Molecular Mechanisms and Genetics of Human Disease

Dear Colleagues,

Genetic disorders vary greatly in their occurrence in different ethnic and geographic populations. For example, sickle cell anemia is more common among people of African descent, phenylketonuria is notably prevalent in Celtic and Northern European groups, Tay-Sachs disease has a higher incidence in Ashkenazi Jewish communities, and cystic fibrosis occurs more frequently in European and American Caucasian populations. Although many of these conditions have traditionally been explained as being the result of single-gene defects caused by point mutations, emerging evidence points to the critical role of larger chromosomal rearrangements (e.g., insertions, deletions, and duplications) in shaping disease etiology. Autosomal dominant neuropathies illustrate this principle particularly well. Charcot–Marie–Tooth disease type 1A (CMT1A) stems from a reciprocal duplication on chromosome seventeen, while hereditary neuropathy with a liability to pressure palsy (HNPP) arises from a corresponding deletion at the same locus. These structural variants are often the result of aberrant recombination events that can introduce either surplus or deficit copies of essential genes. Collectively, these observations indicate that genomic instability and rearrangements, rather than point mutations alone, can underpin the onset and progression of complex genetic disorders. Recently, the notion of structural rearrangements being a unifying mechanism for distinct clinical phenotypes has gained traction. Introducing copy number variations or altering gene organization can lead to both loss-of- and gain-of-function mutations, causing an extensive range of molecular and clinical outcomes. With this in mind, we invite contributions to this Special Issue that explore the molecular underpinnings of genetic disorders, especially those driven by genomic rearrangements. Of particular interest will be studies that elucidate how these structural alterations affect gene expression, protein function, and disease phenotypes, as they hold promise for advancing our understanding of pathogenesis and the development of innovative therapeutic strategies.

In this Special Issue, original research articles and reviews are welcome. Their research areas may include (but are not limited to) the following: 

1. Genomic variation in disease onset and progression;
2. Alteration of chromatin architecture causing aberrant transcriptional regulation;
3. Impaired protein interactions;
4. Structural variations (insertion/deletion, duplication, and translocations).

I look forward to receiving your contributions. 

Dr. Rais Ahmad Ansari
Dr. Ata Abbas
Guest Editors

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. Biomolecules 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 2700 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.

• genomic rearrangement
• genetic diseases
• molecular mechanism
• recombination
• gene duplication