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Aneuploidy & Dosage compensation - Coggle Diagram
Aneuploidy & Dosage compensation
Aneuploidy
Definition:
the condition whereby the total number of chromosomes in the organism is not a multiple of a set.
This occurs when an organism has an extra chromosome (trisomy: 2n+1) or lacks a chromosome (monosomy: 2n-1). Aneuploidy may involve more than one chromosome.
Autosomal
Down syndrome
Extra copy of chromosome 21, such that each somatic cell has a total of 47 chromosomes.
(The only viable autosomal aneuploidy) (21 is smallest chromosome)
sex
Turner syndrome
Single X chromosome in individuals. They have only 45 chromosomes and are phenotypically female, but are sterile as their sex organs do not mature.
Klinefelter syndrome
two X chromosomes and one Y chromosome. They are phenotypically male but show some female body characteristics and are sterile.
Cause:
Non-disjunction
An error during meiosis when a pair or pairs of homologous chromosome fail to separate during anaphase I of meiosis or sister chromatids fail to separate during anaphase II of meiosis.
Mechanism:
Mitotic nondisjunction can occur due to the inactivation of either topoisomerase II, condensin, or separase.
Topoisomerase II
enzyme involved in managing the topological problems that arise during DNA replication and chromosome segregation.
Inactivation of topoisomerase II can result in chromosomal entanglements or unresolved DNA linkages that interfere with proper chromosome segregation
Condensin
involved in chromosome condensation, essential for the proper alignment and segregation of chromosomes during mitosis. Inactivation of condensin can lead to improperly condensed chromosomes which are more prone to missegregation during mitosis.
Separase
responsible for cleaving the cohesin protein complexes.
Inactivation of separase can lead to improper cleavage of cohesin complexes, hence chromosome missegregation
Dosage compensation
Problem
XX has twice as many X-linked genes as the XY —> imbalance
The mechanisms to equalise the dosage of X-linked gene products so that both sexes make the same amount.
mammals: X-inactivation
one of the two X chromosomes is randomly inactivated (compacted and transcriptionally silenced): Barr body
Tortoiseshell cats: orange and black coat colour
Dermal Dysplasia: female, patches of normal tissue interspersed with patches of cells that are sweat gland-deficient.
Flies:
transcribing all the genes on the male X at exactly twice the rate of the genes on either of the female X chromosomes.
worm:
slowing down the rate of X-linked expression on the female Xs to half the rate of that in males.
Why should we care...?
Aneuploidy
Understanding aneuploidy helps us comprehend the genetic basis of these disorders
develop strategies for diagnosis, prevention, and treatment.
A common cause of genetic disorders
Dosage compensation
Without dosage compensation, genes on sex chromosomes would be expressed at different levels between males and females, leading to dosage imbalances. Such imbalances can disrupt normal cellular processes.