In Vitro Cellular Aging and Immortalization
George E. Milo, Bruce C. Casto, Charles F. Shuler in Transformation of Human Epithelial Cells: Molecular and Oncogenetic Mechanisms, 2017
Ning et al.22 further showed that introduction of a normal human chromosome 4 into cell lines assigned to complementation group B restored the phenotype of limited proliferative potential. However, when the human chromosome 4 was introduced into cell lines assigning to the other complementation groups (A, C, and D), there was no decrease in proliferation potential and the phenotype of immortality was retained. Thus, it seems clear that genes on chromosome 4 code for some part of the genetic program that limits the division potential of normal cells in culture. Disruption of these genes leads to cells with an immortal phenotype. Sugawara et al.23 found a similar result in studies in which they introduced the normal human chromosome 1 into Chinese hamster cells. Human chromosome 1 was able to restore the cellular aging phenotype in these immortal hamster cells. It remains to be seen whether chromosome 1 plays a role in the immortalization of human cells.
The Role of Biology in the Courtroom
Gail S. Anderson in Biological Influences on Criminal Behavior, 2019
In two other Dutch cases, the court considered that pedophilia was genetic. In one, the defense counsel argued that his client’s sexual orientation, which resulted in his addiction to child pornography, was not under his control, so he should not be considered criminally responsible. The court did not accept these arguments, stating that the defendant may not be able to control his pedophilic orientation but he could control his pedophilic activities, such as collecting and distributing child pornography and assaulting a child.6 In a more unusual genetic case in the Netherlands, Huntington’s disease, the result of a single gene variant on chromosome 4, was used as both an aggravating and a mitigating factor. The accused was convicted of arson after he attempted to burn down his girlfriend’s house, endangering her life and several others’. Huntington’s disease is a progressive disease that causes dementia and an inability to deal with problems and can possibly result in impulsive aggression. He was found not criminally responsible for the crime (mitigating) but was confined to a psychiatric institution indefinitely to prevent recidivism, due to the expected progression of the disease (aggravating).6
Self-harm
Anne Stephenson, Martin Mueller, John Grabinar, Janice Rymer in 100 Cases in General Practice, 2017
Huntington's disease is a single gene disorder caused by a malfunctioning gene on chromosome 4. It is an autosomal dominant disease and is a progressive neurodegenerative disorder. If one parent has the disorder their children will have a 50% chance of having the faulty gene and all people who have this gene will develop the disease at some stage. The condition affects about 1 in 15,000 people across much of the world and equally affects men and women. The early symptoms vary but can include memory loss or confusion, changes in personality and mood and slight uncontrolled muscle movements. As the disease progresses, these symptoms become more severe and it is invariably fatal. The early symptoms usually start between 30 and 50 years of age but it can start at any age and symptoms can differ from person to person. A genetic test is available.
State-of-the-art pharmacological approaches to reduce chorea in Huntington’s disease
Published in Expert Opinion on Pharmacotherapy, 2021
Jessie S. Gibson, Daniel O. Claassen
Huntington’s disease (HD) is an autosomal dominant, neurodegenerative disease caused by an expansion of CAG trinucleotide repeats on chromosome 4. HD is characterized by abnormal involuntary movements, cognitive decline, and behavior changes. Chorea is the most prominent symptom of HD, and average onset is in the 4th or 5th decade of life. In 1872, George Huntington published an early description of chorea as an irregular, spasmodic dance-like movement that, in HD, progresses to every voluntary muscle in the body [1]. In the following years, the disease was called ‘Huntington’s chorea’, and not for another century did ‘Huntington’s disease’ become more-widely used, acknowledging that HD is typified by more than chorea alone. Even so, chorea remains a focal component of modern HD treatment and investigation. In fact, participation in most HD clinical trials hinges on a diagnosis of ‘motor-manifest’ HD. In the years since HD was first described, a number of advances have been made. Most notable was the isolation of the HD gene in 1993. Since that time, breakthroughs have come in the form of pharmacological treatments to reduce chorea. Here we aim to describe HD chorea and approaches for management, as well as promising directions in HD research.
Deutetrabenazine for the treatment of Huntington’s chorea
Published in Expert Review of Neurotherapeutics, 2018
Hassaan Bashir, Joseph Jankovic
Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene on chromosome 4, which encodes an expanded polyglutamine stretch in the huntingtin protein [1]. Its progressive and ultimately fatal course is characterized by motor disturbances, cognitive decline and psychiatric manifestations. Chorea, a hyperkinetic movement disorder, is the most common presenting and troublesome motor manifestation of HD. It may interfere with daily activities, reduce quality of life and cause self-injury, but in advanced cases chorea subsides as a hypokinetic-rigid state emerges [2]. In contrast to chorea, which is the typical motor symptom of adult HD, parkinsonism characterizes the motor manifestation of juvenile-onset HD [3].
Identifying Similarities and Disparities Between DNA Copy Number Changes in Cancer and Matched Blood Samples
Published in Cancer Investigation, 2019
Nezamoddin N. Kachouie, Wejdan Deebani, David C. Christiani
Table 2 summarizes the number of locations with corresponding MIC values greater than specified threshold of 0.5, 0.55, or 0.6 for each chromosome. MIC values above 0.5 indicate substantial correlations (similarities) between the cancer and the blood sample which is potentially related to the early stage of cancer. We should point out that the numbers of locations with MIC values exceeding the thresholds are cumulative. That is the numbers of locations with MIC values higher than 0.55 contains numbers of locations with MIC values higher than 0.6, and similarly the numbers of locations with MIC values higher than 0.5 contains numbers of locations with MIC values higher than 0.55 and higher than 0.6. As shown in Table 2, chromosome 2 has the highest number of locations with MIC values exceeding all three thresholds. There are 594 locations with MICs above 0.5, among them 199 locations with MICs above 0.55 from which 58 locations with MICs above 0.6 in this chromosome. Chromosome 4 is in the second place with regard to the number of locations with MIC values exceeding 0.5. However, it is in the third place with regard to the locations with MIC values exceeding 0.55 and 0.6. Chromosome 3 is in the third place with 348 locations with MIC values exceeding 0.5. However, it has the second highest number of locations with MIC values exceeding 0.55. Chromosome 12 has the second highest number of locations with MIC values exceeding 0.6. In contrast with chromosomes 2, 3, 4, and 12, chromosome 19 has only 4 locations with corresponding MIC values greater than 0.5, none of them greater than 0.55.
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