Biomedical subjects

Vineet K Sharma

Publications and source records attributed to Vineet K Sharma.

5 recordsLinked to original sources

PubMed2006

Expoldb: expression linked polymorphism database with inbuilt tools for analysis of expression and simple repeats.

BACKGROUND: Quantitative variation in gene expression has been proposed to underlie phenotypic variation among human individuals. A facilitating step towards understanding the basis for gene expression variability is associating genome wide transcription patterns with potential cis modifiers of gene expression. DESCRIPTION: EXPOLDB, a novel Database, is a new effort addressing this need by providing information on gene expression levels variability across individuals, as well as the presence and features of potentially polymorphic (TG/CA)n repeats. EXPOLDB thus enables associating transcription levels with the presence and length of (TG/CA)n repeats. One of the unique features of this database is the display of expression data for 5 pairs of monozygotic twins, which allows identification of genes whose variability in expression, are influenced by non-genetic factors including environment. In addition to queries by gene name, EXPOLDB allows for queries by a pathway name. Users can also upload their list of HGNC (HUGO (The Human Genome Organisation) Gene Nomenclature Committee) symbols for interrogating expression patterns. The online application 'SimRep' can be used to find simple repeats in a given nucleotide sequence. To help illustrate primary applications, case examples of Housekeeping genes and the RUNX gene family, as well as one example of glycolytic pathway genes are provided. CONCLUSION: The uniqueness of EXPOLDB is in facilitating the association of genome wide transcription variations with the presence and type of polymorphic repeats while offering the feature for identifying genes whose expression variability are influenced by non genetic factors including environment. In addition, the database allows comprehensive querying including functional information on biochemical pathways of the human genes. EXPOLDB can be accessed at http://expoldb.igib.res.in/expol.

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PubMed2005

(TG/CA)n repeats in human gene families: abundance and selective patterns of distribution according to function and gene length.

BACKGROUND: Creation of human gene families was facilitated significantly by gene duplication and diversification. The (TG/CA)n repeats exhibit length variability, display genome-wide distribution, and are abundant in the human genome. Accumulation of evidences for their multiple functional roles including regulation of transcription and stimulation of recombination and splicing elect them as functional elements. Here, we report analysis of the distribution of (TG/CA)n repeats in human gene families. RESULTS: The 1,317 human gene families were classified into six functional classes. Distribution of (TG/CA)n repeats were analyzed both from a global perspective and from a stratified perspective based on their biological properties. The number of genes with repeats decreased with increasing repeat length and several genes (53%) had repeats of multiple types in various combinations. Repeats were positively associated with the class of Signaling and communication whereas, they were negatively associated with the classes of Immune and related functions and of Information. The proportion of genes with (TG/CA)n repeats in each class was proportional to the corresponding average gene length. The repeat distribution pattern in large gene families generally mirrored the global distribution pattern but differed particularly for Collagen gene family, which was rich in repeats. The position and flanking sequences of the repeats of Collagen genes showed high conservation in the Chimpanzee genome. However the majority of these repeats displayed length polymorphism. CONCLUSION: Positive association of repeats with genes of Signaling and communication points to their role in modulation of transcription. Negative association of repeats in genes of Information relates to the smaller gene length, higher expression and fundamental role in cellular physiology. In genes of Immune and related functions negative association of repeats perhaps relates to the smaller gene length and the directional nature of the recombinogenic processes to generate immune diversity. Thus, multiple factors including gene length, function and directionality of recombinogenic processes steered the observed distribution of (TG/CA)n repeats. Furthermore, the distribution of repeat patterns is consistent with the current model that long repeats tend to contract more than expand whereas, the reverse dynamics operates in short repeats.

Animals↗

PubMed2005

Assessing natural variations in gene expression in humans by comparing with monozygotic twins using microarrays.

Quantitative variation in gene expression in humans is the outcome of various factors, including differences in genetic background, gender, age, and environment. However, the extent of the influence of these factors on gene expression is not clear. We attempted to address this issue by carrying out gene expression profiling in blood leukocytes with 13 individuals (including 5 pairs of monozygotic twins) on 10,000 genes using HG-U95Av2 oligonucleotide microarrays. The proportion of differentially expressed genes between monozygotic twins was low (up to 1.76%). Most of the variations belonged to the least variable category. These genes, exhibiting "random variations," did not show clear preference to any functional class, although "signaling and communication" and "immune and related functions" generally topped the list. The extent of variation in gene expression increased in comparisons between unrelated individuals (up to 14.13%). Most of the genes (89%) exhibiting random variations in twins also varied in expression in unrelated individuals. As with twins, signaling and communication topped the list, and substantial variations were observed in all three categories: least variable, moderately variable, and most variable. An important outcome of this study was that the housekeeping genes were nearly insensitive to random variations but appeared to be more susceptible to genetic differences. However, the highly expressed housekeeping genes exhibited low variation and appeared to be insensitive to all known factors. Gene expression profiling in monozygotic twins can provide useful data for the assessment of natural variation in gene expression in humans.

Adult↗

PubMed2004

ArrayD: a general purpose software for microarray design.

BACKGROUND: Microarray is a high-throughput technology to study expression of thousands of genes in parallel. A critical aspect of microarray production is the design aimed at space optimization while maximizing the number of gene probes and their replicates to be spotted. RESULTS: We have developed a software called 'ArrayD' that offers various alternative design solutions for an array given a set of user requirements. The user feeds the following inputs: type of source plates to be used, number of gene probes to be printed, number of replicates and number of pins to be used for printing. The solutions are stored in a text file. The choice of a design solution to be used will be governed by the spotting chemistry to be used and the accuracy of the robot. CONCLUSIONS: ArrayD is a software for standard cartesian robots. The software aids users in preparing a judicious and elegant design. ArrayD is universally applicable and is available at http://www.igib.res.in/scientists/arrayd/arrayd.html.

Computational Biology↗

PubMed2003

(TG:CA)(n) repeats in human housekeeping genes.

The unravelling of human genome sequence gives a new opportunity to investigate the role of repetitive sequences in gene regulation. Among the various types of repetitive sequences, the dinucleotide (TG:CA)(n) repeats are one of the most abundant in human genome and exhibit polymorphism. Early on, it was observed that the (TG:CA)(n) repeats could modulate gene expression and has the propensity to undergo conformational transitions in in vivo conditions. Recent reports describe the role of polymorphic (TG:CA)(n) repeats in gene regulation in several genes. In this work, we have analysed the distribution of (TG:CA)(n) (n >or= 6) repeats in human 'housekeeping genes' on which recently released Gene Chip data is available. Our results indicate that (i). The number of short intragenic (TG:CA)(n) repeats is significantly higher than the number of long repeats (ii). the proportion of genes with (TG:CA)(n) repeats (n >or= 12 units) had lower mean expression levels compared to those without these repeats, (iii). the genes belonging to the functional class of 'signalling and communication' had a positive association with repeats in contrast to the genes belonging to the 'information' class that were negatively associated with repeats.

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