scholarly journals Contribution of Common Variants in GABRG2, RELN and NRG3 and Interaction Networks to the Risk of Hirschsprung Disease

2016 ◽  
Vol 40 (3-4) ◽  
pp. 509-526 ◽  
Author(s):  
Yang Wang ◽  
Jun Wang ◽  
Ying Zhou ◽  
Zhiyun Wei ◽  
Yongtao Xiao ◽  
...  
Keyword(s):  
Genetic Interaction ◽  
Interaction Analysis ◽  
Hirschsprung Disease ◽  
Gene Interaction ◽  
Han Chinese ◽  
Interaction Networks ◽  
Common Variants ◽  
Chinese Origin ◽  
Ptch1 Gene ◽  
Normal Controls

Background: Hirschsprung disease (HSCR) is a complex and heterogeneous disorder, characterized by a deficit in enteric nervous system. Genome-wide studies implied GABRG2, RELN and NRG3 might be involved in HSCR etiology. Here, we aimed to assess genetic variants in GABRG2, RELN and NRG3 that may confer susceptibility to HSCR and explore genetic interaction networks in HSCR. Methods: Using a strategy that combined case-control study and gene-gene interaction analysis with the MassArray system, we evaluated 24 polymorphisms within GABRG2, RELN and NRG3 in 104 HSCR cases and 151 normal controls of Han Chinese origin. Results: We observed that seven polymorphisms showed statistically significant differences between HSCR subjects and normal controls. For each of the three genes, the haplotypes which combined eight markers were the most significant. Moreover, we recruited SNPsyn, GO enrichment and MDR analyses to interrogate the interactions among GABRG2, RELN, NRG3 and our previous identified PTCH1 gene. Significant interaction networks were found among GABRG2, RELN, and PTCH1. Conclusion: We provide a first indication that common variants of GABRG2, RELN and NRG3 and the GABRG2-RELN-PTCH1 interaction networks might confer altered susceptibility to HSCR in the Han Chinese population, suggesting a potential mechanism underlying HSCR pathogenesis.

scholarly journals Common Genetic Variations in Patched1 (PTCH1) Gene and Risk of Hirschsprung Disease in the Han Chinese Population

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e75407 ◽  
Author(s):  
Yang Wang ◽  
Jun Wang ◽  
Weihua Pan ◽  
Ying Zhou ◽  
Yongtao Xiao ◽  
...  
Keyword(s):  
Chinese Population ◽  
Hirschsprung Disease ◽  
Genetic Variations ◽  
Han Chinese ◽  
Han Chinese Population ◽  
Ptch1 Gene

Common variants of NRG1 and ITGB4 confer risk of Hirschsprung disease in Han Chinese population

2020 ◽  
Vol 55 (12) ◽  
pp. 2758-2765
Author(s):  
Zhiliang Wei ◽  
Xianxian Yu ◽  
Wenjie Wu ◽  
Meirong Bai ◽  
Yanjiao Lu ◽  
...  
Keyword(s):  
Chinese Population ◽  
Hirschsprung Disease ◽  
Han Chinese ◽  
Common Variants ◽  
Han Chinese Population

scholarly journals Association Analysis of Variants of DSCAM and BACE2 With Hirschsprung Disease Susceptibility in Han Chinese and Functional Evaluation in Zebrafish

2021 ◽  
Vol 9 ◽  
Author(s):  
Yan-Jiao Lu ◽  
Wen-Wen Yu ◽  
Meng-Meng Cui ◽  
Xian-Xian Yu ◽  
Huan-Lei Song ◽  
...  
Keyword(s):  
Rare Variants ◽  
Hirschsprung Disease ◽  
Han Chinese ◽  
Chromosome 21 ◽  
Enteric Neurons ◽  
Functional Evaluation ◽  
Nucleotide Polymorphisms ◽  
Common Variants ◽  
Predisposing Factor ◽  
Functional Roles

Hirschsprung disease (HSCR) has a higher incidence in children with Down syndrome (DS), which makes trisomy 21 a predisposing factor to HSCR. DSCAM and BACE2 are close together on the HSCR-associated critical region of chromosome 21. Common variants of DSCAM and rare variants of BACE2 were implicated to be associated with sporadic HSCR. However, the submucosal neuron defect of DS mouse model could not be rescued by normalization of Dscam. We aimed to explore the contribution of DSCAM and BACE2 to the development of the enteric nervous system (ENS) and HSCR susceptibility. We genotyped 133 tag single-nucleotide polymorphisms (SNPs) in DSCAM and BACE2 gene region in 420 HSCR patients and 1,665 controls of Han Chinese. Expression of DSCAM and BACE2 homologs was investigated in the developing gut of zebrafish. Overexpression and knockdown of the homologs were performed in zebrafish to investigate their roles in the development of ENS. Two DSCAM SNPs, rs430255 (PAddtive = 0.0052, OR = 1.36, 95% CI: 1.10–1.68) and rs2837756 (PAddtive = 0.0091, OR = 1.23, 95% CI: 1.05–1.43), showed suggestive association with HSCR risk. Common variants in BACE2 were not associated with HSCR risk. We observed dscama, dscamb, and bace2 expression in the developing gut of zebrafish. Knockdown of dscama, dscamb, and bace2 caused a reduction of enteric neurons in the hindgut of zebrafish. Overexpression of DSCAM and bace2 had no effects on neuron number in the hindgut of zebrafish. Our results suggested that common variation of DSCAM contributed to HSCR risk in Han Chinese. The dysfunction of both dscams and bace2 caused defects in enteric neuron, indicating that DSCAM and BACE2 might play functional roles in the occurrence of HSCR. These novel findings might shed new light on the pathogenesis of HSCR.

scholarly journals Actin-Related Protein 6 (Arp6) Influences Double-Strand Break Repair in Yeast

2021 ◽  
Vol 1 (2) ◽  
pp. 225-238
Author(s):  
Mohsen Hooshyar ◽  
Daniel Burnside ◽  
Maryam Hajikarimlou ◽  
Katayoun Omidi ◽  
Alexander Jesso ◽  
...  
Keyword(s):  
Dna Damage ◽  
Chromatin Remodeling ◽  
Genetic Interaction ◽  
Interaction Analysis ◽  
Strand Break ◽  
Dna Double Strand Breaks ◽  
Dsb Repair ◽  
Dna Damaging Agents ◽  
Repair Efficiency ◽  
Chromosomal Breaks

DNA double-strand breaks (DSBs) are the most deleterious form of DNA damage and are repaired through non-homologous end-joining (NHEJ) or homologous recombination (HR). Repair initiation, regulation and communication with signaling pathways require several histone-modifying and chromatin-remodeling complexes. In budding yeast, this involves three primary complexes: INO80-C, which is primarily associated with HR, SWR1-C, which promotes NHEJ, and RSC-C, which is involved in both pathways as well as the general DNA damage response. Here we identify ARP6 as a factor involved in DSB repair through an RSC-C-related pathway. The loss of ARP6 significantly reduces the NHEJ repair efficiency of linearized plasmids with cohesive ends, impairs the repair of chromosomal breaks, and sensitizes cells to DNA-damaging agents. Genetic interaction analysis indicates that ARP6, MRE11 and RSC-C function within the same pathway, and the overexpression of ARP6 rescues rsc2∆ and mre11∆ sensitivity to DNA-damaging agents. Double mutants of ARP6, and members of the INO80 and SWR1 complexes, cause a significant reduction in repair efficiency, suggesting that ARP6 functions independently of SWR1-C and INO80-C. These findings support a novel role for ARP6 in DSB repair that is independent of the SWR1 chromatin remodeling complex, through an apparent RSC-C and MRE11-associated DNA repair pathway.

scholarly journals Interactions between Gene Variants within the COL1A1 and COL5A1 Genes and Musculoskeletal Injuries in Physically Active Caucasian

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1056
Author(s):  
Katarzyna Leźnicka ◽  
Ewelina Żyźniewska-Banaszak ◽  
Magdalena Gębska ◽  
Anna Machoy-Mokrzyńska ◽  
Anna Krajewska-Pędzik ◽  
...  
Keyword(s):  
Significant Interaction ◽  
Interaction Analysis ◽  
Gene Interaction ◽  
Musculoskeletal Injury ◽  
Musculoskeletal Injuries ◽  
Caucasian Population ◽  
Muscle Area ◽  
Physically Active ◽  
Haplotype Combination ◽  
Injury Status

The COL1A1 and COL5A1 variants have been associated with the risk of musculoskeletal injuries. Therefore, the main aim of the study was to investigate the association between three polymorphisms within two genes (rs1800012 in COL1A1, as well as rs12722 and rs13946 in COL5A1) and the reported, yet rarely described in the literature, injuries of the joint and muscle area in a physically active Caucasian population. Polish students (n = 114) were recruited and divided into the following two groups: students with (n = 53) and without (n = 61) injures. Genotyping was carried out using real-time PCR. The results obtained revealed a statistically significant association between rs1800012 COL1A1 and injury under an overdominant model. Specifically, when adjusted for age and sex, the GT heterozygotes had a 2.2 times higher chance of being injured compared with both homozygotes (TT and GG, 95% CI 0.59–5.07, p = 0.040). However, no significant interaction between the COL5A1 variants, either individually or in haplotype combination, and susceptibility to injury were found. In addition, the gene–gene interaction analysis did not reveal important relationships with the musculoskeletal injury status. It was demonstrated that rs1800012 COL1A1 may be positively associated with physical activity-related injuries in a Caucasian population. Harboring the specific GT genotype may be linked to a higher risk of being injured.

Common variants in IL17F gene contributed to the risk of hip osteoarthritis susceptibility in Han Chinese population

2020 ◽  
Vol 23 (8) ◽  
pp. 1050-1056
Author(s):  
Tianyun Zhao ◽  
Chi Ma ◽  
Wei Wang ◽  
Bin Zhao ◽  
Baopin Xie ◽  
...  
Keyword(s):  
Chinese Population ◽  
Hip Osteoarthritis ◽  
Han Chinese ◽  
Common Variants ◽  
Han Chinese Population
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