3 epigenetics

One active X chromosome and one inactive X chromosome are present in female cells for dosage compensation.

The inactive X chromosome in female cells condenses into a dense structure called the Barr Body.

Xist is an essential non-coding RNA transcribed from the X-inactivation center (XIC) of the inactive X chromosome. It coats the inactive X chromosome and triggers silencing.

Tsix is a non-coding RNA transcribed antisense to Xist and serves as a regulator for Xist expression.

Xist-dependent silencing occurs in a step-by-step process involving primary and secondary silencing factors, and ultimately leads to long-term maintenance of the inactive X chromosome.

The inactive X chromosome is characterized by specific chromatin modifications, such as histone deacetylation, DNA methylation, and enrichment of specific histone variants, all contributing to gene silencing.

The X-inactivation status is inherited through cell division, ensuring that the same X chromosome remains inactive in all daughter cells.

The process by which cloned individuals, despite being genetically identical, can exhibit different coat patterns due to the random nature of X-inactivation in each cell during early development.

Genetic disorders caused by mutations in genes located on the X chromosome. These disorders are often more prevalent in males because they only have one X chromosome, whereas females have two.

A pattern of inheritance where a recessive mutation on the X chromosome is passed from a parent to their child. The expression of the disorder can vary depending on the sex of the child and which parent carries the mutation.

A female individual who carries a recessive mutation on one of her X chromosomes but does not exhibit the disorder. She can still pass the mutation on to her children.

An individual with two copies of the mutated gene, one on each X chromosome, resulting in the expression of the X-linked recessive disorder.

A bleeding disorder caused by a deficiency in clotting factor VIII, a protein crucial for blood clotting. It is an X-linked recessive disorder.

An individual who inherits a mutation on the X chromosome from their mother.

An individual who inherits a mutation on the X chromosome from their father.

X-linked disorders can affect females with the same mutation in different ways depending on which X chromosome is predominantly inactivated. If the mutant X is inactivated, they have a normal phenotype, but if the normal X is inactivated, they exhibit the disease phenotype.

Monozygotic, identical twins with the same X-linked mutation can show varying phenotypes due to skewed X-inactivation. One twin might inactivate their mutant X (normal phenotype), while the other inactivates their normal X (disease phenotype).

Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene, which encodes a protein crucial for regulating gene expression by binding to methylated DNA regions.

Researchers have developed a knock-out mouse model for Rett syndrome that mimics many human symptoms, and a study showed that restoring MECP2 expression in these mice reversed neurological issues and extended lifespan.

Current understanding of X-inactivation suggests it's a stable process in most cells once established. Reactivating an inactive X chromosome could be challenging, but potential therapeutic strategies are being explored for Rett syndrome and other X-linked disorders.

Females with a dominant X-linked condition can have a normal phenotype if the dominant allele is on the active X chromosome.

Females with a recessive X-linked condition can be carriers, meaning they have one normal and one mutated allele.

In conditions where the phenotype depends on a circulating product, the effect of the mutated allele is averaged out in females due to having both normal and mutant cells.

Female carriers of X-linked recessive conditions can have an intermediate phenotype due to the averaging effect of normal and abnormal cells.

Females with a recessive X-linked condition can show patches of normal and abnormal tissues if the phenotype is a localized property of individual cells.

In conditions where the phenotype is a localized property of individual cells, female carriers can have a mosaic phenotype, showing patches of normal and abnormal tissues. This is because the inactivation of the X chromosome is random, leading to different tissues with different X chromosome expressions.

Hypohidrotic ectodermal dysplasia and Duchenne muscular dystrophy are examples of X-linked recessive conditions where female carriers show patches of normal and abnormal tissue.

Haemophilia A is an example of an X-linked recessive condition where female carriers have an intermediate phenotype, clinically unaffected, but biochemically abnormal.

A genetic disorder that affects the development of hair, teeth, and sweat glands, primarily affecting males due to its X-linked recessive inheritance.

A gene located on the X chromosome that is responsible for the development of ectodermal structures such as hair, teeth, and sweat glands. Mutations in this gene cause X-linked Hypohidrotic Ectodermal Dysplasia.

A condition where individuals inherit a single copy of a dominant gene mutation on the X chromosome.

Females with a recessive X-linked condition may experience some symptoms due to random X-inactivation where some cells express the mutated gene.

A test used to determine the functionality of sweat glands. Areas with functional sweat glands turn brown due to iodine reaction, while areas without functional sweat glands remain yellow.

The state of having two different alleles, one from each parent, for a particular gene.

The state of having two identical copies of an allele for a specific gene.

A genetic condition where a person inherits a dominant gene mutation but does not show any symptoms.