Erik and Kacie to present at Student Seminar on Thursday (18.March) at noon in 2-501 BSB
Background for Erik’s talk
Telomere attrition is a natural process that occurs due to inadequate telomere maintenance during cell division or damaging agents such as reactive oxygen species (ROS). Once at a critically short threshold, telomeres signal the cell to senesce. Telomerase is capable of circumventing senescence by adding de novo telomere repeats to the ends of chromosomes. One disease caused by insufficient levels of telomerase and telomere dysfunction is Dyskeratosis Congenita (DC, OMIM). DC is a congenital bone marrow failure disorder characterized by the clinical triad of nail dystrophy, leukoplakia and skin dyspigmentation. We have previously uncovered defects related to DC in cell culture that include extremely short telomeres, a proliferation defect and early entry into senescence. These cells have now been further characterized and we have uncovered the mechanism by which the cell transduces short telomere signaling in order to engage early senesce. This signaling ultimately elevates ROS to slow cell proliferation and engage senescence. These findings have potential implications on therapeutic interventions for DC patients as well as a means by which telomeres drive aging.
Background for Kacie’s talk
Bardet-Biedl syndrome (BBS, OMIM) is an autosomal recessive and genetically heterogeneous disorder characterized by obesity, retinopathy, renal malformation, and hypogonadism. Although a rare disorder, BBS serves as a model to study these and other phenotypes that are individually common in the general population. Mutations in 12 different genes, BBS1-12, account for 63% of BBS; causative mutations have yet to be discovered in the remainder. In recent years genome-wide studies of CNVs have been highly successful in elucidating genetic risk factors for complex disease. In this study, we apply copy number detection technology to a simple Mendelian disorder in an effort to identify novel disease genes and to define a role for CNVs in BBS. 32 BBS patients from non-consanguineous families with unknown mutations were hybridized to the Affymetrix Genome-Wide Human SNP Array 5.0 and analyzed for copy number variants (CNVs) using a publicly available program, PennCNV. From the data set, 11 CNVs that were novel to the Database of Genomic Variants and absent from our control set of 500 individuals were classified as being high interest. We identified one patient hemizygous for BBS10 and detected a frame shift mutation in the remaining copy by direct sequencing. In addition, we identified a deletion of one exon in a promising candidate gene, which is predicted to cause a frame shift and premature stop of the protein. Zebrafish and cell-based model systems have provided additional insight into the effect of this CNV. Overall, this dataset has set a precedent for the interrogation of CNVs in individuals with Mendelian disorders.
Posted on March 15, 2010, in Student Seminar and tagged BBS, Copy number variation, Dyskeratosis Congenita, Erik W., Kacie M., reactive oxygen specieies, telomerase, telomere. Bookmark the permalink. Leave a comment.