Exome sequencing of family trios from the National Birth Defects Prevention Study: Tapping into a rich resource of genetic and environmental data

Mary M Jenkins; Lynn M Almli; Faith Pangilinan; Jessica X Chong; Elizabeth E Blue; Stuart K Shapira; Janson White; Daniel McGoldrick; Joshua D Smith; James C Mullikin; Christopher J Bean; Wendy N Nembhard; Xiang-Yang Lou; Gary M Shaw; Paul A Romitti; Kim Keppler-Noreuil; Mahsa M Yazdy; Denise M Kay; Tonia C Carter; Andrew F Olshan; Kristin J Moore; Nanette Nascone-Yoder; Richard H Finnell; Philip J Lupo; Marcia L Feldkamp; NISC Comparative Sequencing Program; University of Washington Center for Mendelian Genomics; Deborah A Nickerson; Michael J Bamshad; Lawrence C Brody; Jennita Reefhuis; National Birth Defects Prevention Study

doi:10.1002/bdr2.1554

Exome sequencing of family trios from the National Birth Defects Prevention Study: Tapping into a rich resource of genetic and environmental data

Birth Defects Res. 2019 Dec 1;111(20):1618-1632. doi: 10.1002/bdr2.1554. Epub 2019 Jul 21.

Authors

Mary M Jenkins¹, Lynn M Almli^{1

2}, Faith Pangilinan³, Jessica X Chong⁴, Elizabeth E Blue⁵, Stuart K Shapira¹, Janson White⁴, Daniel McGoldrick⁶, Joshua D Smith⁶, James C Mullikin³, Christopher J Bean¹, Wendy N Nembhard⁷, Xiang-Yang Lou⁸, Gary M Shaw⁹, Paul A Romitti¹⁰, Kim Keppler-Noreuil¹¹, Mahsa M Yazdy¹², Denise M Kay¹³, Tonia C Carter¹⁴, Andrew F Olshan¹⁵, Kristin J Moore¹⁵, Nanette Nascone-Yoder¹⁶, Richard H Finnell¹⁷, Philip J Lupo¹⁸, Marcia L Feldkamp¹⁹; NISC Comparative Sequencing Program²⁰; University of Washington Center for Mendelian Genomics²¹; Deborah A Nickerson⁶, Michael J Bamshad^{4

6}, Lawrence C Brody³, Jennita Reefhuis¹; National Birth Defects Prevention Study

Affiliations

¹ National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia.
² Carter Consulting Incorporated, Atlanta, Georgia.
³ National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
⁴ Department of Pediatrics, University of Washington, Seattle, Washington.
⁵ Department of Medicine, University of Washington, Seattle, Washington.
⁶ Department of Genome Sciences, University of Washington, Seattle, Washington.
⁷ Fay W Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
⁸ College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
⁹ Stanford University School of Medicine, Department of Pediatrics, Stanford, California.
¹⁰ Department of Epidemiology, University of Iowa, Iowa City, Iowa.
¹¹ Children's National Medical Center, George Washington University, Washington, District of Columbia.
¹² Massachusetts Department of Public Health, Boston, Massachusetts.
¹³ Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York.
¹⁴ Marshfield Clinic Research Institute, Marshfield, Wisconsin.
¹⁵ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina.
¹⁶ Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.
¹⁷ Center for Precision Environmental Health, Departments of Molecular & Cellular Biology and Medicine, Baylor College of Medicine, Houston, Texas.
¹⁸ Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas.
¹⁹ Division of Medical Genetics, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah.
²⁰ NIH Intramural Sequencing Center, National Human Genome Research Institute, Bethesda, Maryland.
²¹ University of Washington, Seattle, Washington.

Abstract

Background: The National Birth Defects Prevention Study (NBDPS) is a multisite, population-based, case-control study of genetic and nongenetic risk factors for major structural birth defects. Eligible women had a pregnancy affected by a birth defect or a liveborn child without a birth defect between 1997 and 2011. They were invited to complete a telephone interview to collect pregnancy exposure data and were mailed buccal cell collection kits to collect specimens from themselves, their child (if living), and their child's father. Over 23,000 families representing more than 30 major structural birth defects provided DNA specimens.

Methods: To evaluate their utility for exome sequencing (ES), specimens from 20 children with colonic atresia were studied. Evaluations were conducted on specimens collected using cytobrushes stored and transported in open versus closed packaging, on native genomic DNA (gDNA) versus whole genome amplified (WGA) products and on a library preparation protocol adapted to low amounts of DNA.

Results: The DNA extracted from brushes in open packaging yielded higher quality sequence data than DNA from brushes in closed packaging. Quality metrics of sequenced gDNA were consistently higher than metrics from corresponding WGA products and were consistently high when using a low input protocol.

Conclusions: This proof-of-principle study established conditions under which ES can be applied to NBDPS specimens. Successful sequencing of exomes from well-characterized NBDPS families indicated that this unique collection can be used to investigate the roles of genetic variation and gene-environment interaction effects in birth defect etiologies, providing a valuable resource for birth defect researchers.

Keywords: birth defects; gene-environment interaction; genetics; intestinal atresia; sequence analysis.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Congenital Abnormalities / genetics*
Congenital Abnormalities / prevention & control*
Exome Sequencing*
Family
Gene-Environment Interaction*
Humans

Abstract

Publication types

MeSH terms

Grants and funding