|Title||Exome sequencing of family trios from the National Birth Defects Prevention Study: Tapping into a rich resource of genetic and environmental data.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Jenkins, MM, Almli, LM, Pangilinan, F, Chong, JX, Blue, EE, Shapira, SK, White, J, McGoldrick, D, Smith, JD, Mullikin, JC, Bean, CJ, Nembhard, WN, Lou, X-Y, Shaw, GM, Romitti, PA, Keppler-Noreuil, K, Yazdy, MM, Kay, DM, Carter, TC, Olshan, AF, Moore, KJ, Nascone-Yoder, N, Finnell, RH, Lupo, PJ, Feldkamp, ML, Nickerson, DA, Bamshad, MJ, Brody, LC, Reefhuis, J|
|Corporate Authors||NISC Comparative Sequencing Program, University of Washington Center for Mendelian Genomics, National Birth Defects Prevention Study|
|Journal||Birth Defects Res|
|Date Published||2019 Dec 01|
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.
|Alternate Journal||Birth Defects Res|
|PubMed Central ID||PMC6889076|
|Grant List|| / HL / NHLBI NIH HHS / United States |
NOFO DD18-001 / CC / CDC HHS / United States
PA 02081 / CC / CDC HHS / United States
FOA DD13-003 / CC / CDC HHS / United States
U01 DD001035 / DD / NCBDD CDC HHS / United States
CC999999 / IC / Intramural CDC HHS / United States
/ / NIH's Division of Intramural Research of the NHGRI /
UM1 HG006493 / HG / NHGRI NIH HHS / United States
PA 96043 / CC / CDC HHS / United States
FOA DD09-001 / CC / CDC HHS / United States
U24 HG008956 / HG / NHGRI NIH HHS / United States