Potential contribution of SIM2 and ETS2 functional polymorphisms in Down syndrome associated malignancies
Autor: | Chinmay Kumar Panda, Keya Chaudhuri, Nupur Mukherjee, Ananda L. Roy, Samikshan Dutta, Arpita Chatterjee, Avirup Dutta, Swagata Sinha, Kanchan Mukhopadhyay, Ashis Mukherjee, Sanjit Mukherjee |
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Jazyk: | angličtina |
Předmět: |
lcsh:Internal medicine
Linkage disequilibrium Down syndrome lcsh:QH426-470 ETS2 Population India Breast Neoplasms Biology Acute lymphoblastic leukemia Polymorphism Single Nucleotide Linkage Disequilibrium Proto-Oncogene Protein c-ets-2 Breast cancer Gene Frequency medicine Basic Helix-Loop-Helix Transcription Factors Genetics Humans Computer Simulation Genetics(clinical) Allele lcsh:RC31-1245 education SIM2 Allele frequency Genetics (clinical) Genetic association Mouth neoplasm education.field_of_study Oral cancer Haplotype Epistasis Genetic Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Pedigree lcsh:Genetics Haplotypes Case-Control Studies Female Mouth Neoplasms Research Article |
Zdroj: | BMC Medical Genetics BMC Medical Genetics, Vol 14, Iss 1, p 12 (2013) |
ISSN: | 1471-2350 |
DOI: | 10.1186/1471-2350-14-12 |
Popis: | Background Proper expression and functioning of transcription factors (TFs) are essential for regulation of different traits and thus could be crucial for the development of complex diseases. Subjects with Down syndrome (DS) have a higher incidence of acute lymphoblastic leukemia (ALL) while solid tumors, like breast cancer (BC) and oral cancer (OC), show rare incidences. Triplication of the human chromosome 21 in DS is associated with altered genetic dosage of different TFs. V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and Single Minded 2 (SIM2) are two such TFs that regulate several downstream genes involved in developmental and neurological pathways. Here we studied functional genetic polymorphisms (fSNP) in ETS2 and SIM2 encoding genes in a group of patients and control subjects to better understand association of these variants with DS phenotypes. Methods We employed an in silico approach to identify potential target pathways of ETS2 and SIM2. fSNPs in genes encoding for these two TFs were identified using available databases. Selected sites were genotyped in individuals with DS, their parents, ALL, BC, OC as well as ethnically matched control individuals. We further analyzed these data by population-based statistical methods. Results Allelic/genotypic association analysis showed significant (P Conclusions We infer from the present investigation that the difference in frequencies of fSNPs and their independent as well as interactive effects may be the cause for altered expression of SIM2 and ETS2 in DS and malignant groups, which affects different downstream biological pathways. Thus, altered expression of SIM2 and ETS2 could be one of the reasons for variable occurrence of different malignant conditions in DS. |
Databáze: | OpenAIRE |
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