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.