Related Experiment Video

Updated: May 11, 2026

A Web-Based Workflow for Selecting Gene- and Tissue-Specific Enhancers
08:12

A Web-Based Workflow for Selecting Gene- and Tissue-Specific Enhancers

Published on: July 18, 2025

Two novel and functional DNA sequence variants within an upstream enhancer of the human NKX2-5 gene in ventricular

Wenhui Huang1, Haihong Meng, Yuangang Qiao

  • 1Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.

Gene
|May 7, 2013
PubMed

Insights

Genetic variants in an NKX2-5 gene enhancer may contribute to congenital heart defects like ventricular septal defect (VSD). This finding could inform new therapies for adult congenital heart disease (CHD).

Area of Science:

  • Cardiovascular Genetics
  • Developmental Biology
  • Molecular Cardiology

Background:

  • Congenital heart disease (CHD) has high mortality due to late complications, often linked to unknown genetic factors.
  • The NKX2-5 gene is crucial for heart development and function; mutations are associated with various CHDs, including ventricular septal defect (VSD).
  • NKX2-5 acts as a dosage-sensitive regulator, suggesting altered gene expression levels may influence CHD development via gene regulatory networks.

Purpose of the Study:

  • To genetically and functionally analyze an upstream enhancer of the NKX2-5 gene in patients with VSD.
  • To investigate the role of DNA sequence variants (DSVs) in this enhancer in the development of VSD.

Main Methods:

  • Genomic DNA analysis of large cohorts of VSD patients (n=340) and controls (n=347).
  • Identification and characterization of novel heterozygous DNA sequence variants (DSVs) in the NKX2-5 upstream enhancer.
  • Functional assessment of identified DSVs using enhancer activity assays.

Main Results:

  • Two novel heterozygous DSVs (g.17483576C>G and g.17483564C>T) were identified in three VSD patients but not in controls.
  • These two DSVs significantly reduced the enhancer activity (P<0.01).
  • A third novel heterozygous DSV (g.17483557Ins) was found at similar frequencies in both VSD patients and controls (P>0.05).

Conclusions:

  • The identified DSVs within the NKX2-5 upstream enhancer may contribute to a subset of VSD cases.
  • These genetic findings highlight the importance of regulatory elements in CHD pathogenesis.
  • Understanding genetic causes of CHD can guide the development of novel therapeutic strategies for adult patients.

More Related Videos

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay (EMSA) and DNA-affinity Precipitation Assay (DAPA)11:35

Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay (EMSA) and DNA-affinity Precipitation Assay (DAPA)

Published on: August 21, 2016

Related Concept Videos

Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...