Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Clinically Relevant Drug Product Specifications: Methods of Establishment01:29

Clinically Relevant Drug Product Specifications: Methods of Establishment

222
Product specifications define the acceptable quality of a pharmaceutical product by ensuring identity, purity, potency, and strength. These specifications serve as benchmarks during development, manufacturing, and post-approval quality control. Clinically relevant specifications are particularly important because they directly relate to a drug's safety and efficacy in clinical use.Dissolution studies are critical biopharmaceutic tools that link in vitro behavior to in vivo performance. They...
222
Histone Variants at the Centromere02:30

Histone Variants at the Centromere

5.1K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
5.1K
Transcription01:10

Transcription

156.8K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
156.8K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

11.0K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
Master Transcription Regulators02:23

Master Transcription Regulators

7.8K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.8K
Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

12.8K
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
12.8K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Harmonizing standards and resources for the medical genome.

Nature·2026
Same author

Automated reanalysis of genomic data for rare disease diagnostics at scale.

Nature medicine·2026
Same author

Long-term Penetrance of Disease Variants in Genes Prioritized for Genomic Newborn Screening: Evidence from Adult Biobanks.

medRxiv : the preprint server for health sciences·2026
Same author

Points to consider for the reporting of variants of uncertain significance in germline genetic and genomic testing: A statement of the American College of Medical Genetics and Genomics (ACMG).

Genetics in medicine : official journal of the American College of Medical Genetics·2026
Same author

Building an Interoperable Rare Disease Multi-omic Resource: The GREGoR Data Model and Dataset.

bioRxiv : the preprint server for biology·2026
Same author

A comparative survey of functional evidence use in hearing and vision loss genetics.

Communications medicine·2026

Related Experiment Video

Updated: Feb 6, 2026

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
14:06

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER

Published on: June 23, 2012

15.7K

Curating Clinically Relevant Transcripts for the Interpretation of Sequence Variants.

Marina T DiStefano1, Sarah E Hemphill1, Brandon J Cushman1

  • 1Laboratory for Molecular Medicine, Partners Healthcare Personalized Medicine, Cambridge, Massachusetts.

The Journal of Molecular Diagnostics : JMD
|August 11, 2018
PubMed
Summary

Accurate variant interpretation for hearing loss relies on identifying the correct gene transcripts. This study developed a strategy to designate primary transcripts and classify exons, improving clinical variant analysis.

More Related Videos

A Model to Simulate Clinically Relevant Hypoxia in Humans
09:54

A Model to Simulate Clinically Relevant Hypoxia in Humans

Published on: December 22, 2016

9.4K
Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

15.5K

Related Experiment Videos

Last Updated: Feb 6, 2026

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
14:06

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER

Published on: June 23, 2012

15.7K
A Model to Simulate Clinically Relevant Hypoxia in Humans
09:54

A Model to Simulate Clinically Relevant Hypoxia in Humans

Published on: December 22, 2016

9.4K
Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

15.5K

Area of Science:

  • Genetics
  • Bioinformatics
  • Molecular Biology

Background:

  • Accurate genetic variant interpretation is crucial for diagnosing hereditary conditions like hearing loss.
  • The selection of biologically relevant transcripts is fundamental for precise variant annotation.
  • Existing annotation strategies may not adequately address the complexity of multiple transcripts per gene.

Purpose of the Study:

  • To develop and apply a systematic strategy for designating primary transcripts for hearing loss-associated genes.
  • To classify exons based on clinical significance and technical challenges in variant calling.
  • To improve the accuracy of clinical variant interpretation in genetic testing.

Main Methods:

  • A systematic strategy was developed to designate primary transcripts for 109 hearing loss-associated genes, categorized by transcript complexity.
  • Transcript curation involved literature review and Genotype-Tissue Expression (GTEx) Project data.
  • Exon classification utilized variant data from public databases (gnomAD, ClinVar, HGMD) and next-generation sequencing quality metrics.

Main Results:

  • The study categorized 109 hearing loss genes into single-transcript, sufficient-transcript, and unique-exon categories.
  • Approximately 6% of all exons, including those with 124 reported disease-causing variants, were classified as of uncertain significance.
  • 43 technically challenging exons across 20 genes were identified due to inadequate coverage or homology issues, potentially causing false variant calls.

Conclusions:

  • Transcript analysis is critical for accurate clinical variant interpretation in genetic testing.
  • A standardized approach to transcript designation and exon classification enhances diagnostic precision.
  • Identifying technically challenging exons can mitigate errors in next-generation sequencing-based variant detection.