Genetics Chromosomes and Chromosomal Disorders Flashcards
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Acquired chromosomal abnormalities:
Etiology: […]
Clinical spectrum: […]
Constitutional chromosomal abnormality (born with it):
Etiology: - […]
Examples: […]
Acquired chromosomal abnormalities:
Etiology:* problem with chromosome replication/mitosis*
Clinical spectrum: many present as cancers. Chronic myeloid leukemia, solid tumors
Constitutional chromosomal abnormality (born with it):
Etiology: - Chromosomal abnormality was present in sperm/egg that formed this person
- abnormality in sperm/egg may have arose spontaneously or passed down from parents
Examples: . trisomy 21 or monosomy X
Chromosomal variant is said to be present if […]
Chromosomal variant is said to be present if there is a variation in the amount of a whole/part of a chromosome and/or a change in the position of a chromosome(s)
The origin of chromosomal abnormalities can be constitutional (born with) or aquired (not born with)
Chronic Myeloid Leukemia (CML) is an acquired chromosomal abnormality that is characterized by the […]
When is CML suspected?
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How is CML confimed?
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What is the Philadelphia Chromosome?
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How does the BCR-ABL fusion gene cause CML?
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How is CML treated?
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No need to memorize anything. Just read and understand cuz genetics is MCQ.
Chronic Myeloid Leukemia (CML) is an acquired chromosomal abnormality that is characterized by the **replacement of the bone marrow with a particular type of malignant, leukemic cells. **
When is CML suspected?
It is often suspected when full blood count shows increased granulocytes of ALL types
How is CML confimed?
- **Bone marrow aspiration and biopsy findings done as part of evaluation, but can be insufficent to confirm diagnosis. **
- Presense of philadelphia chromosome helps to confirm diagnosis of CML
What is the Philadelphia Chromosome?
Philadelphia chromosome is an abnormally short chromosome formed by translocation between ABL gene of chromosome 9 and BCR gene of chromosome 22
2 fusion genes are formed:
1. BCR-ABL on Ph chromosome
2. ***ABL-BCR on the chromosome 9 participating in translocation
*
How does the BCR-ABL fusion gene cause CML?
***The BCR-ABL fusion gene makes protein that has uncontrolled tyrosine kinase activity, leads to constitutive cell growth, giving rise to cancer
*
How is CML treated?
Use imatinib mesylate to get patient into remission, then do bone marrow transplant.
- Chemotherapy works but not that well
The commonest of autosomal trisomy disease is
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What are the 3 causes?
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The commonest of autosomal trisomy disease is
Down syndrome
What are the 3 causes?
1. **Non dysjunction (92%) **- meisosis error, didn’t divide the chromosomes. can be either parents. Little risk in next pregnancy.
- **translocation (3-4%) **- chromosome 21 stuck on another chromosome number (This can be de-novo OR inherited from either parents)
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**mosaic (2-4%) **
- post-zygotic mutation
- Hence some cells with have trisomy 21, some cells would be normal
- milder symptoms (can test heart, lungs, etc. but cannot test function of brain)
- risk of recurrence is usually low
It is important to determine the cause because risk of having another child depends on the cause
Prognosis is different (mosaic down syndrome children have milder clinical features)
What are the 2 types of chromosomal abnormalities?
- […]
- […]
What are the 2 types of chromosomal abnormalities?
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numerical abnormality - abnormal number of chromosomes
- from problem with separation (nondisjunction) or mitosis/meiosis
- aneuploidy –> gain or loss in one or two chromosomes
- polyploidy –> gain of a complete haploid set of chromosomes
- gain is better than loss
- sex chromosomal abnormalities have less severe consequence than autosomal -
structural abnormality
- deletion, duplication, insertion, translocation, inversion, ring, marker
- from problem with mitosis/meiosis
- loss or gain of genes, affecting gene expression
- break in chromosome may alter product of a gene
What are the functions of these components in a chromosome?
Telomere
- Maintains […]
- Ensures […]
- Helps establish […]
Centromere
- Essential for […]
What are the functions of these components in a chromosome?
Telomere
- Maintains integrity of chromosome
- Ensures complete replication of ends of chromosomes
- Helps establish chromosome pairing
Centromere
- Essential for segregation during cell division
Both are made up of specific DNA sequences
What is the test used to visualize chromosomes?
[…]
What is the test used to visualize chromosomes?
Giemsa banding karyotype (standard chromosomal analysis)
Other ways to analyze chromosome include FISH and chromosomal microarray analysis
What is X-inactivation?
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What is X-inactivation?
X-inactivation (lyonization) is when one of the two X chromosome in a female is inactivated
- Inactivation is random and occurs early in embronic development
- Once it occurs, it is “transmitted” to all cells that hail from it (except egg cells)
- Allows for dose compensation (both sex have same number of active genes)
**Has implications on the manifestations of sex-linked diseases in females **
**Note that x-inactivation is PHYSIOLOGICAL, and its responsible for mosaicism in females. **
“Because of this X inactivation, all women are natural mosaics: although all their cells have the same two chromosomes, one from each parent, the mother’s copy works in some cells, while the father’s works in the others.”
