schizophrenia / genetics
  • Sequence Alignment

Substances

  • Cadherins