Related Experiment Video
Updated: Apr 26, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Characterization of nodal/TGF-lefty signaling pathway gene variants for possible roles in congenital heart diseases
Xia Deng1, Jing Zhou2, Fei-Feng Li1
1Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
Background:
Nodal/TGF-Lefty signaling pathway has important effects at early stages of differentiation of human embryonic stem cells in directing them to differentiate into different embryonic lineages. LEFTY, one of transforming growth factors in the Nodal/TGF-Lefty signaling pathway, plays an important role in the development of heart. The aim of this work was to find evidence on whether Lefty variations are associated with congenital heart diseases (CHD).
Methods:
We sequenced the Lefty gene for 230 Chinese Han CHD patients and evaluated SNPs rs2295418, rs360057 and g.G169A, which are located within the translated regions of the genes. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the population was carried out using online software OEGE, and multiple-sequence alignments of LEFTY proteins were carried out using the Vector NTI software.
Results:
Two heterozygous variants in Lefty1 gene, g.G169A and g.A1035C, and one heterozygous variant in Lefty2 gene, g.C925A, were identified. Statistical analyses showed that the rs2295418 (g.C925A) variant in Lefty2 gene was obviously associated with the risk of CHD (P value = 0.016<0.05). The genotype frequency of rs360057 (g.A1035C) variant in Lefty1 gene was associated with the risk of CHD (P value = 0.007<0.05), but the allele frequency was not (P value = 0.317>0.05).
Conclusions:
The SNP rs2295418 in the Lefty2 gene is associated with CHD in Chinese Han populations.
Related Concept Videos
TGF - β Signaling Pathway
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
Principles of Pharmacogenetics: Types of Genetic Variants
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pulmonary Hypertension: Classification and Pathogenesis
There are various classifications for PH, each relating to different underlying causes and also...

