Intracellular calcium concentration ([Ca 2+ ] i) may have an important role in the development of chemoresistance, which is an essential problem in cancer chemotherapy. Cisplatin (DDP), which modulates the intracellular calcium concentration by different mechanisms, is an antineoplastic agent with high success rate in cancer therapies. We investigated the regulatory role of [Ca 2+ ] in cisplatin resistance in epithelial ovarian cancer cell line, in MDAH-2774, and its chemoresistant subclone MDAH-2774/DDP. The measurement of [Ca 2+ ] i using fluorescence microscope, and flow cytometry revealed that the amount of intracellular calcium decreased in cisplatin resistant cells compared to the amounts in parental cells. mRNA expression profiles of calcium homeostasisassociated major genes (IP 3 R1/2/3, RYR1/2, SERCA1/2/3, NCX1/2/3, PMCA1/2/3, and PMCA4) decreased in cisplatin resistant cell line in comparison to the expression profiles in parental cells. Owing to the changes in the expression of genes involved in calcium regulation, these results show, drug resistance may be prevented by introducing a new perspective on the use of inhibitors and activators of these genes, and thus of cytostatic treatment strategies, due to changes in the expression of genes involved in calcium regulation.

No abstract

No abstract

<b><i>Background:</i></b> In the context of medical genetics, gene hunting is the process of identifying and functionally characterizing genes or genetic variations that contribute to disease phenotypes. In this review, we would like to summarize gene hunting process in terms of historical aspects from Darwin to now. For this purpose, different approaches and recent developments will be detailed. <b><i>Summary:</i></b> Linkage analysis and association studies are the most common methods in use for explaining the genetic background of hereditary diseases and disorders. Although linkage analysis is a relatively old approach, it is still a powerful method to detect disease-causing rare variants using family-based data, particularly for consanguineous marriages. As is known that, consanguineous marriages or endogamy poses a social problem in developing countries, however, this same condition also provides a unique opportunity for scientists to identify and characterize pathogenic variants. The rapid advancements in sequencing technologies and their parallel implementation together with linkage analyses now allow us to identify the candidate variants related to diseases in a relatively short time. Furthermore, we can now go one step further and functionally characterize the causative variant through in vitro and in vivo studies and unveil the variant-phenotype relationships on a molecular level more robustly. <b><i>Key Messages:</i></b> Herein, we suggest that the combined analysis of linkage and exome analysis is a powerful and precise tool to diagnose clinically rare and recessively inherited conditions.