Analysis of polyglutamine-coding repeats in the TATA-binding protein in different human populations and in patients with schizophrenia and bipolar affective disorder.
A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close to the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tractlengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus.
Rubinsztein
D C
DC
East Anglian Medical Genetics Service Molecular Genetics Laboratory, Addenbrooke's National Health Service Trust, Cambridge, United Kingdom.
Leggo
J
J
Crow
T J
TJ
DeLisi
L E
LE
Walsh
C
C
Jain
S
S
Paykel
E S
ES
D000349:Africa; D001714:Bipolar Disorder / Q000235:genetics*; D002524:Cerebellar Ataxia / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics*; D004739:England; D005006:Ethnicity / Q000235:genetics*; D005973:Glutamine; D006801:Humans; D006816:Huntington Disease / Q000235:genetics; D007194:India; D009134:Muscular Atrophy, Spinal / Q000235:genetics; D010455:Peptides; D011110:Polymorphism, Genetic; D044469:Racial Groups / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics*; D018911:Trinucleotide Repeats
D004268:DNA-Binding Proteins; D010455:Peptides; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D005973:Glutamine; C097188:polyglutamine