Biomedical subjects

Audesh Bhat

Publications and source records attributed to Audesh Bhat.

5 recordsLinked to original sources

PubMed2026

Exploiting DNA damage tolerance for precision oncology.

Unresolved DNA lesions trigger replication stress, forcing cancer cells to hijack DNA damage tolerance (DDT) networks, specifically translesion synthesis (TLS) and template switching, to sustain replication. While DDT prevents lethal fork collapse, error-prone TLS drives mutagenesis, tumor evolution, chemoresistance and radioresistance. Proliferating cell nuclear antigen post-translational modifications dynamically govern pathway selection. Cancer cells exploit this plasticity, creating actionable vulnerabilities such as postreplicative single-stranded DNA gaps. Emerging inhibitors targeting TLS polymerases, upstream regulators such as ubiquitin-specific peptidase 1 (USP1), and critical protein-protein interactions offer unprecedented opportunities for precision oncology. By integrating DDT inhibition with biomarkers such as homologous recombination deficiency and tumor mutational burden, we can drive synthetic lethality, sensitize tumors to genotoxic agents, suppress treatment-induced mutagenesis, and potentially enhance responses to immunotherapy.

DDT↗

PubMed2024

CLOCK gene 3'UTR and exon 9 polymorphisms show a strong association with essential hypertension in a North Indian population.

BACKGROUND: Hypertension (HTN) is a medical condition characterized by persistent systolic and diastolic blood pressures of ≥ 140 mmHg and ≥ 90 mmHg, respectively. With more than 1200 million adult patients aged 30-79 years worldwide according to the latest WHO data, HTN is a major health risk factor; more importantly, 46% of patients are unaware of this condition. Essential hypertension (EH), also known as primary hypertension, is the predominant subtype and has a complex etiology that involves both genetic and non-genetic factors. Majority of living organisms are influenced by the light and dark cycle of a day and respond to these changes through an intricate clock referred to as the "biological clock" or "circadian rhythm". The connection between circadian rhythm and blood pressure is well established, with many studies supporting the role of circadian rhythm gene mutation(s)/polymorphism(s) in EH. To date, no such data are available from any Indian population. METHODS: This case‒control study was conducted on 405 EH patients and 505 healthy controls belonging to the Jammu region of North India after an informed consent was obtained from the participants. A total of three single nucleotide variants, two in the CLOCK gene (rs1801260 and rs34789226) and one in the BMAL1/ARNTL gene (rs6486121), were selected for genotyping. Genotyping was performed via the RFLP technique, and the applicable statistical analyses were performed via the SPSS and SNPStats programs. RESULTS: Logistic regression analysis revealed a statistically significant association of both CLOCK gene variants rs1801260 (T > C 3'UTR) and rs34789226 (C > T Exon 9) and a nonsignificant association of the BMAL1/ARNTL intronic variant rs6486121 (C > T) with EH. The 3'UTR variant showed a statistically significant association under the codominant (p < 0.0001), dominant (p < 0.0001), and recessive (p = 0.0004) models. In contrast, the exon 9 variant showed a statistically significant negative association under the codominant (p = 0.003) and dominant (p = 0.015) models only. The rs6486121/rs1801260 and rs1801260/rs34789226/rs6486121 haplotypes showed significant differences in their distribution between cases and controls (p < 0.0001). Certain genotypes and haplotypes were found more common in hypertensive males than females. CONCLUSION: This is a first report linking circadian rhythm gene polymorphisms with EH in any Indian population. The statistically significant association of the CLOCK gene 3'UTR and exon 9 polymorphisms with EH, highlight the potential role of this gene and probably other genes of the circadian pathway in the etiology of EH in the study population. Additionally, our study also revealed that certain genotypes are making males more susceptible to EH.

Humans↗

PubMed2006

The possible role of 10398A and 16189C mtDNA variants in providing susceptibility to T2DM in two North Indian populations: a replicative study.

The role of mitochondria in causing diseases is becoming evident as more and more studies are focusing on this organelle of the cell. This is largely attributed to its reactive oxygen species (ROS) production property. In the context of diabetes, ROS is suggested to trigger different forms of insulin resistance involving different mechanisms. The suggestive role of a mtDNA variant G10398A in increasing ROS production and the impaired response to oxidative stress due to T16189C variant is worth addressing as genetic susceptibility factors in type 2 diabetes mellitus (T2DM). A case control study on 312 T2DM cases and ethnically matched 466 controls involving two North Indian populations, referred as cohort 1 and cohort 2 (in a replicative study), was undertaken to test such a genetic association. A statistically significant association was observed for 10398A allele in both the cohorts [cohort1 (OR = 2.67 95% CI 1.77-4.00); cohort2 (OR = 1.76 95%CI 1.12-2.77)]. The analysis of G10398A/T16189C haplotypic combinations revealed that 10398A/16189C haplotype provides a risk in both the cohorts. To sum up the study suggests that 10398A and 16189C alleles provide susceptiblity to T2DM independently as well as together.

Adult↗

PubMed2005

Human mtDNA hypervariable regions, HVR I and II, hint at deep common maternal founder and subsequent maternal gene flow in Indian population groups.

We have analysed the hypervariable regions (HVR I and II) of human mitochondrial DNA (mtDNA) in individuals from Uttar Pradesh (UP), Bihar (BI) and Punjab (PUNJ), belonging to the Indo-European linguistic group, and from South India (SI), that have their linguistic roots in Dravidian language. Our analysis revealed the presence of known and novel mutations in both hypervariable regions in the studied population groups. Median joining network analyses based on mtDNA showed extensive overlap in mtDNA lineages despite the extensive cultural and linguistic diversity. MDS plot analysis based on Fst distances suggested increased maternal genetic proximity for the studied population groups compared with other world populations. Mismatch distribution curves, respective neighbour joining trees and other statistical analyses showed that there were significant expansions. The study revealed an ancient common ancestry for the studied population groups, most probably through common founder female lineage(s), and also indicated that human migrations occurred (maybe across and within the Indian subcontinent) even after the initial phase of female migration to India.

DNA, Mitochondrial↗

PubMed2004

Genetic affinity among five different population groups in India reflecting a Y-chromosome gene flow.

Four binary polymorphisms and four multiallelic short tandem repeat (STR) loci from the nonrecombining region of the human Y-chromosome were typed in different Indian population groups from Uttar Pradeh (UP), Bihar (BI), Punjab (PUNJ), and Bengal (WB) speaking the Indo-Aryan dialects and from South India (SI) with the root in the Dravidian language. We identified four major haplogroups [(P) 1+, (C and F) 2+, (R1a) 3, (K) 26+] and 114 combinations of Y-STR haplotypes. Analyses of the haplogroups indicated no single origin from any lineage but a result of a conglomeration of different lineages from time to time. The phylogenetic analyses indicate a high degree of population admixture and a greater genetic proximity for the studied population groups when compared with other world populations.

Alleles↗