Lecture 11: Chromosomal pathology Flashcards
Give the 4 broad chromosomes changes that produce an abnormal change:
1) dosage effect
2) disruption of a gene at a break point
3) position effect
4) unmasking of a recessive disorder
How may a chromosomal change lead to the unmasking of a recessive disorder?
if a dominant chromosome in a heterozygous pair is deleted, a recessive phenotype may present
Give the three types of copy number variation:
1) chromosome number
2) chromosome structure
3) mosaicism
What does aneuploidy mean?
Abnormal number of chromosomes
What does euploidy mean?
normal number of chromosomes
What does polyploidy mean?
condition in which an organism has extra sets of chromosomes
What is chromosome mosaicism?
different cells containing different chromosomal makeup
What is the most common cause of aneuploidy?
meiotic non-disjunction
What is non-dysjunction?
failure of chromosome or chromatid separation
True or false: in aneuploidy, maternal age has a large effect whereas paternal age has little to no effect
true
Describe how non-disjunction in meiosis can cause aneuploidy:
non-disjunction can lead to disomic gamete which will then fuse with a normal monosomic gamete at fertilisation to form a trisomic zygote
What is the name of trisomy 21?
Down syndrome
What is the name of trisomy 13?
Patau syndrome
What is the name of trisomy 18?
Edwards syndrome
Give 5 characteristics of Down syndrome:
1) learning difficulties
2) heart malformations
3) gut atresia
4) early dementia
5) leukaemia
Give 4 characteristics of Patau syndrome;
1) microcephaly
2) holoprosencephaly
3) clefting
4) polydactyl
What is holoprosencephaly?
failure of left and right hemispheres to separate
What is holoprosencephaly?
failure of left and right hemispheres to separate
Give 5 characteristics of Edwards Syndrome:
1) microcephaly
2) growth retardation
3) rocker-bottom feet
4) clenched hands
5) cardiac anomalies
Why is it that only trisomies 21, 18 and 13 are viable?
because chromosomes 21, 18 and 13 are small and have few genes meaning life can still be sustained (larger chromosomes are required for life)
True or false: sex chromosome aneuploidy tends to be more severe than autosomal aneuploidy
False
What is the name of the sex chromosome aneuploidy with just one X chromosome?
of the sex chromosome aneuploidy with just one X chromosome?
Turner syndrome (45 X)
Give 4 characteristics of Tuner syndrome (45 X):
1) short stature
2) infertile
3) neck webbing
4) aortic coarctation
What is the name of the sex chromosome aneuploidy where there are two X chromosomes and one Y chromosome?
Klinefelter syndrome (47 XXY)
True or false: 99% of polyploidy cases result in spontaneous miscarriage
True
How does polyploidy come about?
either an eggy is digyny or there are two sperm (dispermy) at fertilisation
Give two types of cytogenetic chromosome analysis methods:
1) karyotyping
2) FISH
What is FISH (fluorescent in situ hybridization)?
using fluorescent DNA probes to identify specific genes or a lack of
What is the name of the disease caused by a microdeletion at 22q11.2?
DiGeorge Syndrome
Give four DNA based chromosome analysis methods:
1) chromosomal microarrays
2) whole genome sequencing
3) multiple ligation dependent probe amplification
4) quantitative fluorescent PCR
Give three benefits of using chromosomal microarrays over karyotyping:
1) higher resolution
2) greater diagnostic rate
3) only needs DNA, rather than live cells
What type of chromosome change can karyotyping identify that microarrays can’t?
balanced rearrangements
What is copy number variation?
A difference in the amount of a specific DNA sequence found in different individuals
What is copy number variations sequencing?
a method that looks to identify variations in copy numbers by sequencing DNA, cutting it into fragments then using computer alignment to count copy numbers
What is a reciprocal translocation?
where regions of chromosomes break off and exchange with another chromosome
What arrangement is formed by translocated chromosomes when matching up for meiosis?
meiotic quadrivalent/ pachytene cross
Does adjacent segregation of a pachytene cross result in balanced or unbalanced segregation?
Unbalanced
Does alternate segregation of a pachytene cross result in balanced or unbalanced segregation?
Balanced
What is a Robertsonian translocation?
The long arms of two acrocentric chromosomes are joined to a common centromere through translocation, resulting in a large metacentric chromosome and a very small chromosome with two very short arms
What are acrocentric chromosomes?
chromosomes which have small short arms
Give the 5 acrocentric chromosomes:
13, 14 15, 21 and 22
When is quantitative fluorescent PCR used?
Urgent situations
Describe how quantitative fluorescent PCR works:
a DNA sample is targeted for important aneuploidies using markers for abnormal dosage and paternal and maternal material is compared by capillary electrophoresis
What two methods can result in mosaicism?
1) mitotic non-disjunction
2) trisomy rescue
What is trisomy rescue?
genetic phenomenon in which a fertilized ovum containing three copies of a chromosome loses one of these chromosomes to form a normal, diploid chromosome complement
What are isochromosomes?
a chromosome made out of two long or short arms
What genetic disorder is caused by mosaic tetrasomy of the 12p isochromome?
Pallister-Killian syndrome
Give two characteristics of Pallister-Killian syndrome:
1) intellectual deficit
2) seizures
