This is a revision of Program Project proposal 1 PO1 HD-047609 'Gene-Environment Interactions inHuman Parturition' that was submitted in October 2003, reviewed by an NICHD Special Emphasis Panel, andreceived a priority score of 199 (30th percentile). In this research program we proposed to identify thegenetic and environmental determinants of the length of human gestation/ timing of onset of spontaneousparturition, and to model the gene, environment, and maternal-fetal interactions that may underlie the risk ofpremature birth among three racial/ ethnic populations: African-Americans, Hispanics and nonHispanicWhites.The previous review commented very favorably on all aspects of the Genotyping Core as proposed,and noted that the expertise of the Core Director (Hixson) and track record of gene sequencing efforts atthe University of Texas Human Genetics Center would ensure the goals will be realized and the reliability ofthe results will be at the highest possible level. The review did not raise any concerns. The Core received apriority score of 110.One issue that was brought up in the review of Project III relates to the accuracy of the MALDI-TOFplatform for SNP assay in a high throughput environment. Since this issue is pertinent to the Genotyping Core,it is addressed here in the present revision with the following data about assay reliability that was generatedby the Core.'Mefhodo/ogy for re-sequencing and SNP typing are not fully established in Core C and Project 1 onwhich Project 3 depends - accuracy of the allele calls with the MALDI-TOF platform of SNP assay is still notfully documented in a high throughput environment.'Many different automated platforms have been developed for high-throughput genotyping basedon a wide array of current molecular technologies. The BruckerBiflex III MALDI-TOF system (Sequenom, Inc.) is a proven and wellestablishedgenotyping platform that is based on distinguishingallele-specific mini-sequencing reactions using mass spectrometryanalysis. In our hands, we have found that the Sequenom platformproduces accurate and consistent allele calls in a high-throughputenvironment. We have used this instrument for several largeepidemiological studies that included comprehensive blindduplicate programs to assess genotyping error rates. The numbers ofblind duplicates in these studies range from 5% to 10% of thesamples. Table 1 presents results from a monthly survey of blindduplicate data for an on-going study. This analysis of seven differentpolymorphisms (A-G) yielded 98-100% agreement for blind duplicateallele calls. This information is now included in the revised descriptionof the Core (p.304).
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