Next Article in Journal
The Effect of Tobacco Smoking Differs across Indices of DNA Methylation-Based Aging in an African American Sample: DNA Methylation-Based Indices of Smoking Capture These Effects
Next Article in Special Issue
Rolling-Circle Replication in Mitochondrial DNA Inheritance: Scientific Evidence and Significance from Yeast to Human Cells
Previous Article in Journal
Integrating Casein Complex SNPs Additive, Dominance and Epistatic Effects on Genetic Parameters and Breeding Values Estimation for Murciano-Granadina Goat Milk Yield and Components
Open AccessArticle

Pathogenic Effect of GDAP1 Gene Mutations in a Yeast Model

1
Neuromuscular Unit, Mossakowski Medical Research Centre Polish Academy of Sciences, 02-106 Warsaw, Poland
2
Institute of Biochemistry and Biophysics Polish Academy of Sciences, 02-106 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Genes 2020, 11(3), 310; https://doi.org/10.3390/genes11030310
Received: 19 February 2020 / Revised: 10 March 2020 / Accepted: 12 March 2020 / Published: 14 March 2020
(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)
The question of whether a newly identified sequence variant is truly a causative mutation is a central problem of modern clinical genetics. In the current era of massive sequencing, there is an urgent need to develop new tools for assessing the pathogenic effect of new sequence variants. In Charcot-Marie-Tooth disorders (CMT) with their extreme genetic heterogeneity and relatively homogenous clinical presentation, addressing the pathogenic effect of rare sequence variants within 80 CMT genes is extremely challenging. The presence of multiple rare sequence variants within a single CMT-affected patient makes selection for the strongest one, the truly causative mutation, a challenging issue. In the present study we propose a new yeast-based model to evaluate the pathogenic effect of rare sequence variants found within the one of the CMT-associated genes, GDAP1. In our approach, the wild-type and pathogenic variants of human GDAP1 gene were expressed in yeast. Then, a growth rate and mitochondrial morphology and function of GDAP1-expressing strains were studied. Also, the mutant GDAP1 proteins localization and functionality were assessed in yeast. We have shown, that GDAP1 was not only stably expressed but also functional in yeast cell, as it influenced morphology and function of mitochondria and altered the growth of a mutant yeast strain. What is more, the various GDAP1 pathogenic sequence variants caused the specific for them effect in the tests we performed. Thus, the proposed model is suitable for validating the pathogenic effect of known GDAP1 mutations and may be used for testing of unknown sequence variants found in CMT patients. View Full-Text
Keywords: yeast; mitochondria; Charcot-Marie-Tooth type 4 disease; GDAP1 gene; GDAP1 gene mutations yeast; mitochondria; Charcot-Marie-Tooth type 4 disease; GDAP1 gene; GDAP1 gene mutations
Show Figures

Figure 1

MDPI and ACS Style

Rzepnikowska, W.; Kaminska, J.; Kabzińska, D.; Kochański, A. Pathogenic Effect of GDAP1 Gene Mutations in a Yeast Model. Genes 2020, 11, 310.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop