Folate and vitamin B12 metabolism in neural tube defects

分子发病机制的研究重点是定义基因的变化，这些变化是遗传对常见疾病（如癌症和出生缺陷）的易感性的基础。叶酸代谢的改变与肿瘤形成和出生缺陷有关。叶酸基因也参与DNA的甲基化。我们正在寻找与叶酸、蛋氨酸和同型半胱氨酸代谢相关的基因的遗传变异。受癌症或脊柱裂影响的个体将接受这些变异的检测。在患病个体中发现的频率较高的变异将有助于我们识别与风险相关的基因。已经鉴定了30多种叶酸相关基因的变体。其中一部分已经在脊柱裂家庭中进行了测试。初步证据表明，这些新的变异中有两种与脊柱裂风险有关。我们将在实验系统中测试这些变体的功能后果。将在患有癌症的个体中测量相同变体的频率。如果得到证实，这两个基因将增加我们对神经管缺陷和癌症风险的理解。

Research in the Molecular Pathogenesis is focused on defining changes in the genes that underlie inherited susceptibilities to common diseases such as cancer and birth defects. Changes in folate metabolism are correlated tumor formation and birth defects. Folate genes are also involved in the methylation of DNA. We are searching for genetic variants in genes related to folate, methionine and homocysteine metabolism. Individuals affected with cancer or spina bifida will be tested for these variants. Variants found at higher frequency in individuals with disease will help us identify genes associated with risk. More than 30 variants in folate related genes have been identified. A portion of these have been tested in spina bifida families. Initial evidence suggests that two of these new variants are associated with spina bifida risk. We will test the function consequences of these variants in experimental systems. The frequency of the same variants will be measured in individuals with cancer. If confirmed, these two genes will add to our understanding of neural tube defects and cancer risk.