(searched for: doi:10.1146/annurev-genet-041720-093403)
Cureus, Volume 13; doi:10.7759/cureus.15335
A 57-year-old woman experienced an abnormal feeling on the left side of her neck and difficulty breathing 90 minutes after eating Chinese noodles. She had a history of removal of a left sphenoid ridge meningioma one year earlier. She had experienced rigidity of her left neck and peripheral cold sensation on her left side in winter since approximately 10 years of age. She had experienced peripheral swelling of her left side and lower back pain of unknown origin on her left side several times. She had suffered for oral allergy syndrome since she was young. She sometimes experienced a tingling sensation on her lips and an unpleasant feeling in her throat after eating some types of fruit. On arrival, 180 minutes after eating the noodles, she had clear consciousness and stable vital signs. She had left neck and chest swelling without color change. Her difficulty breathing subsided spontaneously. A blood analysis revealed an increased level of immunoglobulin E. Neck computed tomography (CT) with contrast medium and magnetic resonance imaging (MRI) revealed left-side-limited edema in the subcutaneous area and surrounding esophagus and bronchus. These radiological findings denied hemorrhaging or pseudoaneurysmal formation. She underwent observational admission. After her edema improved, she was discharged on the third hospital day. A follow-up examination one week later showed the complete resolution of the neck and chest edema. A blood allergen test did not reveal the cause of the edema. The mechanism underlying the asymmetric transient edema after eating in the present case may involve somatic mosaic.
Cells, Volume 10; doi:10.3390/cells10051256
Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain-specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotypes. Molecularly, cellular senescence, which seems to be mediated by CIN and aneuploidy, is likely to contribute to brain aging in health and disease. However, there is no consensus about the occurrence of CIN in the aging brain. As a result, the role of CIN/somatic aneuploidy in normal and pathological brain aging is a matter of debate. Still, taking into account the effects of CIN on cellular homeostasis, the possibility of involvement in brain aging is highly likely. More importantly, the CIN contribution to neuronal cell death may be responsible for neurodegeneration and the aging-related deterioration of the brain. The loss of CIN-affected neurons probably underlies the contradiction between reports addressing ontogenetic changes of karyotypes within the aged brain. In future studies, the combination of single-cell visualization and whole-genome techniques with systems biology methods would certainly define the intrinsic role of CIN in the aging of the normal and diseased brain.
Cytogenomics pp 327-348; doi:10.1016/b978-0-12-823579-9.00013-8
Cytogenomic landscape encompasses genomic variations at the chromosomal (subchromosomal) level and chromosome arrangement in interphase. Molecular neurocytogenetics and neurocytogenomics have emerged as valuable tools for uncovering somatic genome (chromosome) variations (aneuploidy, subchromosomal rearrangements, copy number variations) and interphase chromosome organization in interphase nuclei of the normal and diseased brain. Chromosomal mosaicism and instability demonstrate ontogenetic variability in the human brain, which seems to be an integral part of brain development and to mediate either neuronal diversity or neuropsychiatric diseases. Currently, neurocytogenetic (neurocytogenomic) studies continue to bring further important insight into understanding the complexity of the human central nervous system and the mechanisms of brain diseases. The present chapter describes achievements in molecular neurocytogenetics/neurocytogenomics with the special attention paid to systems analysis of pathways shaping the cytogenomic landscape of the human brain.
International Journal of Molecular Sciences, Volume 21; doi:10.3390/ijms21218328
Mechanisms for somatic chromosomal mosaicism (SCM) and chromosomal instability (CIN) are not completely understood. During molecular karyotyping and bioinformatic analyses of children with neurodevelopmental disorders and congenital malformations (n = 612), we observed colocalization of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (n = 47 or 7.7%). Analyzing molecular karyotyping data and pathways affected by CNV burdens, we proposed a mechanism for SCM/CIN, which had been designated as “chromohelkosis” (from the Greek words chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either in partial/whole chromosome loss (e.g., aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g., prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything”, similar to the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome.