Jennifer A Wambach1, Daniel J Wegner2, Hillary B Heins2, Todd E Druley3, Robi D Mitra4, Aaron Hamvas2, F Sessions Cole2. 1. Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO. Electronic address: wambach_j@kids.wustl.edu. 2. Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO. 3. Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO; Center for Genome Sciences and Systems Biology, Department of Genetics, Washington University School of Medicine, St. Louis, MO. 4. Center for Genome Sciences and Systems Biology, Department of Genetics, Washington University School of Medicine, St. Louis, MO.
Abstract
OBJECTIVE: To determine whether synonymous variants in the adenosine triphosphate-binding cassette A3 transporter (ABCA3) gene increase the risk for neonatal respiratory distress syndrome (RDS) in term and late preterm infants of European and African descent. STUDY DESIGN: Using next-generation pooled sequencing of race-stratified DNA samples from infants of European and African descent at ≥34 weeks gestation with and without RDS (n = 503), we scanned all exons of ABCA3, validated each synonymous variant with an independent genotyping platform, and evaluated race-stratified disease risk associated with common synonymous variants and collapsed frequencies of rare synonymous variants. RESULTS: The synonymous ABCA3 variant frequency spectrum differs between infants of European descent and those of African descent. Using in silico prediction programs and statistical strategies, we found no potentially disruptive synonymous ABCA3 variants or evidence of selection pressure. Individual common synonymous variants and collapsed frequencies of rare synonymous variants did not increase disease risk in term and late-preterm infants of European or African descent. CONCLUSION: In contrast to rare, nonsynonymous ABCA3 mutations, synonymous ABCA3 variants do not increase the risk for neonatal RDS among term and late-preterm infants of European or African descent.
OBJECTIVE: To determine whether synonymous variants in the adenosine triphosphate-binding cassette A3 transporter (ABCA3) gene increase the risk for neonatal respiratory distress syndrome (RDS) in term and late preterm infants of European and African descent. STUDY DESIGN: Using next-generation pooled sequencing of race-stratified DNA samples from infants of European and African descent at ≥34 weeks gestation with and without RDS (n = 503), we scanned all exons of ABCA3, validated each synonymous variant with an independent genotyping platform, and evaluated race-stratified disease risk associated with common synonymous variants and collapsed frequencies of rare synonymous variants. RESULTS: The synonymous ABCA3 variant frequency spectrum differs between infants of European descent and those of African descent. Using in silico prediction programs and statistical strategies, we found no potentially disruptive synonymous ABCA3 variants or evidence of selection pressure. Individual common synonymous variants and collapsed frequencies of rare synonymous variants did not increase disease risk in term and late-preterm infants of European or African descent. CONCLUSION: In contrast to rare, nonsynonymous ABCA3 mutations, synonymous ABCA3 variants do not increase the risk for neonatal RDS among term and late-preterm infants of European or African descent.
Authors: Frank Brasch; Sven Schimanski; Christian Mühlfeld; Stefan Barlage; Thomas Langmann; Charalampos Aslanidis; Alfred Boettcher; Ashraf Dada; Horst Schroten; Eva Mildenberger; Eric Prueter; Manfred Ballmann; Matthias Ochs; Georg Johnen; Matthias Griese; Gerd Schmitz Journal: Am J Respir Crit Care Med Date: 2006-05-25 Impact factor: 21.405
Authors: Chava Kimchi-Sarfaty; Jung Mi Oh; In-Wha Kim; Zuben E Sauna; Anna Maria Calcagno; Suresh V Ambudkar; Michael M Gottesman Journal: Science Date: 2006-12-21 Impact factor: 47.728
Authors: Jennifer A Wambach; Ping Yang; Daniel J Wegner; Hillary B Heins; Lyudmila N Kaliberova; Sergey A Kaliberov; David T Curiel; Frances V White; Aaron Hamvas; Brian P Hackett; F Sessions Cole Journal: Am J Respir Cell Mol Biol Date: 2016-11 Impact factor: 6.914
Authors: Zoltán N Oltvai; Eric A Smith; Katie Wiens; Lawrence M Nogee; Mark Luquette; Andrew C Nelson; Kathryn A Wikenheiser-Brokamp Journal: Cold Spring Harb Mol Case Stud Date: 2020-06-12