Prediction of structural consequences for disease causing variants in C21orf2 protein using computational approaches

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis (ALS), a progressive motor-neurone disease, affects individuals usually aged between 50 and 70 years. C21orf2, recently identified as the new ALS susceptibility gene, harbours rare missense mutations that cause this fatal disease. We used bioinformatics and molecular modelling approaches to study specific ALS-associated mutations in C21orf2. Both native and mutant structures of the protein obtained from homology modelling were analysed in detail to gain insights into the potential impact of these mutations on the protein structure and its function. Our analyses reveal that more than 75% of the mutations are likely to be deleterious. These effects seem to carry through to mouse C21orf2 as well, indicating that mouse would make a viable animal model to study this ALS gene in detail.

LanguageEnglish
Pages1-32
Number of pages32
JournalJournal of Biomolecular Structure & Dynamics
Early online date17 Jan 2018
DOIs
StatusE-pub ahead of print - 17 Jan 2018

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Amyotrophic Lateral Sclerosis
Mutation
Proteins
Motor Neuron Disease
Missense Mutation
Mutant Proteins
Computational Biology
Genes
Animal Models

Keywords

  • Journal Article

Cite this

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title = "Prediction of structural consequences for disease causing variants in C21orf2 protein using computational approaches",
abstract = "Amyotrophic lateral sclerosis (ALS), a progressive motor-neurone disease, affects individuals usually aged between 50 and 70 years. C21orf2, recently identified as the new ALS susceptibility gene, harbours rare missense mutations that cause this fatal disease. We used bioinformatics and molecular modelling approaches to study specific ALS-associated mutations in C21orf2. Both native and mutant structures of the protein obtained from homology modelling were analysed in detail to gain insights into the potential impact of these mutations on the protein structure and its function. Our analyses reveal that more than 75{\%} of the mutations are likely to be deleterious. These effects seem to carry through to mouse C21orf2 as well, indicating that mouse would make a viable animal model to study this ALS gene in detail.",
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author = "Shalini Iyer and Acharya, {K Ravi} and Vasanta Subramanian",
year = "2018",
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AU - Iyer,Shalini

AU - Acharya,K Ravi

AU - Subramanian,Vasanta

PY - 2018/1/17

Y1 - 2018/1/17

N2 - Amyotrophic lateral sclerosis (ALS), a progressive motor-neurone disease, affects individuals usually aged between 50 and 70 years. C21orf2, recently identified as the new ALS susceptibility gene, harbours rare missense mutations that cause this fatal disease. We used bioinformatics and molecular modelling approaches to study specific ALS-associated mutations in C21orf2. Both native and mutant structures of the protein obtained from homology modelling were analysed in detail to gain insights into the potential impact of these mutations on the protein structure and its function. Our analyses reveal that more than 75% of the mutations are likely to be deleterious. These effects seem to carry through to mouse C21orf2 as well, indicating that mouse would make a viable animal model to study this ALS gene in detail.

AB - Amyotrophic lateral sclerosis (ALS), a progressive motor-neurone disease, affects individuals usually aged between 50 and 70 years. C21orf2, recently identified as the new ALS susceptibility gene, harbours rare missense mutations that cause this fatal disease. We used bioinformatics and molecular modelling approaches to study specific ALS-associated mutations in C21orf2. Both native and mutant structures of the protein obtained from homology modelling were analysed in detail to gain insights into the potential impact of these mutations on the protein structure and its function. Our analyses reveal that more than 75% of the mutations are likely to be deleterious. These effects seem to carry through to mouse C21orf2 as well, indicating that mouse would make a viable animal model to study this ALS gene in detail.

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