Yazar, Ömer Faruk
Many unsolved rare diseases lack etiological information at the molecular level. In many cases mode of inheritance is may not be identified correctly, and even if a variant is identified, new functional studies are required to establish genotype-phenotype associations. Factors hamper rare disease research, such as the low number of patients, the absence of biomarkers, and the lack of effective diagnostics. The need for a joint effort between clinicians and researchers has been increasing. Enhancements in bioinformatics algorithms, new literature, and published cases in databases enable rare disease research to reveal new variants through manual curation or automated data mining. Reanalysis of exome sequencing data for unsolved rare disease cases has the potential to reveal novel gene and disease associations due to recent developments in bioinformatics tools. Additionally, recent technological advancements in sequencing technologies have increased the quality of raw exome data, increasing the success rate for variant discovery. Here, we present the importance of reanalyzing older sequencing data with recent algorithms and literature as well as resequencing DNA samples with the latest instruments for challenging rare diseases in a case study.


Inference of the stochastic MAPK pathway by modified diffusion bridge method
Purutçuoğlu Gazi, Vilda (2013-03-01)
The MAPK pathway is one of the well-known systems in oncogene researches of eukaryotes due to its important role in cell life. In this study, we perform the parameter estimation of a realistic MAPK system by using western blotting data. In inference, we use the modified diffusion bridge algorithm with data augmentation technique by modelling the realistically complex system via the Euler-Maruyama approximation. This approximation, which is the discretized version of the diffusion model, can be seen as an al...
Selection of representative SNP sets for genome-wide association studies: a metaheuristic approach
Ustunkar, Gurkan; AKYÜZ, SÜREYYA; Weber, Gerhard W.; Friedrich, Christoph M.; Aydın Son, Yeşim (2012-08-01)
After the completion of Human Genome Project in 2003, it is now possible to associate genetic variations in the human genome with common and complex diseases. The current challenge now is to utilize the genomic data efficiently and to develop tools to improve our understanding of etiology of complex diseases. Many of the algorithms needed to deal with this task were originally developed in management science and operations research (OR). One application is to select a subset of the Single Nucleotide Polymor...
Impacts of multistressors on the survival and life history traits of Daphnia Pulex
Bezirci, Gizem; Beklioğlu, Meryem; Department of Biology (2008)
As Daphnia have an important role in freshwater food webs, it is important to understand how environmental stressors affect their survival and life history traits. Daphnia pulex were first acutely exposed to a combination of NaCl salinities (0.00-10.0 g/L) and fish-exuded kairomone. The 24 and 48 hour LC50 values were 0.401 and 0.159 g/L in kairomone-absence and 1.962 and 1.007 g/L in kairomone-presence. Hence, survival decreased with increasing salinity, while the kairomone enhanced daphnid resistance to s...
Potential role of phosphatidylinositol 3 kinase, rather than DNA-dependent protein kinase, in CpG DNA-induced immune activation.
Ishii, KJ; Takeshita, F; Gursel, I; Gürsel, Mayda; Conover, J; Nussenzweig, A; Klinman, DM (Rockefeller University Press, 2002-07-15)
Unmethylated CpG motifs present in bacterial DNA stimulate a strong innate immune response. There is evidence that DNA-dependent protein kinase (DNA-PK) mediates CpG signaling. Specifically, wortmannin (an inhibitor of phosphatidylinositol 3 kinase [PI3]-kinases including DNA-PK) interferes with CpG-dependent cell activation, and DNA-PK knockout (KO) mice fail to respond to CpG stimulation. Current studies establish that wortmannin actually inhibits the uptake and colocalization of CpG DNA with toll-like re...
Biophysical investigation of the effects of antioxidants on normal and diabetic rat bone tissues at molecular level
Boyar, Handan; Severcan, Feride; Department of Biology (2004)
In the first part of this study, the effect of diabetes mellitus on the long bones (femur and tibia) of the streptozocin induced diabetic rats and the effect of selenium (Se) treatment on these bones are investigated at molecular level by Fourier transform infrared (FTIR) spectroscopy, light and electron microscopy. In the second part of this study, the effect of selenium and vitamin E deficiency or selenium toxicity on rat bones have been studied by FTIR spectroscopy. The results of the first part of the p...
Citation Formats
Ö. F. Yazar, “UTILITY OF RESEQUENCING AND REANALYSIS FOR UNSOLVED RARE DISEASES,” M.S. - Master of Science, Middle East Technical University, 2022.