Numerical and structural abnormalities Flashcards
What is aneuploidy?
A condition in which a person has one or more chromosomes above or below the normal chromosome number.
What gives rise to aneuploidy?
Non-disjunction
What is non-disjunction?
The failure of chromosome pairs to separate properly during cell division.
Non-disjunction gives rise to what two types of cell lines?
Monosomy and trisomy cell lines.
What usually happens to the monosomy cell line that results from non-disjunction?
It is likely to be severely disadvantaged and most likely will die out.
Non-disjunction at mitosis can result in what outcome (if viable)?
Mosaicism
What is mosaicism?
An individual in which some cells are normal and some are abnormal.
Non-disjunctions are more common in what kind of cell division?
Meiosis
Approximately how many conceptions are monosomic or trisomic?
25%
What is the term for the way in which chromosomes are distributed in meiosis?
Segregation
Scenario: all four gametes produce a child.
What would be the ratio of normal, trisome, and monosomy if non-disjunction occurred during meiosis I?
No normal, two trisomy, two monosomy.
Scenario: all four gametes produce a child.
What would be the ratio of normal, trisome, and monosomy if non-disjunction occurred during meiosis II?
Two normal, one trisomy, one monosomy.
What is the ISCN denotation for a translocation?
t
What is a translocation?
A two-way exchange of material between two chromosomes.
What is the most common type of translocation?
Balanced reciprocal translocation
What is meant by ‘balanced’ in a balanced reciprocal translocation?
Balanced means that no total genetic material was lost or gained in the translocation.
What is meant by ‘reciprocal’ in a balanced reciprocal translocation?
Reciprocal means that the genetic material from the two chromosomes was exchanged with each other.
Does a balanced reciprocal translocation always occur between the same arms of the chromosomes?
No (not necessarily)
How common are translocations in the normal population?
1 in 600
How does a reciprocal translation occur?
Breaks occur in one arm of each chromosome and the portions of chromosome material distal to the breakpoints switch positions.
Breaks occurring in one arm of each chromosome and the portions of chromosome material distal to the breakpoints switching positions is a description of what type of structural abnormality?
Translocation
What is the term for the portions exchanged between chromosomes in reciprocal translocation?
Translocated segments
What is the term for the remainder of the chromosome (the portions NOT exchanged) including the centromere in reciprocal translocation?
Centric segment
What is a centric segment?
The remainder of chromosomes including the centromere (i.e. the portions NOT exchanged) in reciprocal translocation.
What is the term used for the rearranged chromosome following translocation?
Derivative chromosome (der).
What is the ISCN denotation for a derivative chromosome?
der
What is a derivative chromosome?
A rearranged chromosome following translocation.
How are derivative chromosomes identified?
By which centromere it possesses.
What type of chromosome is identified by which centromere it possesses?
Derivative chromosome
What would be the denotation for a chr 5 with part of a translocated p arm from chr 10?
der(5)
What would be the denotation for a chr 10 with part of a translocated q arm from chr 5?
der(10)
Do balanced translocation carriers display phenotypical abnormalities?
No
Do unbalanced translocation carriers display phenotypical abnormalities?
Yes
What type of issues do balanced translocation carriers often have?
Fertility issues, often involving multiple consecutive miscarriages.
Is it possible for a balanced translocation carrier to produce a genetically and phenotypically normal offspring?
Yes
Scenario: all four gametes produce a child.
What would be the ratio of normal : balanced translocation carrier : unbalanced translocation carrier in the offpring of a balanced translocation carrier and a normal genotype?
1 normal : 1 balanced translocation carrier : 2 unbalanced translocation carriers.
Note: these are abnormalities and in reality do not follow the rules of a Punnett square.
Are unbalanced translocation carriers usually the offspring of balanced translocation carriers or unbalanced translocation carriers?
Balanced translocation carriers.
What is an unbalanced translocation?
A translocation in which genetic material is lost and gained.
What determines the phenotype of an unbalanced translocation carrier?
The amount of material that is lost and gained.
Consider which genes are lost or gained, where they are used in the body, and how commonly they are used.
What is a Robertsonian translocation?
Fusion of two acrocentric chr with loss of p arm material.
What is the term for fusion of two acrocentric chr with loss of p arm material?
Robertsonian translocation.
Is a Robertsonian translocation balanced or unbalanced?
Robertsonian translocations are considered balanced.
How many chr do Robertsonian translocation carriers have?
45
Why are Robertsonian translocations considered balanced?
They are fusions of acrocentric chr with loss of p arm material - satellites don’t contain important genetic material, so they are considered balanced.
Which structural abnormality reduces the number of chr to 45 but is still considered balanced?
Robertsonian translocation
What is the most common balanced chr rearrangement?
Robertsonian translocation
How common are Robertsonian translocations?
1 in 1000
Which acrocentric chromosomes can be involved in Robertsonian translocations?
All acrocentric chr - 13, 14, 15, 21, and 22.
Which chromosomes can be involved in Robertsonian translocations?
All acrocentric chromosomes - 13, 14, 15, 21, and 22.
Are Robertsonian translocations a numerical or a structural abnormality?
Both!
What are the most important/clinically relevant Robertsonian translocations?
Those involving chr 21 as they are the basis of most cases of familial Down syndrome.
What are the two possible ISCN denotations for a Robertsonian translocation?
der or rob
What is the denotation for the breakpoints in a Robertsonian translocation?
q10
This is used as a fictional breakpoint representing the centre of the centromere.
Why does a Robertsonian translocation reduce the chr number to 45?
Two acrocentric chr are fused and the two displaced satellites recombine and are lost.
What is the karyotype of a female with a Robertsonian translocation between chr 13 and chr 14?
45,XX,rob(13;14)(q10;q10)
OR
45,XX,der(13;14)(q10;q10)
What is the karyotype of a male with a Robertsonian translocation between chr 13 and chr 15?
45,XY,rob(13;15)(q10;q10)
OR
45,XY,der(13;15)(q10;q10)
