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DNA inversions in bacteria were known to create diversity through intergenic or partial intergenic changes. Now, Chanin, West, et al. reveal intragenic inversions, enabling single genes to encode multiple protein variants via sequence recoding or truncation - an unexpected mechanism for expanding protein diversity without increasing genome size.
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http://dx.doi.org/10.1016/j.tig.2024.12.002 | DOI Listing |
J Med Genet
August 2025
LBMMS, Service de Biochimie et Biologie moléculaire, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, Auvergne-Rhône-Alpes, France.
11β-hydroxylase deficiency (11βOHD) is the second most common cause (5%) of congenital adrenal hyperplasia (CAH). The gene shares 95% of genomic sequence homology with and therefore Sanger sequencing remains the gold standard. We present a case of 11βOHD due to an intragenic inversion in that was missed by both the Sanger sequencing and massive parallel sequencing (MPS) methods.
View Article and Find Full Text PDFPathol Res Pract
August 2025
Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, China. Electronic address:
Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The 5th edition of the World Health Organization (WHO) Classification of Thyroid Tumors divides PTC into 13 distinct morphological subtypes based on its morphological characteristics. According to molecular features, thyroid cancer is classified into RAS-like and BRAF-like tumors.
View Article and Find Full Text PDFAm J Hum Genet
June 2025
Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium. Electronic address:
8q21.11 microdeletions involving ZFHX4 have previously been associated with a syndromic form of intellectual disability, hypotonia, unstable gait, and hearing loss. We report on 63 individuals-57 probands and 6 affected family members-with protein-truncating variants (n = 41), (micro)deletions (n = 21), or an inversion (n = 1) affecting ZFHX4.
View Article and Find Full Text PDFClin Chem
January 2025
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Background: Genetic testing has traditionally been divided into molecular genetics and cytogenetics, originally driven by the use of different assays and their associated limitations. Cytogenetic technologies such as karyotyping, fluorescent in situ hybridization or chromosomal microarrays are used to detect large "megabase level" copy number variants and other structural variants such as inversions or translocations. In contrast, molecular methodologies are heavily biased toward subgenic "small variants" such as single nucleotide variants, insertions/deletions, and targeted detection of intragenic, exon level deletions or duplications.
View Article and Find Full Text PDFTrends Genet
March 2025
National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. Electronic address: