Related Experiment Video
Updated: Jul 12, 2025
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
[Genetic analysis of two families with Short-rib thoracic dysplasia type 3]
1Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Medical Genetics, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. xiulizhao@ibms.pumc.edu.cn.
Objective:
To explore the pathogenic variants and clinical classification of two fetuses with Short-rib thoracic dysplasia with or without polydactyly (SRTD).
Methods:
With informed consent obtained, the phenotypic characteristics of the fetuses were comprehensively examined, and genomic DNA was extracted from fetal skin tissue and peripheral blood samples of the parents with conventional phenol-chloroform method. Whole exome sequencing (WES) was carried out on both fetuses, and the candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was analyzed using bioinformatic software VarCards, and the impact of the variants on the protein structure was predicted with Swiss-Pdb-viewer.
Results:
Both fetuses were found to harbor compound heterozygous variants of the DYNC2H1 gene, including c.515C>A (p.Pro172Gln) and c.5983G>A (p.Ala1995Thr) in fetus 1, and c.5920G>T (pGly1974) and c.9908T>C (p.He3303Thr) in fetus 2. The parents of both fetuses were heterozygous carriers.
Conclusion:
The compound heterozygous variants of the DYNC2H1 gene probably underlay the SRTD3 in the two fetuses.
Related Concept Videos
01:43Incomplete Dominance
01:35Pedigree Analysis
01:09Epistasis Analysis
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
02:59Animal Mitochondrial Genetics