Polymorphisms

Polymorphism or variation in DNA sequence can affect individual phenotypes such as color of skin or eyes, susceptible to diseases, and respond to drug, vaccine, chemical, and pathogen. It occurs more often than mutations (frequency ≥ 1%). The common polymorphism is single nucleotide polymorphism (SNP) which is a single base change in a DNA sequence that occurs most commonly in the human genome. SNPs have been used as molecular markers in a wide range of studies. Genome-wide association studies (GWAS) searches for SNPs that occur more frequently in person with a particular disease than in person without the disease and pinpoint genes or regions that may contribute to a risk of disease. This topic describes about polymorphisms, SNPs, GWAS, linkage disequilibrium (LD), minor allele frequency, haplotype, method for SNP genotyping, and application of SNPs and genome-wide association study in human diseases and drug development

Teaching macromolecules and its metabolism sequentially improves learning abilityin biochemistry course of medical students

Biochemistry for medical student is a subject that focuses on structure and function of macromolecules and their metabolic pathways in living organism. This subject is quite difficult for students to understand because they have to imagine the interactions that occur in the cell at the molecular level. Learning sequence of each topic is exhibited as an important factor that may affect learning ability of students. Therefore, in this study the sequences of topics were evaluated by comparing between the parts of macromolecules either teaching separately or in combination with its metabolism sequentially. The analysis was done using the examination scores of different medical student groups at Srinakharinwirot University that studied different topic sequences. The data analysis revealed that the new topic sequence rearrangement in which each of macromolecules was taught following by its metabolic pathway was significantly better (p < 0.05) than the former sequences. This data demonstrated that the improved topic sequences are important for learning ability which will be useful for teaching development in the future

Association of <it>CTXN3-SLC12A2</it> polymorphisms and schizophrenia in a Thai population

Abstract Background A genome-wide association study (GWAS) combined with brain imaging as a quantitative trait analysis revealed that the SNPs near CTXN3-SLC12A2 region were related to forebrain development and stress response which involved in schizophrenia. In the present study, the SNPs in this region were analyzed for association with schizophrenia in a Thai population. Methods A total of 115 schizophrenia and 173 unrelated normal controls with mean age of 37.87 ± 11.8 and 42.81 ± 6.0 years, respectively, were included in this study. Genotyping was performed using polymerase chain reaction and high-resolution melting (HRM) analysis. The difference in genotype distribution between patient and control was assessed by Chi-square test of the SPSS software. Results We found a significant association between the GWAS-discovered SNP, rs245178, with the risk of schizophrenia in the Thai population [P = 0.006, odds ratio for the minor G allele: 0.62(0.46–0.83)]. Additionally, another potential SNP, rs698172, which was in moderate linkage disequilibrium with rs245178, also showed strong association with schizophrenia [P = 0.003, odds ratio for minor T allele: 0.61(0.46–0.82)]. This association remained significant at 5% level after the Bonferroni correction for multiple testing. Conclusions This study shows that two SNPs in intergenic of the CTXN3 and SLC12A2 genes, rs245178 and rs698172, are associated with risk of schizophrenia in Thai population. Further study is required for clarification the role of genetic variation around these SNPs in expression pattern of the CTXN3 and SLC12A2 genes, which may be involved in schizophrenia pathogenesis.</p

Polymorphisms in nitric oxide synthase and endothelin genes among children with obstructive sleep apnea.

BackgroundObstructive sleep apnea (OSA) is associated with adverse and interdependent cognitive and cardiovascular consequences. Increasing evidence suggests that nitric oxide synthase (NOS) and endothelin family (EDN) genes underlie mechanistic aspects of OSA-associated morbidities. We aimed to identify single nucleotide polymorphisms (SNPs) in the NOS family (3 isoforms), and EDN family (3 isoforms) to identify potential associations of these SNPs in children with OSA.MethodsA pediatric community cohort (ages 5-10 years) enriched for snoring underwent overnight polysomnographic (NPSG) and a fasting morning blood draw. The diagnostic criteria for OSA were an obstructive apnea-hypopnea Index (AHI) &gt;2/h total sleep time (TST), snoring during the night, and a nadir oxyhemoglobin saturation &lt;92%. Control children were defined as non-snoring children with AHI &lt;2/h TST (NOSA). Endothelial function was assessed using a modified post-occlusive hyperemic test. The time to peak reperfusion (Tmax) was considered as the indicator for normal endothelial function (NEF; Tmax&lt;45 sec), or ED (Tmax ≥ 45 sec). Genomic DNA from peripheral blood was extracted and allelic frequencies were assessed for, NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), endothelin receptor A, EDNRA, (27 SNPs), and endothelin receptor B, EDNRB (23 SNPs) using a custom SNPs array. The relative frequencies of NOS-1,-2, and -3, and EDN-1,-2,-3,-EDNRA, and-EDNRB genotypes were evaluated in 608 subjects [128 with OSA, and 480 without OSA (NOSA)]. Furthermore, subjects with OSA were divided into 2 subgroups: OSA with normal endothelial function (OSA-NEF), and OSA with endothelial dysfunction (OSA-ED). Linkage disequilibrium was analyzed using Haploview version 4.2 software.ResultsFor NOSA vs. OSA groups, 15 differentially distributed SNPs for NOS1 gene, and 1 SNP for NOS3 emerged, while 4 SNPs for EDN1 and 1 SNP for both EDN2 and EDN3 were identified. However, in the smaller sub-group for whom endothelial function was available, none of the significant SNPs was retained due to lack of statistical power.ConclusionsDifferences in the distribution of polymorphisms among NOS and EDN gene families suggest that these SNPs could play a contributory role in the pathophysiology and risk of OSA-induced cardiovascular morbidity. Thus, analysis of genotype-phenotype interactions in children with OSA may assist in the formulation of categorical risk estimates

Genetic variance in nitric oxide synthase and endothelin genes among children with and without endothelial dysfunction.

BackgroundThe presence of endothelial dysfunction (ED) constitutes an early risk factor for cardiovascular disease (CVD) in children. Nitric oxide (NO) and endothelin (EDN) are generated in endothelial cells and are critical regulators of vascular function, with ED resulting from an imbalance between these two molecules. We hypothesized that genetic variants in NO synthase and EDN isoforms and its receptors (EDNRA and EDNRB) may account for a proportion of the risk for ED in developing children.MethodsConsecutive children (ages 5-10 years) were prospectively recruited from the community. Time to peak post-occlusive reperfusion (Tmax) was considered as the indicator of either normal endothelial function (NEF; Tmax &lt; 45 sec) or ED (Tmax ≥ 45 sec). Lipid profiles, high sensitivity C-reactive protein (hsCRP), fasting glucose and insulin were assayed using ELISA. Genomic DNA from peripheral blood was extracted and genotyped for NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), EDNRA (27 SNPs), and EDNRB (23 SNPs) using a custom SNPs array. Linkage disequilibrium was analyzed using Haploview version 4.2 software.ResultsThe relative frequencies of SNPs were evaluated in 122 children, 84 with NEF and 38 with ED. The frequencies of NOS1 (11 SNPs), and EDN1 (2 SNPs) were differentially distributed between NEF vs. ED, and no significant differences emerged for all other genes. Significant SNPs for NOS1 and EDN1 SNPs were further validated with RT-PCR.ConclusionsGenetic variants in the NOS1 and EDN1 genes appear to account for important components of the variance in endothelial function, particularly when concurrent risk factors such as obesity exist. Thus, analysis of genotype-phenotype interactions in children at risk for ED will be critical for more accurate formulation of categorical CVD risk estimates

RESEARCH Open Access Genetic variance in Nitric Oxide Synthase and Endothelin Genes among children with and

Background: The presence of endothelial dysfunction (ED) constitutes an early risk factor for cardiovascular disease (CVD) in children. Nitric oxide (NO) and endothelin (EDN) are generated in endothelial cells and are critical regulators of vascular function, with ED resulting from an imbalance between these two molecules. We hypothesized that genetic variants in NO synthase and EDN isoforms and its receptors (EDNRA and EDNRB) may account for a proportion of the risk for ED in developing children. Methods: Consecutive children (ages 5–10 years) were prospectively recruited from the community. Time to peak postocclusive reperfusion (Tmax) was considered as the indicator of either normal endothelial function (NEF; Tmax &lt; 45 sec) or ED (Tmax ≥ 45 sec). Lipid profiles, high sensitivity C-reactive protein (hsCRP), fasting glucose and insulin were assayed using ELISA. Genomic DNA from peripheral blood was extracted and genotyped for NOS1 (209 SNPs), NOS2 (122 SNPs)