GENOTYPING PERFORMANCE OF DNA FROM STORED SERUM: A PILOT STUDY IN THE COLLABORATIVE PERINATAL PROJECT

University Of Minnesota, Minneapolis MN

Investigators

Abstract

Large scale genetic epidemiology studies are valuable to discover genetic risks to perinatal outcomes and to investigate gene-environment interactions in complex phenotypes. Availability of genome-wide data from well characterized cohorts opens new platforms to test several hypotheses and detect molecular mechanisms of adverse perinatal outcomes. However, some well-designed and phenotypically characterized perinatal epidemiology cohorts established before genomics was integrated into large scale epidemiological studies may not have stored buffy coat or whole blood samples that are known to yield high quality DNA for high throughput genotyping. Some of these well-designed cohorts have banked serum for a large number of participants, making them very attractive for large-scale genetic epidemiology studies provided adequate and good quality DNA can be obtained. One such prospective cohort is the Collaborative Perinatal Project (CPP). The CPP is a national birth cohort that enrolled pregnant women who presented for prenatal care at 12 US university hospital clinics between 1959 and 1966, and followed their offspring through age 7 years. Approximately 60,000 pregnancies of 48,000 women (46% White, 46.2% Black, 6.8% Puerto Rican, 1% others) and 59,000 children born to those women were enrolled [1]. Clinical and interview data are available on maternal conditions, obstetric complications and interventions, and offspring growth and developmental traits. Blood samples were collected for the vast majority of study participants, and sera isolated from blood samples of women, cord blood of newborns, and whole blood of selected offspring obtained at their 4 month pediatric examination are stored at -20°C. The CPP serum bank is administered by the Division of Intramural Population Health Research (DIPHR) within the National Institute of Child Health and Human Development (NICHD). Provided usable amount and quality of DNA can be purified from the stored CPP sera, the available biobank data offers a new platform to test several biomedical research hypotheses. Specifically, the CPP offers unique opportunities to study genetic, evolutionary, maternal-fetal gene interactions, and gene-environment influences on gestational timing, fetal growth, health disparities, and neurodevelopmental disorders. Strengths of the CPP for such approaches include the hypothesis-free design of the study, the large number of good quality clinical and interview data, ethnic diversity of the samples, and availability of stored serum for a large number of subjects. In addition, the offspring for whom clinical data and biospecimens were collected at birth are now in their mid-50?s, and may be recruited to participate in future studies that aim to test several hypotheses to understand genetic mechanisms in the links between early growth/development and adult onset diseases including cardiometabolic disorders and mortality. Therefore, this task order aims to extract DNA from CPP serum samples stored for more than 50 years, restore damaged DNA, and evaluate genotyping performance in both genome-wide microarrays and real-time quantitative PCR assays.