Bioinformatics
Efforts by human genome project resulted in enormous amount of data related to genetic variation in humans. Our laboratory utilizes publicly available databases to extract detailed information on the genes of interest and their genetic variants. Currently we are targeting the major cancer related pathways including cell signaling, cell cycle, DNA repair, apoptosis, angiogenesis and immune system. The aim of this approach is to compile meaningful information regarding the genetic variants and to characterize their potential influence on the function and intrinsic properties of proteins. The influence of genetic variants on the function of individual proteins, protein complexes and biological pathways are investigated.

Molecular Applications

We have hypothesized that genetic anticipation occurs in some breast cancer families and that, as shown in other genetic diseases, it is the result of intergenerational instability of trinucleotide repeats in susceptibility genes. One of the current projects focuses on investigating novel high-risk breast cancer genes that undergo trinucleotide repeat expansion in breast cancer. We have shown that a fraction of breast cancer cases are associated with large, expanded trinucleotide repeats. These expansions may influence the function or the intrinsic properties of nearby gene(s). We are in the progress of cloning the genes associated with repeat expansions using a repeat based cloning strategy. . This will help us understand the influence of trinucleotide repeat expansions on the normal function of the identified gene(s) and understand their contribution to breast cancer. Our proposed approach has the potential to allow the rapid identification of novel breast cancer predisposition gene(s), which will provide benefits for women with breast cancer. Identification of genes with unstable repeat expansions will open new avenues in the study of the molecular genetics of breast cancer.

Genes of interest are further investigated for the presence of novel variants using mutational pre-screening methods such as SSCP, ARMS and Enzymatic Digestion. Automated Sequencing is applied to further characterize the exact nature of genetic variants detected by pre-screening methods. These methods are also utilized to validate the presence of genetic variants identified using public databases, as well as to estimate their allelic frequencies in our populations.