Recombination as a mechanism for sporadic mutation in the surfactant protein-C gene

Amy D. McBee, Daniel J. Wegner, Christopher S. Carlson, Jennifer A. Wambach, Ping Yang, Hillary B. Heins, Ola D. Saugstad, Michelle A. Trusgnich, Julie Watkins-Torry, Lawrence Nogee, Howard Henderson, F. Sessions Cole, Aaron Hamvas

Research output: Contribution to journalArticle

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. Study Design: 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.

Original languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalPediatric Pulmonology
Volume43
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Protein C
Surface-Active Agents
Genetic Recombination
Haplotypes
Mutation
Alleles
Genes
Linkage Disequilibrium
HapMap Project
Population

Keywords

  • Children
  • Genetics
  • Haplotype
  • Interstitial lung disease
  • Linkage disequilibrium

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

McBee, A. D., Wegner, D. J., Carlson, C. S., Wambach, J. A., Yang, P., Heins, H. B., ... Hamvas, A. (2008). Recombination as a mechanism for sporadic mutation in the surfactant protein-C gene. Pediatric Pulmonology, 43(5), 443-450. https://doi.org/10.1002/ppul.20782

Recombination as a mechanism for sporadic mutation in the surfactant protein-C gene. / McBee, Amy D.; Wegner, Daniel J.; Carlson, Christopher S.; Wambach, Jennifer A.; Yang, Ping; Heins, Hillary B.; Saugstad, Ola D.; Trusgnich, Michelle A.; Watkins-Torry, Julie; Nogee, Lawrence; Henderson, Howard; Cole, F. Sessions; Hamvas, Aaron.

In: Pediatric Pulmonology, Vol. 43, No. 5, 05.2008, p. 443-450.

Research output: Contribution to journalArticle

McBee, AD, Wegner, DJ, Carlson, CS, Wambach, JA, Yang, P, Heins, HB, Saugstad, OD, Trusgnich, MA, Watkins-Torry, J, Nogee, L, Henderson, H, Cole, FS & Hamvas, A 2008, 'Recombination as a mechanism for sporadic mutation in the surfactant protein-C gene', Pediatric Pulmonology, vol. 43, no. 5, pp. 443-450. https://doi.org/10.1002/ppul.20782
McBee AD, Wegner DJ, Carlson CS, Wambach JA, Yang P, Heins HB et al. Recombination as a mechanism for sporadic mutation in the surfactant protein-C gene. Pediatric Pulmonology. 2008 May;43(5):443-450. https://doi.org/10.1002/ppul.20782
McBee, Amy D. ; Wegner, Daniel J. ; Carlson, Christopher S. ; Wambach, Jennifer A. ; Yang, Ping ; Heins, Hillary B. ; Saugstad, Ola D. ; Trusgnich, Michelle A. ; Watkins-Torry, Julie ; Nogee, Lawrence ; Henderson, Howard ; Cole, F. Sessions ; Hamvas, Aaron. / Recombination as a mechanism for sporadic mutation in the surfactant protein-C gene. In: Pediatric Pulmonology. 2008 ; Vol. 43, No. 5. pp. 443-450.
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