Neural Tube Defects and Folate Pathway Genes: Family-Based Association Tests of Gene–Gene and Gene–Environment Interactions

BACKGROUND: Folate metabolism pathway genes have been examined for association with neural tube defects (NTDs) because folic acid supplementation reduces the risk of this debilitating birth defect. Most studies addressed these genes individually, often with different populations providing conflicting results. OBJECTIVES: Our study evaluates several folate pathway genes for association with human NTDs, incorporating an environmental cofactor: maternal folate supplementation. METHODS: In 304 Caucasian American NTD families with myelomeningocele or anencephaly, we examined 28 polymorphisms in 11 genes: folate receptor 1, folate receptor 2, solute carrier family 19 member 1, transcobalamin II, methylenetetrahydrofolate dehydrogenase 1, serine hydroxymethyl-transferase 1, 5,10-methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homo-cysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, betaine-homocysteine methyltransferase (BHMT), and cystathionine-beta-synthase. RESULTS: Only single nucleotide polymorphisms (SNPs) in BHMT were significantly associated in the overall data set; this significance was strongest when mothers took folate-containing nutritional supplements before conception. The BHMT SNP rs3733890 was more significant when the data were stratified by preferential transmission of the MTHFR rs1801133 thermolabile T allele from parent to offspring. Other SNPs in folate pathway genes were marginally significant in some analyses when stratified by maternal supplementation, MTHFR, or BHMT allele transmission. CONCLUSIONS: BHMT rs3733890 is significantly associated in our data set, whereas MTHFR rs1801133 is not a major risk factor. Further investigation of folate and methionine cycle genes will require extensive SNP genotyping and/or resequencing to identify novel variants, inclusion of environmental factors, and investigation of gene–gene interactions in large data sets

Способы перевода аббревиатур и сокращений в области компьютерных технологий (на примере русского и немецкого языков)

Выпускная квалификационная работа 75 с., 2 главы, 42 источника. Предмет исследования: способы перевода аббревиатур и сокращений в области компьютерных технологий с немецкого языка на русский язык. Объектом исследования: аббревиатуры и сокращения, относящиеся к области компьютерных технологий. Цель работы: выявить эффективные способы перевода аббревиатур и сокращений в области компьютерных технологий с немецкого языка на русский. Результаты исследования: были сформулированы особенности перевода аббревиатур и сокращений в области компьютерных технологий Степень внедрения/апробация работы: Было опубликовано две статьи Область применения: лингвистика, языкознание, переводоведение.Graduation thesis: 75 pg., 2 chapters, 42 resources. Subject of research: translation methods of acronyms and reductions in the field of computer technology from German into Russian. Object of research: Acronyms and reductions in the field of computer technology. Purpose of research: : to identify the translation methods of acronyms and reductions in the field of computer technology from German into Russian. Results of research: The features of the translation of acronyms and reductions in the area of computer technology has been revealed. Degree of implementation /work approbation: two articles were published. Field of application: Linguistic, theory of translatio

Human neural crest cells display molecular and phenotypic hallmarks of stem cells

The fields of both developmental and stem cell biology explore how functionally distinct cell types arise from a self-renewing founder population. Multipotent, proliferative human neural crest cells (hNCC) develop toward the end of the first month of pregnancy. It is assumed that most differentiate after migrating throughout the organism, although in animal models neural crest stem cells reportedly persist in postnatal tissues. Molecular pathways leading over time from an invasive mesenchyme to differentiated progeny such as the dorsal root ganglion, the maxillary bone or the adrenal medulla are altered in many congenital diseases. To identify additional components of such pathways, we derived and maintained self-renewing hNCC lines from pharyngulas. We show that, unlike their animal counterparts, hNCC are able to self-renew ex vivo under feeder-free conditions. While cross species comparisons showed extensive overlap between human, mouse and avian NCC transcriptomes, some molecular cascades are only active in the human cells, correlating with phenotypic differences. Furthermore, we found that the global hNCC molecular profile is highly similar to that of pluripotent embryonic stem cells when compared with other stem cell populations or hNCC derivatives. The pluripotency markers NANOG, POU5F1 and SOX2 are also expressed by hNCC, and a small subset of transcripts can unambiguously identify hNCC among other cell types. The hNCC molecular profile is thus both unique and globally characteristic of uncommitted stem cells

High Density SNP Screen in A Large Multiplex Neural Tube Defect Family Refines Linkage to Loci at 7p21-Pter And 2q33.1-35

Neural tube defects (NTDs) are considered complex with both genetic and environmental factors implicated. To date, no major causative genes have been identified in humans despite several investigations. The first genomewide screen in NTDs (Rampersaud et al. 2005) demonstrated evidence of linkage to chromosomes 7 and 10. This screen included forty-four multiplex families and consisted of 402 microsatellite markers spaced approximately 10 cM apart. Further investigation of the genomic screen data identified a single large multiplex family, pedigree 8776, as primarily driving the linkage results on chromosome 7

Evaluation of Current Methods of Testing Differential Gene expression and Beyond

One frequent question in the study of microarrys concerns the number of replicates required to obtain vaild data. We used the T-matrix data from the NCI-60 cancer cell lines dataset to investigate this question. Five testing methods were evaluated. We selected two cancer groups for comparisons, ovarian (OV) vs. breast (BR) and leukemias (LE) vs. renal carcinoma (RE), to perform hypothesis testing for detecting the genes expressed differentially between cancer groups. Our goal is to examine the pattern and performance of each testing method and the required sample size. The first four testing methods are t-test based methods with different strategies of computing sampling variance, including the uses of sampling variance, pooled variance, and common variance. The 5th test is a permutation test based on the t-test with pooled variance. Our results show that there are more genes with statistically significant differences in expression in the LE vs. RE comparison than between the OV vs. BR. The permutation works similarly to the t-test itself. Overall, the pooled variance approach proved a better strategy. For sample size, as expected, the number of significant genes increased as the number of cell lines increased for the same testing method. However, we found that the results derived from 3 cell lines are very different from the other results. It may imply that more than three cell lines or replicates are needed in the microarray study in order to attain enough power to detect the differential gene expressio

Support of linkage of Gerstmann-Sträussler-Scheinker syndrome to the prion protein gene on chromosome 20p12-pter

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a human transmissible spongiform encephalopathy recently linked to the human analog of the prion protein gene (PRNP) on chromosome 20p. We have studied a large German GSS family for linkage to PRNP and have obtained a peak lod score of 1.15 at a recombination fraction (θ) of 0.00. This result provides additional evidence that GSS is linked to a mutation in codon 102 of the PRNP gene. Combining our data with linkage data previously reported yields a peak lod score of 4.52 at θ = 0.0. No evidence for linkage heterogeneity was found in the combined data set

Human neural tube defects: developmental biology, epidemiology, and genetics

Abstract Birth defects (congenital anomalies) are the leading cause of death in babies under 1 year of age. Neural tube defects (NTD), with a birth incidence of approximately 1/1000 in American Caucasians, are the second most common type of birth defect after congenital heart defects. The most common presentations of NTD are spina bifida and anencephaly. The etiologies of NTDs are complex, with both genetic and environmental factors implicated. In this manuscript, we review the evidence for genetic etiology and for environmental influences, and we present current views on the developmental processes involved in human neural tube closure

Allelic Differences in the Brain-Derived Neurotrophic Factor Val66Met Polymorphism in Late-Life Depression

The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with cognitive and neuroimaging changes. The authors examined the relationship between this polymorphism and depression in an elderly sample, hypothesizing that the Met66 allele would be associated with late-life depression. A total of 245 elderly depressed white subjects and 94 elderly comparison white subjects completed clinical assessments and provided a blood sample for genotyping. Subjects were dichotomized as either homozygous for the Val66 allele or Met66 allele carriers. Gene frequencies were compared between groups, with separate analyses examining for differences in gene frequencies based on age of depression onset, family history, and depression history. Logistic regression models examined the relationship between genotype and depression after controlling for age, sex, and race. Depressed subjects were more likely to be Met66 allele carriers than were comparison subjects (38.8% versus 24.4%; χ2 = 6.13, 1 df, p = 0.0133). This relationship remained significant after controlling for covariates (Wald χ2 = 5.10, 1 df, p = 0.024; odds ratio: 1.92, 95% confidence interval: 1.09–3.38). There were no significant relationships between genotype and age of onset, number of episodes, or family history of depression. Met66 allele carriers have almost double the odds of having geriatric depression than do Val66 allele homozygotes. This polymorphism was unrelated to other clinical characteristics of depression in later life