Grantee Research Project Results
2001 Progress Report: Gene-Environment Interaction and Human Malformations
EPA Grant Number: R828292Title: Gene-Environment Interaction and Human Malformations
Investigators: Shaw, Gary M. , Finnell, Richard H. , Lammer, Edward J. , Carmichael, Suzan L. , Torfs, Claudine P.
Current Investigators: Shaw, Gary M. , Loffredo, Christopher A. , Finnell, Richard H. , Lammer, Edward J. , Carmichael, Suzan L. , Torfs, Claudine P.
Institution: California Birth Defects Monitoring Program
Current Institution: California Birth Defects Monitoring Program , Children’s Hospital Oakland Research Institute , Georgetown University , Public Health Institute , Texas A & M University
EPA Project Officer: Aja, Hayley
Project Period: July 1, 2000 through June 30, 2005 (Extended to September 30, 2006)
Project Period Covered by this Report: July 1, 2000 through June 30, 2001
Project Amount: $3,373,557
RFA: Genetic Susceptibility and Variability of Human Malformations (1999) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
The goal of our research program is to determine whether an association exists between gene variants and specific exposures in their contribution to selected congenital anomalies. The specific aims are: 1) to analyze if genetic variations in infant and maternal genes involved in biotransformation and detoxification modify risks of malformations, in the presence or absence of selected maternal exposures to toxicants; 2) to analyze if genetic variations in infant or maternal folate-pathway genes modify risks of malformations, in the presence of variations in maternal folate intakes; and 3) to analyze if genetic variations in infant genes associated with vascular development and function modify risks of malformations, in the presence or absence of maternal exposures to vasoactive chemicals. The case-control research design includes 5000 cases and controls and focuses on these malformations: neural tube defects, selected heart malformations, orofacial clefts, limb defects, gastroschisis, and intestinal atresias. The analytic plan will combine maternal interview data with multiplex polymerase chain reaction-based genotyping for over 40 candidate genes on over 7200 samples.Progress Summary:
Progress on major project milestones is consistent with our projections that will ensure a successful completion of the project. In this initial year of funding, our focus has included the following activities and accomplishments: 1) We have received institutional review board approval. 2) We have established contracts, including scopes of work, with all collaborating institutions. 3) We have developed an electronic tracking system that monitors the status of all DNA source samples being used in this research program. 4) We have developed a detailed plan for the prioritization and procurement of DNA samples for genotyping as well as when analyses will be performed. 5) We have procured all existing samples that will be used in our genotyping experiments. Additional DNA samples from ongoing epidemiologic studies that are part of this research program are being collected on schedule and are being stored frozen. 6) From the perspective of laboratory activities, our focus has been on the development of multiplex PCR-based genotyping methods, particularly PCR-based multiplex panels of variants of drug-metabolizing enzymes. We have developed new methods for multiplex genotyping for N-acetyltransferases 1 & 2 (NAT1 and NAT2), glutathione-S-transferases M1 and T1, and CYP2D6. We have been working closely with scientists from Roche Molecular Systems on the multilocus genotyping assay Cardiovascular panel B (detects 32 polymorphisms from 23 candidate genes). This assay has now been successfully performed on 100 subjects. 7) At the time that this grant proposal was funded, MALDI-TOF mass spectrometry systems were not yet commercially available. We have submitted a NCRR Shared Instrumentation grant proposal to NIH requesting funds to purchase a MALDI-TOF mass spectrometer. We feel that this genotyping system would provide a superior approach to typing large numbers of SNPs for the large number of specimens in our research program.Future Activities:
Our major focus in the next reporting period will be to genotype hundreds of samples for biotransformation enzyme gene variants as well as genes available on the Cardiovascular Panel B. This genotype information will be incorporated into epidemiologic analyses to identify potential risk factors for selected congenital anomalies.Journal Articles:
No journal articles submitted with this report: View all 55 publications for this projectSupplemental Keywords:
health effects; exposure; teratogen; metabolism; genetic predisposition; genetic polymorphisms; susceptibility; chemicals; diet; epidemiology; genetics; measurement methods; western;region 9; California., RFA, Health, Scientific Discipline, Genetics, Health Risk Assessment, Epidemiology, Susceptibility/Sensitive Population/Genetic Susceptibility, Children's Health, genetic susceptability, Biology, health effects, risk assessment, sensitive populations, vulnerability, health risks, gene-environment interaction, exposure, human malformation, polymerase chain reaction, children, etiology, children's vulnerablity, toxicity, genotyping, biotransformation, dietary exposure, growth & development, pregnancy, developmental disorders, genetic susceptibility, maternal exposure, vascular development, environmental hazard exposuresProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- Final Report
- 2006
- 2005 Progress Report
- 2004 Progress Report
- 2003 Progress Report
- 2002 Progress Report
- Original Abstract
41 journal articles for this project