MtSNPscore: a combined evidence approach for assessing cumulative impact of mitochondrial variations in disease
Anshu Bhardwaj,Mitali Mukerji,Shipra Sharma,Jinny A. Paul,Chaitanya S. Gokhale,Achal Kumar Srivastava,Shrish Tiwari +6 more
- Vol. 10, Iss: 8, pp 1-12
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TLDR
The MtSNPscore method has the most comprehensive set of parameters to assess mtDNA variations and overcomes the undesired bias generated as a result of better-studied diseases and genes.Abstract:
Background
Human mitochondrial DNA (mtDNA) variations have been implicated in a broad spectrum of diseases. With over 3000 mtDNA variations reported across databases, establishing pathogenicity of variations in mtDNA is a major challenge. We have designed and developed a comprehensive weighted scoring system (MtSNPscore) for identification of mtDNA variations that can impact pathogenicity and would likely be associated with disease. The criteria for pathogenicity include information available in the literature, predictions made by various in silico tools and frequency of variation in normal and patient datasets. The scoring scheme also assigns scores to patients and normal individuals to estimate the cumulative impact of variations. The method has been implemented in an automated pipeline and has been tested on Indian ataxia dataset (92 individuals), sequenced in this study, and other publicly available mtSNP dataset comprising of 576 mitochondrial genomes of Japanese individuals from six different groups, namely, patients with Parkinson's disease, patients with Alzheimer's disease, young obese males, young non-obese males, and type-2 diabetes patients with or without severe vascular involvement. MtSNPscore, for analysis can extract information from variation data or from mitochondrial DNA sequences. It has a web-interface http://bioinformatics.ccmb.res.in/cgi-bin/snpscore/Mtsnpscore.pl that provides flexibility to update/modify the parameters for estimating pathogenicity.read more
Citations
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MitoTool: A web server for the analysis and retrieval of human mitochondrial DNA sequence variations
Long Fan,Long Fan,Yong-Gang Yao +2 more
TL;DR: The MitoTool, a web-based bioinformatics platform, is designed for deciphering human mitochondrial DNA data in batch mode and offers an integrated database for retrieving five types of mitochondrion-related information.
Journal ArticleDOI
Phylomedicine: an evolutionary telescope to explore and diagnose the universe of disease mutations
TL;DR: It is concluded that the patterns of long-term evolutionary conservation and permissible sequence divergence are essential and instructive modalities for functional assessment of human genetic variations.
Journal ArticleDOI
Identification of the direct regulon of NtcA during early acclimation to nitrogen starvation in the cyanobacterium Synechocystis sp. PCC 6803.
Joaquín Giner-Lamia,Joaquín Giner-Lamia,Rocío Robles-Rengel,Miguel A. Hernández-Prieto,Miguel A. Hernández-Prieto,M. Isabel Muro-Pastor,Francisco J. Florencio,Matthias E. Futschik,Matthias E. Futschik +8 more
TL;DR: It is suggested that the indicated poised state of NtcA enables a more differentiated response to nitrogen limitation and can be advantageous in native habitats of Synechocystis.
Journal ArticleDOI
Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation.
Elizabeth M. McCormick,Marie T. Lott,Matthew C. Dulik,Matthew C. Dulik,Lishuang Shen,Marcella Attimonelli,Ornella Vitale,Amel Karaa,Renkui Bai,Daniel E. Pineda-Alvarez,Larry N. Singh,Christine M. Stanley,Stacey Wong,Anshu Bhardwaj,Daria Merkurjev,Rong Mao,Rong Mao,Neal Sondheimer,Shiping Zhang,Vincent Procaccio,Douglas C. Wallace,Douglas C. Wallace,Xiaowu Gai,Xiaowu Gai,Marni J. Falk,Marni J. Falk +25 more
TL;DR: This group reviewed the 2015 American College of Medical Genetics and Association of Molecular Pathology standards and guidelines that are widely used for clinical interpretation of DNA sequence variants and provided further specifications for additional and specific guidance related to mtDNA variant classification.
Journal ArticleDOI
Human genomic disease variants: A neutral evolutionary explanation
Joel T. Dudley,Yuseob Kim,Li Liu,Glenn J. Markov,Kristyn Gerold,Rong Chen,Atul J. Butte,Sudhir Kumar +7 more
TL;DR: It is suggested that a majority of disease variants in modern populations will have neutral evolutionary origins, with a relatively smaller fraction exhibiting adaptive evolutionary origins (previously adaptive).
References
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Journal ArticleDOI
A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine
TL;DR: The mitochondria provide a direct link between the authors' environment and their genes and the mtDNA variants that permitted their forbears to energetically adapt to their ancestral homes are influencing their health today.
Journal ArticleDOI
Mitochondrial diseases in man and mouse.
TL;DR: The essential role of mitochondrial oxidative phosphorylation in cellular energy production, the generation of reactive oxygen species, and the initiation of apoptosis has suggested a number of novel mechanisms for mitochondrial pathology.
Journal ArticleDOI
Human non‐synonymous SNPs: server and survey
TL;DR: A World Wide Web server is presented to predict the effect of an nsSNP on protein structure and function and the dependence of selective pressure on the structural and functional properties of proteins is studied.
Journal ArticleDOI
tRNA punctuation model of RNA processing in human mitochondria
TL;DR: It is proposed that the H strand is transcribed into a single polycistronic RNA molecule, which is processed later into mature species by precise endonucleolytic cleavages which occur, in most cases, immediately before and after a tRNA sequence.