Comprehensive genetic variant discovery in the surfactant protein B gene

Aaron Hamvas, Daniel J. Wegner, Christopher S. Carlson, Kelly R. Bergmann, Michelle A. Trusgnich, Lucinda Fulton, Yumi Kasai, Ping An, Elaine R. Mardis, Richard K. Wilson, F. Sessions Cole*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Completely penetrant mutations in the surfactant protein B gene (SFTPB) and >75% reduction of SFTPB expression disrupt pulmonary surfactant function and cause neonatal respiratory distress syndrome. To inform studies of genetic regulation of SFTPB expression, we created a catalogue of SFTPB variants by comprehensive resequencing from an unselected, population-based cohort (n = 1,116). We found an excess of low-frequency variation [81 SNPs and five small insertion/deletions (in/dels)]. Despite its small genomic size (9.7 kb), SFTPB was characterized by weak linkage disequilibrium (LD) and high haplotype diversity. Using the HapMap Yoruban and European populations, we identified a recombination hot spot that spans SFTPB, was not detectable in our focused resequencing data, and accounts for weak LD. Using homology-based software tools, we discovered no definitively damaging exonic variants. We conclude that excess low-frequency variation, intragenic recombination and lack of common disruptive exonic variants favor complete resequencing as the optimal approach for genetic association studies to identify regulatory SFTPB variants that cause neonatal respiratory distress syndrome in genetically diverse populations.

Original languageEnglish (US)
Pages (from-to)170-175
Number of pages6
JournalPediatric research
Issue number2
StatePublished - Aug 2007

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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