Exclusion of DNA changes in the beta-subunit of the c-GMP phosphodiesterase gene as the cause for Huntington's disease.
To identify expressed sequences within candidate regions for the Huntington's disease (HD) gene in 4p16.3, we isolated the gene encoding the beta subunit of the human cGMP phosphodiesterase (PDEB). We formally assessed this as a candidate gene for HD based on it's expression in brain, the demonstration of linkage disequilibrium between intragenic DNA markers and HD, and the demonstration that mice with a mutation in this gene have a reduction of neurons in particular brain regions. We investigated all 22 exons of PDEB and 5'-flanking region for point mutations in 16 HD patients of different ethnic origins using single strand conformational polymorphism analysis. The underlying DNA changes found initially exclusively in HD patients were excluded as the cause for HD.
Riess
O
O
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Noerremoelle
A
A
Collins
C
C
Mah
D
D
Weber
B
B
Hayden
M R
MR
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D006816:Huntington Disease / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic
D004247:DNA; D015106:3',5'-Cyclic-GMP Phosphodiesterases