Browsing by Subject "genes"
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Item Molecular Mechanisms of High-Altitude Acclimatization(MDPI, 2023-01-22) Mallet, Robert T.; Burtscher, Johannes; Pialoux, Vincent; Pasha, Qadar; Ahmad, Yasmin; Millet, Gregoire P.; Burtscher, MartinHigh-altitude illnesses (HAIs) result from acute exposure to high altitude/hypoxia. Numerous molecular mechanisms affect appropriate acclimatization to hypobaric and/or normobaric hypoxia and curtail the development of HAIs. The understanding of these mechanisms is essential to optimize hypoxic acclimatization for efficient prophylaxis and treatment of HAIs. This review aims to link outcomes of molecular mechanisms to either adverse effects of acute high-altitude/hypoxia exposure or the developing tolerance with acclimatization. After summarizing systemic physiological responses to acute high-altitude exposure, the associated acclimatization, and the epidemiology and pathophysiology of various HAIs, the article focuses on molecular adjustments and maladjustments during acute exposure and acclimatization to high altitude/hypoxia. Pivotal modifying mechanisms include molecular responses orchestrated by transcription factors, most notably hypoxia inducible factors, and reciprocal effects on mitochondrial functions and REDOX homeostasis. In addition, discussed are genetic factors and the resultant proteomic profiles determining these hypoxia-modifying mechanisms culminating in successful high-altitude acclimatization. Lastly, the article discusses practical considerations related to the molecular aspects of acclimatization and altitude training strategies.Item Obesity Genetics: The Prevalence of DRD2, DAT1 and DBH Genes in the Obese Individual(1998-08-01) Davis, Karla R.; Eisenberg, Arthur; Agarwal, Neeraj; Sherman, MarkDavis, Karla R., Obesity Genetics: The prevalence of DRD2, DAT1 and DBH Genes in the obese individual. Master of Science (Biomedical Sciences), August, 1998, 106 pp., 3 tables, 14 illustrations, reference, 44 titles. Obesity has been presented in research literature as a polygenic or multiple gene disorder. Currently, 3 genes have been associated with obesity, dopamine receptor D2 (DRD2), dopamine transporter (DAT1), and dopamine beta hydroxylase (DBH). The primary objective of this study is to analyze the DRD2, DAT1 and DBH genes to determine if a correlation exists between certain allelic variations of these 3 genes and the body mass index of obese individuals. We have developed an assay for the DRD2, DAT1 and DBH genes, utilizing polymerase chain reaction (PCR) technology. Within the DRD2 gene, 2 allelic variants have been identified, the A1 and A2 alleles. The A1 allele consists of a 310 bp fragment in which the Taq 1 restriction site has been deleted. The A2 allele consists of 180 bp fragment and a 130 bp fragment. The presence of the A1 allele after enzyme digestion has shown a strong correlation to obesity in prior studies. With respect to the DAT1 gene, a VNTR of 40 bp’s has been correlated to other disorders within the ‘reward deficiency syndrome’. The fragment length identified most often is 440 or 480 bp, with 480 as the primary fragment in obesity. The DBH gene is similar to the DRD2 in that it also contains a Taq I restriction. Two allelic variants are also identified, B1 and B2. The B1 allele contains no Taq I site and produces a 316 bp fragment while the B2 does cleave, exhibiting an 86 bp and a 230 bp fragment after enzyme digestion. The presence of one or more of the aberrant alleles could be associated with and a predisposing factor to obesity.Item Single Nucleotide Polymorphisms and Haplotype Analyses of Complex Medical Disorders(2008-05-01) Gonzalez, Suzanne D.; Arthur Eisenberg; Robert Luedtke; Rustin ReevesGonzalez, Suzanne D., Doctor of Philosophy. Cell Biology and Genetics. Single Nucleotide Polymorphisms and Haplotype Analyses of Complex Medical Disorders. Number of Pages: 129. Number of Tables: 25. Number of Illustrations: 5. Number of Titles Included in References: 197. There has been great difficulty in identifying genes involved in complex disorders. The complex genetic basis of these diseases indicates that either several genes act together to cause disease, or genetic heterogeneity is present in the population. This dissertation was aimed at developing new assays to identify polymorphisms in novel candidate genes that potentially contribute to two classes of common complex disorders: psychiatric diseases and metabolic disorders. Genotyping assays were developed to investigate single nucleotide polymorphisms (SNPs) and haplotypes in complex genetic disorders using multiplexed SNP panels, restriction fragment length polymorphism technology, and cycle sequencing platforms. An introduction to the study is provided in Chapter 1. Manuscripts focus on association studies of candidate genes in Bipolar Disorder and Schizophrenia (Chapter 2), Type 2 Diabetes, Hypertension and Metabolic Syndrome (Chapter 3), and baseline blood pressure in African Americans (Chapter 4). The summary of these manuscripts (Chapter 5) describes the significant associations made between SNPs/haplotypes in psychiatric and metabolic complex genetic disorders. Significant genetic associations of SNPs within the PHLPP gene were detected among schizophrenics (Chapter 2). The G allele of SNP rs8087170 was associated with the control population with the T allele of SNP rs12966002 was found only in schizophrenics. A significant variance was detected at SNP rs12457020 between bipolar and schizophrenic datasets, as there was a 10 fold increase in the A allele in the bipolar group. Significant associations of ATP1A2 5’ SNPs C-1489T and G-1253A were detected in metabolic syndrome and hypertensive groups (Chapter 3). Haplotypes based on these 3 SNPs were significantly associated with metabolic syndrome and hypertensive populations. Four linked ATP1A2 SNPs, G3756C, G3853A, C3913T and C3915T, were associated with baseline blood pressure (Chapter 4). Haplotypes associated with blood pressure in an ethnic specific manner. GGCC associated with lower blood pressures, while haplotype GGTT associated with higher blood pressures in African Americans. These studies provide new mechanisms to identify mutations and provide evidence supporting the pathophysiology of these disorders.