Mutational analysis of phospholipase A2A: a positional candidate susceptibility gene for bipolar disorder.
Evidence for the involvement of genetic factors in the pathogenesis of bipolar affective disorder is now well established. However, the mode of inheritance is non-mendelian and this makes the identification of susceptibility loci difficult. A short-cut to localisation of a disease gene for an oligogenic/multifactorial disorder such as bipolar disorder may come from observation of cosegregation with a monogenic trait. We have described a family (pedigree 324) in which there was cosegregation of major affective disorder and Darier's disease, a dominantly inherited skin disorder, and hypothesised that this reflects genetic linkage between genes involved in these disorders. Genetic mapping studies have placed the locus for Darier's disease on chromosome 12q23-q24. We conducted subsequent linkage studies (1995) upon 45 bipolar families (without Darier's disease). These results showed some evidence in favour of linkage with chromosome 12q markers with maximum evidence at a trinucleotide repeat marker within intron 1 of the phospholipase A2A (PLA2A) gene. Evidence for linkage was more significant when analysing the 22 families comprising the Cardiff centre sample, which were expected to be most genetically similar to pedigree 324.
Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK. jacobsen@cardiff.ac.uk
N J
NJ
Jacobsen
E K
EK
Franks
M J
MJ
Owen
N J
NJ
Craddock
D000328:Adult; D001714:Bipolar Disorder / Q000201:enzymology / Q000235:genetics*; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D004252:DNA Mutational Analysis; D007644:Darier Disease / Q000201:enzymology / Q000235:genetics; D005091:Exons; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010741:Phospholipases A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values; D015183:Restriction Mapping
D005819:Genetic Markers; D010741:Phospholipases A