Chromosomal Abnormalities, Sickle Cell, Huntington's Flashcards
What are two methods of prenatal diagnosis?
Chorionic villus sampling
Amniocentesis
What is aneuploidy?
Loss/gain of whole chromosomes –> wrong number of chromosomes
What is an example of a trisomic disorder?
Downs syndrome (chromosome 21)
What is the only example of a monosomic disorder that is viable for life?
Turner syndrome (girls with 1 X chromosome)
What is polyploidy? What is the most common cause for polyploidy?
The gain of a whole haploid set of chromosomes - usually lethal
Fertilisation of egg by more than 1 sperm
What is anaphase lag? What causes it?
Where chromosomes are ‘left behind’ at cell division
Defects in spindle function/attachment to spindle chromosomes
Why is x chromosome monosomy the only example of monosomy that is viable for life? Why are there still problems caused by X chromosome monosomy?
Due to X chromosome inactivation
PAR1 and PAR2 regions need to be active in both chromosomes
What is mosaicism?
The presence of 2 or more cell lines in an individual
What causes mosaicism?
Mitotic nondisjunction
What are two types of chromosome translocations?
Reciprocal translocation
Robertsonian translocation
What is reciprocal translocation?
2 break rearrangements between non homologous chromosomes
What is a robertsonian translocation?
Rearrangement of parts of chromosomes between acrocentric chromosomes
Why do robertsonian translocations result in a chromosome count of 45?
The two p arms of the acrocentric chromosomes fuse together and don’t contain much genetic information and are therefore lost
What is a balanced chromosomal arrangement?
No missing genetic material, just rearranged
What is chromosomal imbalance?
Where there are missing chromosomes or extra genetic material (e.g. Deletions)
How can microdeletions/duplications be identified if they cant be seen by banding at karyotyping?
By using FISH
What is uniparental disomy?
Presence of homologous chromosomes from one parent
What is isodisomy?
2 identical chromosomes from 1 parent
What is heterodisomy?
2 homologous chromosomes from 1 parent
What are imprinted chromosomes? Where can they cause problems?
Chromosomes that show differential gene expression depending on whether they are from the mother or father
During uniparental disomy
How can UPD be generated?
Monosomy rescue
Trisomy rescue
Gamete complementation
Mitotic error
Any 2 of these
What are symptoms of sickle cell anaemia?
Fever
Anaemia
Severe pain
Sudden death
What sort of treatment is used for sickle cell anaemia?
Treatment based on limiting the symptoms
Individuals that are heterozygous for the B-globin mutation that causes sickle cell anaemia will have…
A mild form of the disease called Sickle Cell Trait
Which populations is sickle cell anaemia common in?
African populations
What advantage results from having sickle cell trait?
Individuals are usually resistant to the most lethal forms of malaria
What does epigenetics involve?
Turning genes on or off that code for transcription factors
How can epigenetics be used to treat sickle cell anaemia?
If you can delete the gene that inactivates the gamma-globin gene after birth, there would be increased levels of gamma-globin and decreased levels of beta-globin, minimising the negative effects of sickle cell anaemia
What are the symptoms of Huntington’s?
Abnormal gait
Personality change
Dementia
What type of mutation is seen in Huntington’s? In which gene?
Triplet repeat expansion
HTT gene
How can Huntington’s be tested for?
PCR used to amplify CAG repeats sequence and then separate on gel to determine size
What is the typical age of onset of Huntington’s?
40-50 yrs old
How does Huntington’s develop between generations?
Earlier onset
More severe
What is the relationship between age of onset and the number of CAG repeats?
Earlier age of onset = more repeats
Why can epigenetics not be used to treat Huntington’s Disease?
The HTT gene is switched on in all humans
The inhibition of which pathway was found to prevent Huntington’s Disease in yeast and fruit flies?
The kynurenine biochemical pathway
