Zoology - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/66

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Author: search.filters.author.Changotra, Harish

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    ATG5: A central autophagy regulator implicated in various human diseases
    (John Wiley and Sons Ltd, 2022-09-05T00:00:00) Changotra, Harish; Kaur, Sargeet; Yadav, Suresh Singh; Gupta, Girdhari Lal; Parkash, Jyoti; Duseja, Ajay
    Autophagy, an intracellular conserved degradative process, plays a central role in the renewal/recycling of a cell to maintain the homeostasis of nutrients and energy within the cell. ATG5, a key component of autophagy, regulates the formation of the autophagosome, a hallmark of autophagy. ATG5 binds with ATG12 and ATG16L1 resulting in E3 like ligase complex, which is necessary for autophagosome expansion. Available data suggest that ATG5 is indispensable for autophagy and has an imperative role in several essential biological processes. Moreover, ATG5 has also been demonstrated to possess autophagy-independent functions that magnify its significance and therapeutic potential. ATG5 interacts with various molecules for the execution of different processes implicated during physiological and pathological conditions. Furthermore, ATG5 genetic variants are associated with various ailments. This review discusses various autophagy-dependent and autophagy-independent roles of ATG5, highlights its various deleterious genetic variants reported until now, and various studies supporting it as a potential drug target. � 2022 John Wiley & Sons Ltd.
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    Association of IRGM gene promoter polymorphisms with hepatitis B virus infection
    (John Wiley and Sons Inc, 2022-06-04T00:00:00) Sharma, Ambika; Duseja, Ajay; Parkash, Jyoti; Changotra, Harish
    Background: In response to intracellular pathogens, the autophagy gene IRGM plays an essential role in the innate immune response. Various identified IRGM gene risk loci are associated with several diseases but, so far, no study is available that shows the association of IRGM with hepatitis B virus (HBV) infection. Methods: We genotyped promoter variants (rs4958842, rs4958843, and rs4958846) of IRGM in HBV infected patients (551) and healthy controls (247) for their role in HBV infection. The genotyping was performed by applying methods developed in our laboratory and various biochemical parameters were assessed applying commercially available kits. Results: Data analysis has shown that the mutant allele A of rs4958842 plays a role in the protection from HBV infection in various genetic models that includes allelic, co-dominant and dominant models with the respective statistical data: allelic (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.48�0.78; p = 0.0003), co-dominant (OR = 0.52; 95% CI = 0.38�0.71; p = 0.0008) and dominant (OR = 0.51; 95% CI = 0.38�0.70, p = 0.0004). In chronic hepatitis B (CHB), protective association was observed in the allelic (OR = 0.48; 95% CI = 0.35�0.65, p = 0.0004), co-dominant (OR = 0.38; 95% CI = 0.26�0.54, p = 0.0004) and dominant (OR = 0.38; 95% CI = 0.26�0.54, p = 0.0002) models. Mutant allele C of rs49598843 was associated with the risk of CHB in co-dominant (OR = 1.52; 95% CI = 1.07�2.16, p = 0.04) and dominant (OR = 1.41; 95% CI = 1.00�2.00, p = 0.04) models. The mutant allele C of rs4958846 decreased the risk of HBV infection in allelic (OR = 0.74; 95% CI = 0.59�0.92, p = 0.01), dominant (OR = 0.72; 95% CI = 0.53�0.98, p = 0.05), homozygous (OR = 0.42; 95% CI = 0.24�0.74, p = 0.01) and recessive (OR = 0.42; 95% CI = 0.24�0.74, p = 0.0004) models. However, in the asymptomatic group, it was associated with the increased chance of HBV infection. Haplotypes, ATT (OR = 0.47; 95% CI = 0.33�0.68, p = 0.001) and GTC (OR = 0.68; 95% CI = 0.51�0.92, p = 0.01) protect, whereas GTT (OR = 2.01; 95% CI = 1.55�2.60, p < 0.0001) predisposes the individuals to HBV infection. All of these p�values mentioned here were obtained after performing Bonferroni correction. Conclusions: In conclusion, our findings revealed that mutant allele A of rs4958842, mutant allele C of rs4958843 and rs4958846 were associated with hepatitis B virus infection in the North Indian population. � 2022 John Wiley & Sons Ltd.
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    Investigating regulatory signatures of human autophagy related gene 5 (ATG5) through functional in silico analysis
    (Elsevier B.V., 2016) Vij, Avni; Randhawa, Rohit; Parkash, Jyoti; Changotra, Harish; Vij, A.; Randhawa, R.; Parkash, J.; Changotra, H.
    Autophagy is an essential, homeostatic process which removes damaged cellular proteins and organelles for cellular renewal. ATG5, a part of E3 ubiquitin ligase-like complex (Atg12-Atg5/Atg16L1), is a key regulator involved in autophagosome formation - a crucial phase of autophagy. In this study, we used different in silico methods for comprehensive analysis of ATG5 to investigate its less explored regulatory activity. We have predicted various physico-chemical parameters and two possible transmembrane models that helped in exposing its functional regions. Twenty four PTM sites and 44 TFBS were identified which could be targeted to modulate the autophagy pathway. Furthermore, LD analysis identified 3 blocks of genotyped SNPs and 2 deleterious nsSNPs that may have damaging impact on protein function and thus could be employed for carrying genome-wide association studies. In conclusion, the information obtained in this study could be helpful for better understanding of regulatory roles of ATG5 and provides a base for its implication in population-based studies. ? 2016 Elsevier B.V.