Genetic variants ofIL-11associated with risk of Hirschsprung disease

2015 ◽  
Vol 27 (10) ◽  
pp. 1371-1377 ◽  
Author(s):  
L. H. Kim ◽  
H. S. Cheong ◽  
J.-G. Shin ◽  
J.-M. Seo ◽  
D.-Y. Kim ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Hirschsprung Disease

scholarly journals Genetic variants in RET, ARHGEF3 and CTNNAL1, and relevant interaction networks, contribute to the risk of Hirschsprung disease

Aging ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 4379-4393 ◽  
Author(s):  
Yang Wang ◽  
Qian Jiang ◽  
Hao Cai ◽  
Ze Xu ◽  
Wenjie Wu ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Hirschsprung Disease ◽  
Interaction Networks ◽  
Relevant Interaction

scholarly journals Whole-genome analysis of noncoding genetic variations identifies multigranular regulatory element perturbations associated with Hirschsprung disease

2020 ◽  
Author(s):  
Alexander Xi Fu ◽  
Kathy Nga-Chu Lui ◽  
Clara Sze-Man Tang ◽  
Ray Kit Ng ◽  
Frank Pui-Ling Lai ◽  
...  
Keyword(s):  
Neural Crest ◽  
Genetic Variants ◽  
Regulatory Element ◽  
Hirschsprung Disease ◽  
Regulatory Elements ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Whole Genome Analysis ◽  
Cell Stage

AbstractIt is widely recognized that the missing heritability of many human diseases is partially due to noncoding genetic variants, but there are multiple challenges that hinder the identification of functional disease-associated noncoding variants. The number of noncoding variants can be many times of coding variants; many of them are not functional but in linkage disequilibrium with the functional ones; different variants can have epistatic effects; different variants can affect the same genes or pathways in different individuals, and some variants are related to each other not by affecting the same gene but by affecting the binding of the same upstream regulator. To overcome these difficulties, we propose a novel analysis framework that considers convergent impacts of different genetic variants on protein binding, which provides multi-granular information about disease-associated perturbations of regulatory elements, genes, and pathways. Applying it to our whole-genome sequencing data of 918 short-segment Hirschsprung disease patients and matched controls, we identify various novel genes not detected by standard single-variant and region-based tests, functionally centering on neural crest migration and development. Our framework also identifies upstream regulators whose binding is influenced by the noncoding variants. Using human neural crest cells, we confirm cell-stage-specific regulatory roles three top novel regulatory elements on our list, respectively in the RET, RASGEF1A and PIK3C2B loci. In the PIK3C2B regulatory element, we further show that a noncoding variant found only in the affects the binding of the gliogenesis regulator NFIA, with a corresponding down-regulation of multiple genes in the same topologically associating domain.

Genetic Variation: Impact on Folate (and Choline) Bioefficacy

2010 ◽  
Vol 80 (45) ◽  
pp. 319-329 ◽  
Author(s):  
Allyson A. West ◽  
Marie A. Caudill
Keyword(s):  
Carbon Metabolism ◽  
Genetic Variants ◽  
Plasma Homocysteine ◽  
Water Soluble ◽  
Gene Interactions ◽  
Dietary Folate ◽  
Methyl Donors ◽  
Common Genetic Variants ◽  
One Carbon Metabolism ◽  
The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

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