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 M. Nogee, Howard Henderson, F. Sessions Cole, Aaron Hamvas

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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
Pages (from-to)443-450
Number of pages8
JournalPediatric Pulmonology
Issue number5
StatePublished - May 2008


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


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