Purpose: To systematically study somatic variants arising during development in the human brain across a spectrum of neurodegenerative disorders.
Methods: In this study we developed a pipeline to identify somatic variants from exome sequencing data in 1461 diseased and control human brains. Eighty-eight percent of the DNA samples were extracted from the cerebellum. Identified somatic variants were validated by targeted amplicon sequencing and/or PyroMark® Q24.
Results: We observed somatic coding variants present in >10% of sampled cells in at least 1% of brains. The mutational signature of the detected variants showed a predominance of C>T variants most consistent with arising from DNA mismatch repair, occurred frequently in genes that are highly expressed within the central nervous system, and with a minimum somatic mutation rate of 4.25 × 10 per base pair per individual.
Conclusion: These findings provide proof-of-principle that deleterious somatic variants can affect sizeable brain regions in at least 1% of the population, and thus have the potential to contribute to the pathogenesis of common neurodegenerative diseases.
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http://dx.doi.org/10.1038/s41436-018-0274-3 | DOI Listing |
BMC Biol
January 2025
Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China.
Background: Plant mitochondrial genomes (mitogenomes) exhibit extensive structural variation yet extremely low nucleotide mutation rates, phenomena that remain only partially understood. The genus Gossypium, a globally important source of cotton, offers a wealth of long-read sequencing resources to explore mitogenome and plastome variation and dynamics accompanying the evolutionary divergence of its approximately 50 diploid and allopolyploid species.
Results: Here, we assembled 19 mitogenomes from Gossypium species, representing all genome groups (diploids A through G, K, and the allopolyploids AD) based on a uniformly applied strategy.
J Pediatr Hematol Oncol
January 2025
Cook Children's Medical Center, Fort Worth, TX.
Kaposiform lymphangiomatosis (KLA) is a rare and aggressive subtype of complex lymphatic anomalies (CLA), characterized by abnormal lymphatic proliferation leading to distinct clinical manifestations. Despite the complexity of this condition, there is no established standard therapy, and treatment options such as sclerotherapy, laser therapy, and surgery remain variably effective and are limited to symptom management rather than curative. Sirolimus, an mTOR pathway inhibitor, has shown promise as a primary therapy, particularly in patients without a driver mutation.
View Article and Find Full Text PDFAm J Med Genet A
January 2025
Genetic Health Queensland, Royal Brisbane and Women's Hospital, Herston, Australia.
We describe the phenotypic and genotypic spectrum of patients with vascular anomaly (VA) in a paediatric multi-disciplinary VA clinic. We measured the clinical utility of genotyping by comparing pre and posttest diagnosis and management. A 46-month retrospective analysis occurred for 250 patients offered genetic testing in the VA clinic.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Department of Clinical Pathology, San Giovanni Addolorata Hospital, Rome, Italy.
Background: Ovarian Cancer is one of the leading causes of cancer death among women worldwide and the therapeutic landscape to treat it is constantly evolving. One of the major points of decision for the treatment choice is the presence of some genomic alterations that could confer sensitivity to the new available therapies including inhibitors of poly (ADP-ribose) polymerase (PARPi) with BRCA1 and 2 genes playing the most important role.
Methods And Results: We performed the search for any somatic and/or germline alteration in patient's samples by next generation sequencing (NGS).
Gigascience
January 2025
Department of Genetics and Genomic Sciences, Department of Artificial Intelligence and Human Health, Center for Transformative Disease Modeling, Tisch Cancer Institute, Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Background: Cancer mutations are often assumed to alter proteins, thus promoting tumorigenesis. However, how mutations affect protein expression-in addition to gene expression-has rarely been systematically investigated. This is significant as mRNA and protein levels frequently show only moderate correlation, driven by factors such as translation efficiency and protein degradation.
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