Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.1
3.5
Journals
Genes
Special Issues
Genomic Mosaicism in Human Development and Diseases
share announcement

Genomic Mosaicism in Human Development and Diseases

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: 15 June 2024 | Viewed by 2365

Special Issue Editor

Dr. Xiaoxu Yang

E-Mail Website
Guest Editor
Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
Interests: genomic mosaicism; diseases; cancer

Special Issue Information

Dear Colleagues,

Genomic mosaicism defines the phenomenon that different tissues and organs from the same individual present different genomic sequences. Mosaicism is a result of postzygotic mutations occurring during embryonic development, tissue self-renewal, environmental toxicity, aging, and disease. The failure to repair these mutations will leave them in the genome throughout one’s lifespan, and the mutations will be inherited by all the carrier’s daughter cells.

On the one hand, neutral or near-neutral genomic mosaic mutations can serve as recorders of human embryonic development. They are naturally barcoding the developmental cell clones, helping researchers to reconstruct lineage distribution patterns of early embryonic development.

On the other hand, emerging evidence has demonstrated that mosaic mutations are important genetic origins of disease. Cancer driver mutations have already shown to be detectable on adjacent tissues that are apparently normal. Apart from skin and skeletal disorders where mosaic mutations are already a known cause, developmental disorders and autoimmune disorders have also been demonstrated to be caused by mosaic mutations.

In this Special Issue, submissions on the following, but not limited to, topics are welcome:

    ● Mosaicism in human development;

    ● Somatic mosaicism that directly causes human disorders;

    ● Pre-disease mosaic mutation burdens for different disorders;

    ● Methodologies for mosaic studies.

Dr. Xiaoxu Yang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mosaicism
  • mutations
  • development
  • disorder
  • cancer

Published Papers (2 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

17 pages, 2637 KiB  
Article
Exploring the Micro-Mosaic Landscape of FGFR3 Mutations in the Ageing Male Germline and Their Potential Implications in Meiotic Differentiation
by Yasmin Striedner, Barbara Arbeithuber, Sofia Moura, Elisabeth Nowak, Ronja Reinhardt, Leila Muresan, Renato Salazar, Thomas Ebner and Irene Tiemann-Boege
Genes 2024, 15(2), 191; https://doi.org/10.3390/genes15020191 - 30 Jan 2024
Cited by 1 | Viewed by 864
Abstract
Advanced paternal age increases the risk of transmitting de novo germline mutations, particularly missense mutations activating the receptor tyrosine kinase (RTK) signalling pathway, as exemplified by the FGFR3 mutation, which is linked to achondroplasia (ACH). This risk is attributed to the expansion of [...] Read more.
Advanced paternal age increases the risk of transmitting de novo germline mutations, particularly missense mutations activating the receptor tyrosine kinase (RTK) signalling pathway, as exemplified by the FGFR3 mutation, which is linked to achondroplasia (ACH). This risk is attributed to the expansion of spermatogonial stem cells carrying the mutation, forming sub-clonal clusters in the ageing testis, thereby increasing the frequency of mutant sperm and the number of affected offspring from older fathers. While prior studies proposed a correlation between sub-clonal cluster expansion in the testis and elevated mutant sperm production in older donors, limited data exist on the universality of this phenomenon. Our study addresses this gap by examining the testis-expansion patterns, as well as the increases in mutations in sperm for two FGFR3 variants—c.1138G>A (p.G380R) and c.1948A>G (p.K650E)—which are associated with ACH or thanatophoric dysplasia (TDII), respectively. Unlike the ACH mutation, which showed sub-clonal expansion events in an aged testis and a significant increase in mutant sperm with the donor’s age, as also reported in other studies, the TDII mutation showed focal mutation pockets in the testis but exhibited reduced transmission into sperm and no significant age-related increase. The mechanism behind this divergence remains unclear, suggesting potential pleiotropic effects of aberrant RTK signalling in the male germline, possibly hindering differentiation requiring meiosis. This study provides further insights into the transmission risks of micro-mosaics associated with advanced paternal age in the male germline. Full article
(This article belongs to the Special Issue Genomic Mosaicism in Human Development and Diseases)
►▼ Show Figures

Figure 1

12 pages, 643 KiB  
Article
Choosing the Best Tissue and Technique to Detect Mosaicism in Fibrous Dysplasia/McCune–Albright Syndrome (FD/MAS)
by Yerai Vado, Africa Manero-Azua, Arrate Pereda and Guiomar Perez de Nanclares
Genes 2024, 15(1), 120; https://doi.org/10.3390/genes15010120 - 18 Jan 2024
Cited by 1 | Viewed by 923
Abstract
GNAS-activating somatic mutations give rise to Fibrous Dysplasia/McCune–Albright syndrome (FD/MAS). The low specificity of extra-skeletal signs of MAS and the mosaic status of the mutations generate some difficulties for a proper diagnosis. We studied the clinical and molecular statuses of 40 patients [...] Read more.
GNAS-activating somatic mutations give rise to Fibrous Dysplasia/McCune–Albright syndrome (FD/MAS). The low specificity of extra-skeletal signs of MAS and the mosaic status of the mutations generate some difficulties for a proper diagnosis. We studied the clinical and molecular statuses of 40 patients referred with a clinical suspicion of FD/MAS to provide some clues. GNAS was sequenced using both Sanger and Next-Generation Sequencing (NGS). We were able to identify the pathogenic variants in 25% of the patients. Most of them were identified in the affected tissue, but not in blood. Additionally, NGS demonstrated the ability to detect more patients with mosaicism (8/34) than Sanger sequencing (4/39). Even if in some cases, the clinical information was not complete, we confirmed that, as in previous works, when the patients were young children with a single manifestation, such as hyperpigmented skin macules or precocious puberty, the molecular diagnosis was usually negative. In conclusion, as FD/MAS is caused by mosaic variants, it is essential to use sensitive techniques that allow for the detection of low percentages and to choose the right tissue to study. When not possible, and due to the low positive genetic rate, patients with FD/MAS should only be genetically tested when the clinical diagnosis is really uncertain. Full article
(This article belongs to the Special Issue Genomic Mosaicism in Human Development and Diseases)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-2
Back to TopTop