Mutational analysis of two positional candidate susceptibility genes for bipolar disorder on chromosome 12q23-q24: phenylalanine hydroxylase and human LIM-homeobox LHX5.
OBJECTIVE
In the search for chromosome 12 genes potentially involved in the pathogenesis of bipolar disorder we will screen Phenylalanine hydroxylase and human LIM-homeobox LHX5 genes for sequence variants, both of which have been suggested as candidate genes. The genes lie on chromosome 12q23-24, near the Darier's disease gene, ATP2A2. We have previously reported two families in which the pattern of segregation of illness is consistent with genetic linkage between this chromosomal region and a putative highly penetrant autosomal dominant major affective disorder locus (pedigree 324, maximum LOD=2.1; pedigree 5501, maximum LOD=3.6).


METHODS
We screened the coding and intronic flanking regions of the phenylalanine hydroxylase and LHX5 genes for sequence variation by denaturing high-performance liquid chromatography in individuals from the pedigrees.


RESULTS
In total, nine single nucleotide polymorphisms and one 6 base pair deletion were identified.


CONCLUSIONS
Our studies allowed us to conclude that none of these variants act as a highly penetrant autosomal dominant susceptibility locus for mood disorder in our families.
Green
Elaine K
EK
Molecular Psychiatry Group, Division of Neuroscience, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Birmingham, UK.
Elvidge
Gareth P
GP
Owen
Michael J
MJ
Craddock
Nick
N
D001483:Base Sequence; D044383:Black People / Q000235:genetics; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D060850:LIM-Homeodomain Proteins; D008126:Lod Score; D008297:Male; D019964:Mood Disorders / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014157:Transcription Factors; D016335:Zinc Fingers / Q000235:genetics
D017931:DNA Primers; D018398:Homeodomain Proteins; C491186:LHX5 protein, human; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D010651:Phenylalanine Hydroxylase