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X chromosome revival in older women increases autoimmune disease risk

  • May 22, 2024
  • Posted by: OptimizeIAS Team
  • Category: DPN Topics
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X chromosome revival in older women increases autoimmune disease risk

Sub: Science and tech

Sec: Health

Tags: X chromosome

Context:

  • Scientists have found a molecular link between altered X-chromosome inactivation and autoimmune diseases.

What is the X chromosome?

  • The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. 
  • It is a part of the XY sex-determination system and XO sex-determination system.
  • In mammals, the females have two copies of the X chromosome while the males carry a single copy. The X chromosome is more significant than its role in determining sex.
  • Each person usually has one pair of sex chromosomes in each cell.
  • Females typically have two X chromosomes, while males typically have one X and one Y chromosome.
  • The X chromosome spans about 155 million DNA building blocks (base pairs) and represents approximately 5 percent of the total DNA in cells.

Diseases linked to X chromosome:

  • A loss of function of these genes could thus lead to a variety of genetic diseases.
  • The diseases whose onset and/or progression the X chromosome influences can be grouped into three types:
    • (i) X-linked genetic diseases, 
    • (ii) diseases influenced by XCI escape, and 
    • (iii) those linked to X-chromosome aneuploidy.
  • Red-green color blindness is X-linked, and affects around 8% of males.
  • Duchenne muscular dystrophy, caused by mutations in the dystrophin gene and affecting 1 in every 3,500-5,000 boys born in India.
  • Agammaglobulinemia, an immunodeficiency disorder that affects around 1 in 200,000 live births, are also X-linked.
  • Klinefelter syndrome is characterized by an extra X chromosome (XXY) and Turner’s syndrome by a loss of one X chromosome in females (X instead of XX).

Inactivation of the X chromosome:

  • In mammalian species, the females typically carry two X chromosomes while males possess one X and one Y chromosome.
  • Each of the X chromosomes is inherited from the parents. 
  • Since females have two copies of the X chromosome, one of the X chromosomes is randomly inactivated during early embryonic development, in a process called X chromosome inactivation (XCI), to prevent the overexpression of X-linked genes in females.
  • In this process, epigenetic changes silence most genes on one X chromosome (epigenetics refers to the processes by which genes are influenced by the environment in which they operate).
  • Issues such as incomplete inactivation or skewed inactivation can lead to the abnormal expression of genes, which contributes to diseases including X-linked disorders, certain cancers, and autoimmune conditions.
  • Researchers unraveled the molecular mechanisms of X inactivation when they discovered Xist, a non-protein-coding RNA. 
  • The body deactivates the X chromosome with the help of Xist and another non-protein-coding RNA, called Tsix (reverse of Xist).
  • The differential regulation of these two genes means, in the X chromosome that is to be deactivated, the Xist RNA is overexpressed such that it coats or covers the chromosome.

Linkage between X chromosome and Autoimmune diseases:

  • Number of immune diseases — including systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome are more common in females than males. 
  • The reactivation of specific X-linked genes in response to XCI alteration varies across immune cell types, which is to say diverse molecular pathways are affected.
  • The resulting effects in autoimmune diseases are likely due to a combination of reactivation events in different cell types and global changes in gene expression.

Linkage between X chromosome  and Alzheimer’s disease:

  • Another disease with a sex bias and linked to the X chromosome is Alzheimer’s disease. 
  • Women seem to have a higher risk of getting it, almost twice as many women have Alzheimer’s as men.
  • A Gene called ubiquitin specific peptidase 11 (USP11), involved in a protein modifying process, encourages tau protein to accumulate in the brain.
  • The researchers suggested the gene escapes X inactivation and is expressed more in females. This also opens new avenues to develop treatments for Alzheimer’s.

Terms in news:

Epigenetics:

  • Epigenetics is the study of how cells control gene activity without changing the DNA sequence.

Y chromosome:

  • The Y chromosome is one of two sex chromosomes in therian mammals and other organisms.
  • Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining because it is the presence or absence of Y chromosome that determines the male or female sex of offspring produced in sexual reproduction.

Autoimmune diseases:

  • An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms.
Science and tech X chromosome X chromosome revival in older women increases autoimmune disease risk

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