Recombination as a mechanism for sporadic mutation in the surfactant protein-C gene.
Pediatr Pulmonol
; 43(5): 443-50, 2008 May.
Article
em En
| MEDLINE
| ID: mdl-18383112
ABSTRACT
OBJECTIVE:
To determine haplotype background of common mutations in the genes encoding surfactant proteins B and C (SFTPB and SFTPC) and to assess recombination in SFTPC. STUDYDESIGN:
Using comprehensive resequencing of SFTPC and SFTPB, we assessed linkage disequilibrium (LD) (D'), and computationally inferred haplotypes. We computed average recombination rates and Bayes factors (BFs) within SFTPC in a population cohort and near SFTPC (+/-50 kb) in HapMap cohorts. We then biochemically confirmed haplotypes in families with sporadic SFTPC mutations (n = 11) and in individuals with the common SFTPB mutation (121ins2, n = 30).RESULTS:
We detected strong evidence (weak LD and BFs > 1,400) for an intragenic recombination hot spot in both genes. The 121ins2 SFTPB mutation occurred predominantly (89%) on 2 common haplotypes. In contrast, no consistent haplotypes were associated with mutated SFTPC alleles. Sporadic SFTPC mutations arose on the paternal allele in four of five families; the remaining child had evidence for somatic recombination on the mutated allele.CONCLUSIONS:
In contrast to SFTPB, disease alleles at SFTPC do not share a common haplotype background. Most sporadic mutations in SFTPC occurred on the paternal allele, but somatic recombination may be an important mechanism of mutation in SFTPC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recombinação Genética
/
Doenças Pulmonares Intersticiais
/
Proteína C Associada a Surfactante Pulmonar
/
Mutação
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
/
Infant
Idioma:
En
Revista:
Pediatr Pulmonol
Assunto da revista:
PEDIATRIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos