title: Variation in the protocadherin gamma A gene cluster.
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.
mesh_terms: D000595:Amino Acid Sequence; D015820:Cadherins / Q000145:classification / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D002895:Chromosomes, Human, Pair 5; D016368:Frameshift Mutation; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D005810:Multigene Family; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D015820:Cadherins