Identification of polymorphisms and mutations in the DNA sequence of patients deficient in DNA repair processes

Abstract

Although highly stable, DNA molecule undergoes thousands of changes in its genetic code every day, due to spontaneous exposure to various mutagens. Most of these changes are readily removed by a number of DNA repair processes. The process of nucleotide excision repair (NER) is the most versatile and flexible dealing with a variety of lesions that can lead to distortions of the DNA helices. Among the several agents that damage DNA, inducing substrates for the NER pathway, there is ultraviolet (UV) light, subdivided into UVC (220-280 nm), UVB (280-315 nm) and UVA (315 - 400 nm). The longer the wavelength UV lights (UVB and UVA) reach the earth surface and are capable of crossing layers of the human skin tissue and causing damage to the DNA molecule. These DNA damage, if not repaired, can generate mutations causing diseases, including cancer and aging. Some syndromes, sensitive to sunlight, are related to deficiencies in the NER process, such as Xeroderma Pigmentosum (XP), Cockayne syndrome (CS) and Trichothiodystrophy (TTD). Our research group is highly interested in those syndromes and in this project, we propose the in silico identification of mutations and polymorphisms found in genes related to DNA repair process, from Brazilian XP patients samples, after DNA sequencing by next generation sequencing equipment (ABI 5500XL SOLiD) and dedicated next-generation Bioinformatics softwares. Furthermore, we aim to develop a user friendly platform to search nucleotide substitutions responsible for the symptoms in these patients. Thus, we plan to create a public domain interface that will facilitate the identification of substitutions / polymorphisms in data generated by the SOLiD sequencing platform.