Alteration of branch site consensus sequence and enhanced pre-mRNA splicing of an NMDAR1 intron not associated with schizophrenia.
Am J Med Genet
; 114(6): 631-6, 2002 Aug 08.
Article
em En
| MEDLINE
| ID: mdl-12210277
ABSTRACT
Aberrant splicing of pre-mRNA is recognized to account for a significant minority of disease-causing mutations. The N-methyl-D-aspartate receptor (NMDA) subunit gene R1 (NMDAR1) is alternatively spliced to produce eight length variants. In an examination of the NMDAR1 as a candidate gene in schizophrenia, a presumed microdeletion/insertion (del/ins) was observed in intron 10 of an African-American male near a weak putative branch-site consensus sequence. Although exon 10 is not known to be alternatively spliced, the del/ins was posited to alter splicing efficiency. If splicing were abolished and intron retention occurred, an in-frame translation product of more than 250 amino acids was predicted. To explore splicing efficiency, mini genes were examined through primer-extension analyses in NIH293 embryonic kidney cell cultures. Rather than disruption of splicing, the del/ins allele exhibited a fivefold enhancement in splicing. In an association analysis with additional schizophrenic cases and unaffected controls, all of African-American descent, the mutant allele was observed at equivalent frequencies. A family study also did not support cosegregation of the variant allele with psychiatric disease.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
RNA Mensageiro
/
Precursores de RNA
/
Íntrons
/
Processamento Alternativo
/
Receptores de N-Metil-D-Aspartato
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Am J Med Genet
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos