Quiz Flashcards
When does crossing over happen?
Meiosis 1- in prophase 1
Describe what happens in mitosis
IN prophase chromosomes duplicate
In metaphase align in single row down centre
In anaphase sister chromatids separate–>daughter cells x 2 with full single copy of genetic material
Describe what happens in meiosis
In meiosis I, there is crossing over during prophase 1
IN metaphase 1, the chromosomes align in PAIRS down the centre of the cell like noahs ark
In anaphase the pairs are separated but sister chromatids stay together. Haploid cells created
In meisosis 2 the sister chromatids separate so that each of the FOUR cells has half a full set of chromosomes.
What is the role of rRNA and tRNA?
involved in protein synthesis (translation)
directly for ribosomal RNAs or transfer RNAs
What are introns and exons?
Introns between exons
Exons code for protein
Why might someone be “mutation negative” even though have the disease?
Mutation in promotor region.
Features of Kleinfelters
MOST COMMON CAUSE OF PRIMARY MALE HYPOGONADISM
Low testosterone
Infertility, incomplete virilisation, gynaecomastia
Tall
Mild learning difficulties, immature, shy
Turners describe
Short Widely spaced nipples NORMAL intellect BICUSPID aortic valve and COARCTATION Web neck Infertility, ovarian dysgenesis
Why is it called a microdeletion syndrome?
Have to delete 3-5 million base pairs before see on karyotype.
Is it worse to inherit myotonic dystrophy from mum or dad?
Mum
Trinucleotide repeat
Mum Did it
Is it worse to inherit HD from mum or dad?
Dad
What are the three major players in gene regulation?
Methylation
Histone modification
Non coding RNA
If you methylate a promoter region, what happens?
Gene silenced
What is the mechanism of imprinting?
Methylation of CpG rich domains and modification of histone proteins
True or false, imprinting is reset during gamete formation?
True
Defect in prader-Willi
Loss of paternally active 15q gene copy -either both 15qs are maternal (maternal UPD), or deletion on paternal 15 (most), and a minority from IMPRINTING
How do you get Angelman syndrome?
Deltion of maternal 15q12 (most)
Paternal UPD
UBE3A mutation
Imprinting defects
How/what mechanism with gametes produces UPD?
“rescue” mechanism when zygote is formed with accidentally having three chromosomes after NON-DISJUNCTION- and one is thrown out.
Best way to detect mosaicism
Microarray or next gen sequencing
What is the significance of SNPs?
1 in 300 bases is polymorphic
Usually in non coding regions
Can indicate susceptibility to disease, response to drugs, susceptibility to infection
Warfarin metabolism is often dictated by SNP pattern
Cytogenetics is to what as molecular cytogenetics is to what?
Karyotype
FISH or molecular karyotype
Fish is still used for looking at balanced rearrangement but otherwise replaced by chromosomal microarray
What do red and green mean on a chromosomal microarray?
Green means loss material
Red means gain of material
What does SNP microarray not detect?
Balanced rearrangements Whole or partial gene deletions Triplet expansion Sequence changes Methylation changes
What does next gen sequencing do?
Sequences the whole genome
More economical than individual gene sanger sequencing
CANNOT DETECT trinucleotide repeat or methylation defects
What type of problem is most likely to cause a disease that could be found by classic linkage analysis?
Protein truncating variant.
Describe the problem in BCR-ABL?
BCR originally on 22, ABL originally on 9. Translocation so that BCR next to ABL on chromosome 22.
How do you work out carrier frequency?
square root of (disease frequency/4)
How do you work out disease frequency?
Carrier squared then times by 4
What does the Hardy Weinberg Equation say?
p^2 + 2pq + q^2 = 1 where p is the frequency of one allele and q is the frequency of the other. When multiply it out-
pxp is the number of people homozygous for p, 2pq is the proportion of people heterozygous, and q x q is the number of people homo for q.
What percentage of genes are shared with first degree, second degree and third degree relative?
50%
25%
12.5%
What is Lyonisation?
Another term for X inactivation where in females only one chromosome is doing anything from early on in development. Happens randomly so all females are mosaic. If skewed, female carrier can manifest the condition of their X non inactivated. ie protect from X linked dominant or cause X linked recessive expression
Two examples of X linked dominant?
Rett syndrome
X linked hypophosphataemic rickets
Pedigree pattern: imprinting
Seems to skip some generations
All affected kids are from either only a man or only a woman
Otherwise autosomal so 50% chance of passing on
If it’s a paternally imprinted mutated gene, what do you expect?
none of the children of the male will be affected
half of the children of the female will be affected
Can you use maternal mutant load when assessing mitochondrial disorder to predict risk for fetus?
No. Not all mitochondria are replicated to daughter cells during oogenesis. No way to predict.
Some cells have the mutated mitochondria, others do not. Called-
Heteroplasmy.
Pedigree with mitcohondrial inheritance
All maternally inherited
Males and females affected just as commonly
What is linkage disequilibrium?
Where there is a tendency for genes to be inherited together in a non random fashion because close together in chromosomal position- unlikely to be separated by crossing over at meiosis. Note HLA types not causing disease but just going along for the ride
What does the 2/3 rule say?
If unaffected sibling of someone with an AD disorder, 2/3 chance that you are a CARRIER, 1/3 chance that you are non disease non carrier.
Note does not apply if sibling not affected.
How many CAG repeats in HTT gene before fully penetrant?
40
But Cannot use the number of repeats to predict phenotype with accuracy
Most common heart defect in Downs syndrome
VSD
then endocardial cushion defect>PDA>ASD>TOF
Marfan clinical features
Tall stature Joint hypermobility Aortic dissection, AR/MR Pectus carinatum over excavatum Lens dislocation up Flat foot
Mutation in marfan?
FBN1 mutation
AD
Some disease associations with Down’s
Hypothyroid Coeliac Leukaemia AA instability Dementia
How many copies of CGG repeat until fragile X expression?
200 copies
What is the best way to tell the difference between mitochondrial transmission and X linked?
Same severity of disease in males and females affected in mitochondrial.
Advanced maternal age increases the risk of what?
Non disjunction
Advanced paternal age increases the risk of
some AD diseases like achondroplasia
What does helicase do?
Unwinds the dsDNA
What is the direction of replication of DNA polymerase?
Has to add 5 prime to 3 prime. This means the lead stand starts with 3 prime as the template.
Needs an RNA primer to start it off.
How do transcription factors work?
Regulate binding of RNA polymerase
How do small interfering RNAs work to regulate gene expression?
Enhance breakdown of mRNA
