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• Eighteen base pair (g.168_185) deletion allele of DJ-1 promoter is a risk factor for aged PD patients in eastern India. • The expression of DJ-1 is observed to be significantly reduced in the presence of both deletion and duplication variants. • REST, a transcription factor, can bind to the 18 bp insertion sequence of DJ-1 promoter and regulates its expression. • An 18 bp deletion or, duplication of DJ-1 promoter results in the loss of REST binding which compromises DJ-1 expression. Parkinson's disease (PD) is a progressive neurodegenerative disorder with a complex etiology. Presence of autosomal mutations in PARK7/DJ-1 gene has been associated with early-onset PD. Growing evidence has suggested that DJ-1 acts as a putative sensor of oxidative stress. Reduced levels of DJ-1 protein have been reported in the cerebrospinal fluid of sporadic PD patients. Several case-control association studies have identified DJ-1 g.168_185del (rs200968609) variants conferring susceptibility towards PD pathogenesis. Similarly, among the PD patients in eastern India, the deletion allele (g.168_185) of this DJ-1 promoter polymorphism was found to be associated with PD. Hence, we aimed to find out the functional contribution of this promoter variant of DJ-1 in PD pathogenesis. The expression of DJ-1 was observed to be significantly reduced in the presence of both deletion and duplication sequences as identified from the luciferase promoter activity assay. The transcription factor binding prediction tool identified DJ-1 promoter 18 bp insertion polymorphism as the only binding partner of REST (RE1 Silencing Transcription Factor). Transient Chromatin Immuno-precipitation (ChIP) assay further confirmed this prediction. Previous reports have highlighted the role of REST in regulating the expression of stress-responsive genes. Our study has identified the functional involvement of DJ-1 promoter variants and REST-mediated regulation of DJ-1 expression in PD pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: The promoter of an Indian isolate of the pararetrovirus Rice tungro bacilliform virus (RTBV-WB) contains a negative element downstream of the transcription start site (TSS), between nucleotide residues +58 and +195 (). To further characterize the element, we show, by using transient gus reporter gene assays in the cells of onion peel, rice calli and Arabidopsis leaves, that it down-regulates heterologous promoters CaMV35S and Maize ubiquitin. Quantitative measurements of transient GUS activity indicated more than 90% inhibition of reporter gene expression by the negative element. We also show, by reversing the orientation of the element downstream and by placing it in a position upstream to a constitutively expressing RTBV promoter, that the negative element is orientation- and position-independent, pointing towards its activity at the transcriptional and not post-transcriptional level. [Copyright &y& Elsevier]

The connective tissue growth factor gene plays important role in several biological processes and also responsive to hypoxia stress in fishes. The freshwater fish, Labeo rohita, highly cultured in Indian subcontinent for food, is reported as hypoxia sensitive but annotation and sequences of nuclear genes were not available for this species so far in the public domain, except some transcripts. In this study, an attempt was made for isolation and annotation of the CTGF gene in L. rohita using information of zebrafish from the same family. The CTGF gene sequence was obtained by aligning assembled genome of L. rohita, (NCBI BioProject ID: PRJNA437789), with the CTGF protein of zebrafish. Eight overlapping sets of forward and reverse primers from aligned region were designed for amplification of around 600 bp long successive overlapping fragments of CTGF gene in L. rohita. Assembly and annotation of overlapping fragments confirmed a complete 2421 bp long CTGF gene sequence with a full coding region that comprised of five exons between 308 and 1921 positions. This annotated CTGF gene sequence was submitted to GenBank (Acc. No. KY940466). Characterization of CTGF will be an initiative in identification of hypoxia response genes in L. rohita which may further help in understanding the mechanism of hypoxia tolerability in this species.

Host genetic factors are frequently ascribed to differential malaria outcomes as a by-product of evolutionary adaptation. To this respect, Tumor Necrosis factor alpha (TNF-α), a human cytokine, is known to be associated with malaria through its differential regulation in diverse malaria manifestations. Since diversity in differential malaria outcome is uncommon in every endemic settings, possible association of TNF-α and malaria is not commonly established. In order to check for association between the occurrence of Single Nucleotide Polymorphisms (SNPs) in the TNF-α gene with different malaria manifestations, we have sequenced a 4011 bp region constituting the promoter and the whole gene of human TNF-α in 61 patients [(16 cerebral plus severe (SCM), 21 severe (SM) and 24 uncomplicated (UM)] samples in a highly malaria endemic state (Odisha) of India. Multiple sequence alignment revealed presence of six SNPs (-1031 T > C, -863C > A, -857C > T, -308G > A, -806C > T, +787C > A), out of which the -806C > T and +787C > A are novel in malaria patients in general and the +787C > A was detected for the first time in humans. Although alleles due to six different SNPs segregate differentially in the three groups of malaria (SCM, SM and UM) in the present study, interestingly, for the -1031 T > C position, the frequency of individuals possessing the homozygous rare allele was higher in the SCM group with a higher number of heterozygotes in the UM group. The Tajima's D values considering all the SNPs in a defined group were positive and statistically insignificant conforming no evolutionary constraint. However, statistically significant deviation from expectation under Hardy-Weinberg equilibrium for -1031 T > C SNP in the UM group points towards the probable role of natural selection providing some kind of protection to malaria in Odisha, India., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Several studies have assessed the association between IL-17F and IL-10 promoter polymorphisms and asthma, but the results were conflicting. Furthermore, few studies have evaluated the association of cytokine polymorphisms with asthma and its clinical phenotypes., Objective: This study was conducted to evaluate the association of IL-10 (interleukin 10) and IL-17F (interleukin 17F) promoter polymorphisms (rs1800871, rs1800896 and rs1889570) with asthma and its clinical phenotypes including severity, atopic status, spirometric parameters, and response to treatment in south Indian population. A sub-study was conducted to assess cytokine levels in subjects with different gene variants., Methods: IL-10 and IL-17F polymorphisms were genotyped in 419 asthmatic patients and 393 controls using Mass ARRAY., Results: Our results showed an association between IL-10 SNPs and mild asthma. No association was found with any of three SNPs in moderate to severe asthma. Comparison of genotype distribution of IL-17F rs1887570 AA variant among atopic and non-atopic patients showed significant difference (p = 0.024). Correlation analysis of IL-10 and IL-17F SNPs to clinical variables showed a positive correlation between IL-17F rs1887570 AA and number of allergen sensitized (rs = 0.142, p = 0.004). Significant improvement in lung function was observed after 2 months of ICS (Inhaled corticosteroids) and LABA (long acting β2 agonist) treatment in all subjects with no statistically significant difference among SNPs variants. Cytokines levels were similar in different SNP variants., Conclusion: We observed an association between IL-10 rs1800871 and rs1800896 SNPs and mild asthma, as well as IL-17F rs1887570 AA variant and number of allergens sensitized.

The study aimed at characterization of buffalo β-casein gene and its promoter by PCR-SSCP analysis. Complete β-casein exon VII region analysis revealed two SSCP band patterns, with pattern-I representing predominant allele B (85%) present in homozygous (genotype BB) condition and pattern-II representing a rare allele A1 present in heterozygous condition (genotype A1B). Sequencing of two patterns revealed three nucleotide substitutions at codon 68, 151 and 193 of exon VII. The cDNA sequence of buffalo β-casein gene indicated three further nucleotide substitutions between allele A1 and B at codon 10, 39, and 41. Analysis of β-casein proximal promoter region (-350 upstream to +32) revealed four SSCP band patterns. These SSCP patterns corresponded to nucleotide substitutions at seven locations within 382 bp 5' UTR region of β-casein gene. Haplotype analysis suggested pattern-I of exon VII (wild type) was associated with three types of promoters and pattern-II of exon VII (rare type) corresponded to one exclusive type of promoter. The study suggested two haplotypes of exon VII and four haplotypes of promoter for buffalo β-casein., (© 2013 Elsevier B.V. All rights reserved.)