scholarly journals MaveDB v2: a curated community database with over three million variant effects from multiplexed functional assays

2021 ◽  
Author(s):  
Alan F Rubin ◽  
Joseph K Min ◽  
Nathan J Rollins ◽  
Estelle Y Da ◽  
Daniel Esposito ◽  
...  
Keyword(s):  
Large Fraction ◽  
Single Nucleotide Variant ◽  
Central Problem ◽  
Regulatory Sequence ◽  
Single Nucleotide ◽  
Data Submission ◽  
Functional Assays ◽  
Dna Variants ◽  
Variant Effect

A central problem in genomics is understanding the effect of individual DNA variants. Multiplexed Assays of Variant Effect (MAVEs) can help address this challenge by measuring all possible single nucleotide variant effects in a gene or regulatory sequence simultaneously. Here we describe MaveDB v2, which has become the database of record for MAVEs. MaveDB now contains a large fraction of published studies, comprising over two hundred datasets and three million variant effect measurements. We created tools and APIs to streamline data submission and access, transforming MaveDB into a hub for the analysis and dissemination of these impactful datasets.

scholarly journals A single nucleotide variant in the promoter region of the CCR5 gene increases susceptibility to arthritis encephalitis virus in goats

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Silvia Colussi ◽  
Rosanna Desiato ◽  
Chiara Beltramo ◽  
Simone Peletto ◽  
Paola Modesto ◽  
...  
Keyword(s):  
Promoter Region ◽  
Single Nucleotide Variant ◽  
Encephalitis Virus ◽  
Ccr5 Gene ◽  
Single Nucleotide

scholarly journals Nonsynonymous single nucleotide polymorphisms of NHE3 differentially decrease NHE3 transporter activity

2015 ◽  
Vol 308 (9) ◽  
pp. C758-C766 ◽  
Author(s):  
Xinjun Cindy Zhu ◽  
Rafiquel Sarker ◽  
John R. Horton ◽  
Molee Chakraborty ◽  
Tian-E Chen ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Large Fraction ◽  
Regulatory Protein ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide ◽  
Mutant Proteins ◽  
Homologous Protein ◽  
Genetic Abnormalities ◽  
The Impact

Genetic determinants appear to play a role in susceptibility to chronic diarrhea, but the genetic abnormalities involved have only been identified in a few conditions. The Na+/H+ exchanger 3 (NHE3) accounts for a large fraction of physiologic intestinal Na+ absorption. It is highly regulated through effects on its intracellular COOH-terminal regulatory domain. The impact of genetic variation in the NHE3 gene, such as single nucleotide polymorphisms (SNPs), on transporter activity remains unexplored. From a total of 458 SNPs identified in the entire NHE3 gene, we identified three nonsynonymous mutations (R474Q, V567M, and R799C), which were all in the protein's intracellular COOH-terminal domain. Here we evaluated whether these SNPs affect NHE3 activity by expressing them in a mammalian cell line that is null for all plasma membrane NHEs. These variants significantly reduced basal NHE3 transporter activity through a reduction in intrinsic NHE3 function in variant R474Q, abnormal trafficking in variant V567M, or defects in both intrinsic NHE3 function and trafficking in variant R799C. In addition, variants NHE3 R474Q and R799C failed to respond to acute dexamethasone stimulation, suggesting cells with these mutant proteins might be defective in NHE3 function during postprandial stimulation and perhaps under stressful conditions. Finally, variant R474Q was shown to exhibit an aberrant interaction with calcineurin B homologous protein (CHP), an NHE3 regulatory protein required for basal NHE3 activity. Taken together, these results demonstrate decreased transport activity in three SNPs of NHE3 and provide mechanistic insight into how these SNPs impact NHE3 function.

Beyond the single nucleotide variant in epilepsy genetics

2014 ◽  
Vol 10 (9) ◽  
pp. 490-491 ◽  
Author(s):  
Ingrid E. Scheffer ◽  
Heather C. Mefford
Keyword(s):  
Single Nucleotide Variant ◽  
Single Nucleotide

Combining cooperativity with sequestration: a novel strategy for discrimination of single nucleotide variants

2018 ◽  
Vol 54 (26) ◽  
pp. 3223-3226 ◽  
Author(s):  
Shichao Hu ◽  
Na Li ◽  
Feng Liu
Keyword(s):  
Single Nucleotide Variant ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Discrimination Ability ◽  
Novel Strategy

We present a novel single nucleotide variant discrimination strategy combining cooperativity with sequestration to significantly improve the discrimination ability.

scholarly journals MaveRegistry: a collaboration platform for multiplexed assays of variant effect

2020 ◽  
Author(s):  
Da Kuang ◽  
Jochen Weile ◽  
Nishka Kishore ◽  
Alan F. Rubin ◽  
Stanley Fields ◽  
...  
Keyword(s):  
Amino Acid ◽  
International Community ◽  
Human Variation ◽  
Single Nucleotide ◽  
Clinical Interpretation ◽  
Link Type ◽  
Variant Effect ◽  
Genomic Regions ◽  
Amino Acid Variants

AbstractSummaryMultiplexed assays of variant effect (MAVEs) are capable of experimentally testing all possible single nucleotide or amino acid variants in selected genomic regions, generating ‘variant effect maps’, which provide biochemical insight and functional evidence to enable more rapid and accurate clinical interpretation of human variation. Because the international community applying MAVE approaches is growing rapidly, we developed the online MaveRegistry platform to catalyze collaboration, reduce redundant efforts, allow stakeholders to nominate targets, and enable tracking and sharing of progress on ongoing MAVE projects.Availability and implementationhttps://[email protected]

Sign in / Sign up

Export Citation Format

Share Document