Sickle-cell disease in the context of "Oxidative stress"

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👉 Sickle-cell disease in the context of Oxidative stress

Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O
2
(superoxide radical), OH (hydroxyl radical) and H2O2 (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling.

In humans, oxidative stress is thought to be involved in the development of cancer, Parkinson's disease, Lafora disease, Alzheimer's disease, atherosclerosis, heart failure, myocardial infarction, fragile X syndrome, sickle-cell disease, lichen planus, vitiligo, infection, chronic fatigue syndrome, and depression; however, reactive oxygen species can be beneficial, as they are used by the immune system as a way to attack and kill pathogens. Oxidative stress due to noise was estimated at cell level using model of growing lymphocytes. Exposure of sound with frequency 1 KHz and intensity 110 dBA for 4 hours and eight hours per day may induce oxidative stress in growing lymphocytes causing the difference in viable cell count. However the catalase activity depends on duration of exposure. In case of noise exposure of 8 hours per day, it declines significantly as compared to noise exposure of 4 hours per day.

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Sickle-cell disease in the context of J. B. S. Haldane

John Burdon Sanderson Haldane FRS (/ˈhɔːldn/; 5 November 1892 – 1 December 1964), nicknamed "Jack" or "JBS", was a British-born scientist who later moved to India and acquired Indian citizenship. He worked in the fields of physiology, genetics, evolutionary biology, and mathematics. With innovative use of statistics in biology, he was one of the founders of neo-Darwinism. Despite his lack of an academic degree in the field, he taught biology at the University of Cambridge, the Royal Institution, and University College London. Renouncing his British citizenship, he became an Indian citizen in 1961 and worked at the Indian Statistical Institute until his death in 1964.

Haldane's article on abiogenesis in 1929 introduced the "primordial soup theory", which became the foundation for the concept of the chemical origin of life. He established human gene maps for haemophilia and colour blindness on the X chromosome, and codified Haldane's rule on sterility in the heterogametic sex of hybrids in species. He correctly proposed that sickle-cell disease confers some immunity to malaria. He was the first to suggest the central idea of in vitro fertilisation, as well as concepts such as hydrogen economy, cis and trans-acting regulation, coupling reaction, molecular repulsion, the darwin (as a unit of evolution), and organismal cloning.

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Sickle-cell disease in the context of Heterozygote advantage

A heterozygote advantage describes the case in which the heterozygous genotype has a higher relative fitness than either the homozygous dominant or homozygous recessive genotype. Loci exhibiting heterozygote advantage are a small minority of loci. The specific case of heterozygote advantage due to a single locus is known as overdominance. Overdominance is a rare condition in genetics where the phenotype of the heterozygote lies outside of the phenotypical range of both homozygote parents, and heterozygous individuals have a higher fitness than homozygous individuals.

Polymorphism can be maintained by selection favoring the heterozygote, and this mechanism is used to explain the occurrence of some kinds of genetic variability. A common example is the case where the heterozygote conveys both advantages and disadvantages, while both homozygotes convey a disadvantage. A well-established case of heterozygote advantage is that of the gene involved in sickle cell anaemia.

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