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

Modern Molecular Taxonomy01:29

Modern Molecular Taxonomy

318
Advancements in molecular biology have revolutionized the identification and characterization of bacteria, with multiple methods leveraging DNA sequencing for enhanced precision. As sequencing technologies improve and costs decline, these approaches are increasingly used in clinical, environmental, and evolutionary studies.Multilocus Sequence Typing (MLST) examines several housekeeping genes, essential chromosomal genes encoding cellular functions, to distinguish strains. Approximately...
318
Classification of Leukocytes01:30

Classification of Leukocytes

4.0K
Leukocytes are classified into two groups based on the presence or absence of cytoplasmic granules. Granular leukocytes, which contain granules, belong to the myeloid lineage and are divided into three subtypes: neutrophils, eosinophils, and basophils. These cells are roughly spherical and characterized by the granules in their cytoplasm.
Neutrophils are the most abundant type of granular leukocytes, comprising 50-70% of all leukocytes. They feature small, evenly distributed granules and a...
4.0K
Leaky Scanning02:28

Leaky Scanning

5.3K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.3K

You might also read

Related Articles

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

Sort by
Same author

Lynch Syndrome: An Update of Underlying Molecular Mechanisms, Phenotypes and Methods to Classify Variants of Uncertain Significance.

Biomedicines·2026
Same author

Tracing the early dispersal of reindeer in southern Sweden: Chronology, habitat, and human interaction (<i>c</i>. 12,000-7000 BCE).

The Holocene·2026
Same author

The ligand preference of LRP1 is regulated by O-glycans.

Science advances·2026
Same author

Familial hypercholesterolaemia in children and adolescents: a European Atherosclerosis Society consensus statement.

European heart journal·2026
Same author

Global survey of genetic testing methods for familial hypercholesterolemia. A study and recommendations from the EAS FHSC registry.

European journal of preventive cardiology·2026
Same author

Dissecting the impact of SHC-1 inhibitors in enhancing the plasma membrane abundance of the CFTR channel across epithelial cell models.

Biochemical and biophysical research communications·2026

Related Experiment Video

Updated: Nov 1, 2025

Functional Characterization of Endogenously Expressed Human RYR1 Variants
07:59

Functional Characterization of Endogenously Expressed Human RYR1 Variants

Published on: June 9, 2021

2.8K

LDLR variants functional characterization: Contribution to variant classification.

Ana Catarina Alves1, Sílvia Azevedo2, Asier Benito-Vicente3

  • 1Unidade de I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; BioISI - Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal.

Atherosclerosis
|June 24, 2021
PubMed
Summary
This summary is machine-generated.

Functional studies on 13 LDLR variants improved Familial Hypercholesterolemia (FH) diagnosis. Seven variants were shown to impair LDLR function, aiding in definitive FH diagnoses for 55 patients.

Keywords:
Familial hypercholesterolemiaFunctional studiesLDLRMolecular diagnosisVariants

More Related Videos

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.1K
Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
08:04

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

722

Related Experiment Videos

Last Updated: Nov 1, 2025

Functional Characterization of Endogenously Expressed Human RYR1 Variants
07:59

Functional Characterization of Endogenously Expressed Human RYR1 Variants

Published on: June 9, 2021

2.8K
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.1K
Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
08:04

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

722

Area of Science:

  • Genetics
  • Biochemistry
  • Cardiovascular Medicine

Background:

  • Familial hypercholesterolemia (FH) is a genetic lipid disorder increasing cardiovascular risk.
  • LDLR gene mutations cause 90% of FH cases, but many variants lack functional data.
  • The Portuguese Familial Hypercholesterolemia Study identified 142 LDLR alterations, with 44 uncharacterized.

Purpose of the Study:

  • To functionally characterize 13 LDLR missense variants identified in Portugal and globally.
  • To provide evidence for accurate variant classification and FH diagnosis.
  • To increase the number of clinically actionable genetic variants for FH.

Main Methods:

  • Generated and expressed LDLR mutants in CHO-ldlA7 cells.
  • Assessed LDLR function using flow cytometry and Western blot to measure cell surface expression, LDL binding, and uptake.
  • Site-directed mutagenesis was used to create specific LDLR variants.

Main Results:

  • Seven of the 13 studied LDLR variants demonstrated impaired function (expression, binding, or uptake <60%).
  • Specific variants affecting LDLR function include p.(Cys184Tyr), p.(Gly207_Ser213del), p.(His211Asp), p.(Asp221Tyr), p.(Glu288Lys), p.(Gly592Glu), and p.(Asp601Val).
  • The remaining six variants showed no significant impact on LDLR function.

Conclusions:

  • Functional characterization reclassified 7 variants of unknown significance and upgraded 3 likely pathogenic to pathogenic.
  • These studies enabled definitive FH diagnoses for an additional 55 patients in Portugal.
  • Functional studies are crucial for accurate variant classification and clinical actionability in FH.