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. Copyright 2008 Wiley-Liss, Inc.
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 121ins2SFTPB 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. Copyright 2008 Wiley-Liss, Inc.
Authors: F S Cole; A Hamvas; P Rubinstein; E King; M Trusgnich; L M Nogee; D E deMello; H R Colten Journal: Pediatrics Date: 2000-03 Impact factor: 7.124
Authors: K Ardlie; S N Liu-Cordero; M A Eberle; M Daly; J Barrett; E Winchester; E S Lander; L Kruglyak Journal: Am J Hum Genet Date: 2001-07-25 Impact factor: 11.025
Authors: Alan Q Thomas; Kirk Lane; John Phillips; Melissa Prince; Cheryl Markin; Marcy Speer; David A Schwartz; Radhika Gaddipati; Annis Marney; Joyce Johnson; Richard Roberts; Jonathan Haines; Mildred Stahlman; James E Loyd Journal: Am J Respir Crit Care Med Date: 2002-05-01 Impact factor: 21.405
Authors: 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 Journal: Pediatr Res Date: 2007-08 Impact factor: 3.756
Authors: Jennifer A Wambach; Ping Yang; Daniel J Wegner; Ping An; Brian P Hackett; F S Cole; Aaron Hamvas Journal: Pediatr Res Date: 2010-09 Impact factor: 3.756
Authors: Geoffrey Kurland; Robin R Deterding; James S Hagood; Lisa R Young; Alan S Brody; Robert G Castile; Sharon Dell; Leland L Fan; Aaron Hamvas; Bettina C Hilman; Claire Langston; Lawrence M Nogee; Gregory J Redding Journal: Am J Respir Crit Care Med Date: 2013-08-01 Impact factor: 21.405