A novel polymorphism in exon 11 of the WKL1 gene, shows no association with schizophrenia.
A missense mutation in exon 11 of the WKL1 gene on chromosome 22 was found to be associated with cases of catatonic schizophrenia in a single large pedigree. We have screened exon 11 of the WKL1 gene in 174 cases of schizophrenia, including cases of 22 cases of catatonic schizophrenia, but could not detect the previously reported mis-sense mutation. However in exon 11, we observed an insertion/deletion polymorphism, one-missense substitution and two synonymous substitutions. In addition, we also identified a nucleotide substitution in intron 11. All these polymorphisms appeared to be in complete linkage disequilibrium with one another. The polymorphisms were also identified in a UK pedigree with schizophrenia, however the polymorphisms did not segregate with the disease. To test for potential association between these polymorphisms and schizophrenia we sequenced an equal number of UK control individuals who were free of all psychiatric symptoms and had negative family histories for mental illness; the frequency of the insertion/deletion polymorphism was not significantly different in schizophrenia cases (42 out of 348 chromosomes, allele frequency 12%) compared to normal controls (40 out of 356 chromosomes, allele frequency 11%). The insertion/deletion was found to be in Hardy Weinberg equilibrium in both the schizophrenic and control groups. The insertion/deletion is composed of repeated sequence from exon 11 and intron 11 and is predicted to affect WKL1 protein structure.
McQuillin
Andrew
A
Molecular Psychiatry Laboratory, University College London, Department of Psychiatry & Behavioural Sciences, Windeyer Institute of Medical Sciences, 46 Cleveland Street, London W1T 4JF, UK.
Kalsi
Gursharan
G
Moorey
Helen
H
Lamb
Graham
G
Mayet
Soraya
S
Quested
Digby
D
Baker
Philip
P
Curtis
David
D
Gurling
Hugh Malcolm
HM
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D004251:DNA Transposable Elements; D005091:Exons; D006801:Humans; D007438:Introns; D007473:Ion Channels / Q000235:genetics*; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D011110:Polymorphism, Genetic; D012016:Reference Values; D012559:Schizophrenia / Q000235:genetics*; D017384:Sequence Deletion; D006113:United Kingdom
D004251:DNA Transposable Elements; D007473:Ion Channels; C431249:WKL1 cation channel