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Variation in the protocadherin gamma A gene cluster
George Kirov1, Lyudmila Georgieva, Nigel Williams
1Neuropsychiatric Genetics Unit, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK. kirov@cardiff.ac.uk
Genomics
|September 19, 2003
Summary
Genetic screening of protocadherin gamma A (PCDHGA) genes revealed a frameshift variant in PCDHGA8. This variant was initially more common in controls but lacked replication in independent samples, suggesting no strong association with schizophrenia.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- The protocadherin gene cluster on chromosome 5q31 plays a role in neural development and cell adhesion.
- Genetic variations in this cluster are being investigated for potential links to neurological disorders like schizophrenia.
Purpose of the Study:
- To screen for genetic variations within the 12 protocadherin gamma A (PCDHGA) genes.
- To investigate the association of identified variants, particularly in PCDHGA8, with schizophrenia.
Main Methods:
- Denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing was used to screen for variations.
- Genotyping of pooled DNA and analysis of transmission in trios were employed to assess case-control association and segregation.
Main Results:
- Twenty-four nonsynonymous changes, 24 synonymous SNPs, and 9 polymorphisms in 5' flanking regions were identified.
- A frameshift variant (Pro174fsdelC) in PCDHGA8 showed initial higher frequency in controls (10.6%) versus schizophrenia cases (7.2%, p=0.007).
- This association was not replicated in an independent trio sample (p=0.43), and 10 common polymorphisms showed no significant association with schizophrenia.
Conclusions:
- The identified frameshift variant in PCDHGA8 does not appear to be a significant risk factor for schizophrenia.
- Further research is needed to determine the phenotypic consequences of PCDHGA8 loss-of-function variants.