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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
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综合计算分析涉及调节性基因组元素,这些元素有助于脊柱裂变.

Paul Wolujewicz1, Vanessa Aguiar-Pulido2,1, Gaurav Thareja3

  • 1Center for Neurogenetics, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY.

Genetics in medicine open
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概括

这项研究确定了与脊柱裂 (SB) 相关的调节性DNA中的罕见遗传变异. 这些发现有助于通过确定关键的调节区域和受影响的途径来了解对SB的遗传倾向.

关键词:
深度学习是一种深度学习.基因间变异是基因间变异.神经管缺陷的神经管缺陷在拓上关联域 (TADs).转录因子结合位点 (TFBS)

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科学领域:

  • 基因组学就是基因组学.
  • 发展生物学 发展生物学
  • 生物信息学是一种生物信息学.

背景情况:

  • 脊柱裂 (SB) 是由复杂的遗传相互作用导致的,这些相互作用会破坏神经管的闭合.
  • 了解基因组网络对于识别SB风险因素至关重要.

研究的目的:

  • 为了识别与脊椎裂 (SB) 病理生理学相关的全基因组调节签名.
  • 描述罕见的监管变体在SB发展中的作用.

主要方法:

  • 使用非向的全基因组方法分析罕见单核酸和副本数变异 (rSNV和rCNV) 的调节区域.
  • 采用深度学习框架来优先考虑功能相关的变异,并识别目标基因.
  • 比较了SB患者和健康对照组的变体数据.

主要成果:

  • 在转录因子结合位点 (TFBS) 中确定了特定的rSNV,特别是CCCTC结合因子结合位点,区分SB病例.
  • 优先变异涉及的基因涉及蛋白质运输,乳毛组装和中枢神经系统发育.
  • 检测到罕见的副本数变异 (rCNVs) 破坏基因调节网络和3D基因组架构,包括脑特异性增强剂.

结论:

  • 这项研究为了解基因组调节性DNA变异对SB遗传倾向的贡献提供了宝贵的资源.
  • 提供了对SB发展背后的分子机制的见解.