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Thiazolidinedione (TZD) insulin sensitizers have the potential to effectively treat a number of human diseases, however the currently available agents have dose-limiting side effects that are mediated via activation of the transcription factor PPARγ. We have recently shown PPARγ-independent actions of TZD insulin sensitizers, but the molecular target of(More)
OBJECTIVE While multiple lines of evidence suggest the importance of genetic contributors to risk of preterm birth, the nature of the genetic component has not been identified. We perform segregation analyses to identify the best fitting genetic model for gestational age, a quantitative proxy for preterm birth. METHODS Because either mother or infant can(More)
To determine the population-based frequency of a rare mutation (the 121ins2 mutation in the surfactant protein B gene), we developed high-throughput techniques to extract reliably and rapidly amplifiable DNA from Guthrie cards. Using a 3-mm punch from each of 10,044 Guthrie cards obtained from the Missouri Department of Health, we extracted DNA with(More)
Four collections of human X-specific YACs, derived from human cells containing supernumerary X chromosomes or from somatic cell hybrids containing only X human DNA were characterized. In each collection, 80-85% of YAC strains contained a single X YAC. Five thousand YACs from the various libraries were sized, and cocloning was assessed in subsets by the(More)
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(More)
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,(More)
Genetic variants in intron 4 of the surfactant protein B gene SFTPB have been associated with pulmonary morbidity in newborn infants and adults. Genetic variant discovery in intron 4 requires high fidelity polymerase amplification due to a variable number of intermotif dinucleotide repeats and reliable characterization of alleles genetically distinct due to(More)
OBJECTIVE Surfactant protein B deficiency is a lethal cause of respiratory distress in infancy that results most commonly from a homozygous frameshift mutation (121ins2). Using independent clinical ascertainment and molecular methods in different populations, we sought to determine allele frequency. STUDY DESIGN Using clinical characteristics of the(More)
BACKGROUND Genetic and developmental disruption of surfactant protein B (SP-B) expression causes neonatal respiratory distress syndrome (RDS). OBJECTIVES To assess developmental and genetic regulation of SP-B expression in vivo. METHODS To evaluate in vivo developmental regulation of SP-B, we used immunoblotting to compare frequency of detection of(More)
BACKGROUND Rapid technological advances in genetic research and public concern about genetic discrimination have led to anticipatory safeguards in the informed consent process in the absence of legal examples of proven discrimination. Despite federal and state regulations to restrict access to personal health information, including genetic information,(More)