Proposed is a cross disciplinary training and research program designed to utilize and complement the background of the candidate by building the necessary components for a successful genome research career. Under the guidance of the advisors, the training and research plans will provide the candidate with an ideal background to contribute toward the realization of the goals of the Human Genome Project. The training aspect of this award is an in-depth study of contemporary molecular genetics and enzymology through formal coursework. In addition, the candidate will rotate through the various laboratories in the Institute for Molecular Genetics at Baylor College of Medicine. During this phase, the candidate will interact with scientists to develop an understanding of current laboratory techniques. Furthermore, local research lectures and national research conferences will be attended. Three research projects will be conducted during this award. The goal of the first project is to develop a technique which can determine semiquantitatively the number of tandemly repeated triplets in a given DNA sequence. This project will be applied to the diagnosis of myotonic dystrophy. It is proposed that an increase in the length of the tandemly repeated element increases the rate of hybridization due to an increase in the number of binding sites available for nucleation. An oligonucleotide array approach will be utilized in this study, and if successful, will demonstrate that this type of an approach can be applied to sequence analysis of DNA which contains repeated elements. The second project is an oligonucleotide array approach to genome mapping, in which an array of repeat elements are used to fingerprint an unknown DNA sequence. Finally, mutation detection chips, which can also determine sequence information, will be developed. These three projects will provide feasibility studies to evaluate oligonucleotide array approaches to both genome mapping and sequence analysis.
| Shumaker, J M; Metspalu, A; Caskey, C T (1996) Mutation detection by solid phase primer extension. Hum Mutat 7:346-54 |
