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首页> 外文学位 >Association of folate metabolic pathway genes with human spina bifida meningomyelocele.
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Association of folate metabolic pathway genes with human spina bifida meningomyelocele.

机译：叶酸代谢途径基因与人脊柱裂脑膜脊髓膨出症的关联。

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摘要

Neural tube defects including spina bifida meningomyelocele (SBMM) are common malformations of the brain and spinal cord, and include all abnormalities resulting from lack of closure of the developing neural tube during embryological development.The specific aims of this study were to determine if single nucleotide polymorphic variants (SNPs) in the folate/homocysteine metabolic pathway genes confer a risk for NTD susceptibility within this SBMM population.In completion of the first specific aim, two novel SNPs were identified in the FOLR1 gene in Chromosome 11of patients including one in non-coding exon 1 with a C &rarr T transition at nucleotide position 71578317 and another in non-coding exon 3 with a T &rarr G transversion at nucleotide position 71579123. It will be important to determine if these variants are present in the respective parents of these individuals. If they are in fact de novo variants, then these SNPs may be more likely to contribute to the birth defect.The second project aim was to analyze genotypes associated with SBMM risk by transmission disequilibrium tests (TDT) and association was detected on several SNPs across the folate metabolic pathway genes in this population. SNPs with significant RC-TDT values were found within the DHFR gene (rs1650723), the MTRR gene (rs327592), the FOLR2 gene (rs13908), four tightly linked variants in the FOLR3 gene (rs7925545, rs7926875, rs7926987, rs7926360) and a variant in the SLC19A1 gene (rs1888530). The product of each of these genes performs a vital function in the folate metabolic pathway. It is conceivable, therefore, that if the individual SNP or SNPs can be proven to perturb the function in some way that they may be involved in the disruption of folate metabolism and in the resulting birth defect. Validating the results of this study in other independent populations will further strengthen the evidence that dysfunction of folate enzymes and receptors may confer SBMM risk in humans.
机译：包括脊柱裂脑膜脊髓膨出症（SBMM）在内的神经管缺陷是大脑和脊髓的常见畸形，包括由于胚胎发育过程中发育中的神经管缺乏闭合而导致的所有异常。本研究的具体目的是确定单核苷酸是否叶酸/同型半胱氨酸代谢途径基因中的多态性变异（SNP）赋予该SBMM人群NTD易感性的风险。完成第一个特定目标后，在11号染色体患者的FOLR1基因中鉴定出两个新的SNP，其中一个在非编码外显子1在核苷酸位置71578317具有C＆rarr T转变，而另一个在非编码外显子3中在核苷酸位置71579123具有T＆rarr G转变。确定这些变异体是否存在于这些个体各自的亲本中，这一点很重要。 。如果它们实际上是从头变异，那么这些SNP可能更可能导致出生缺陷。第二个项目目标是通过传播不平衡测试（TDT）分析与SBMM风险相关的基因型，并在多个SNP上检测到关联该人群中的叶酸代谢途径基因。在DHFR基因（rs1650723），MTRR基因（rs327592），FOLR2基因（rs13908），FOLR3基因中的四个紧密连接的变体（rs7925545，rs7926875，rs7926987，rs7926360）和a中发现了具有显着RC-TDT值的SNP。 SLC19A1基因（rs1888530）中的变异体。这些基因的每一个的产物在叶酸代谢途径中起着至关重要的作用。因此，可以想象，如果单个SNP或SNP被证明以某种方式扰乱了功能，则它们可能参与叶酸代谢的破坏并导致出生缺陷。在其他独立人群中验证这项研究的结果将进一步加强证据，证明叶酸酶和受体功能障碍可能会给人类带来SBMM风险。

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  • 作者

    O'Byrne, Michelle R.;

  • 作者单位

    The University of Texas School of Public Health.;

  • 授予单位 The University of Texas School of Public Health.;
  • 学科 Biology Molecular.Biology Genetics.Health Sciences Epidemiology.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 205 p.
  • 总页数 205
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
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