3 More Stories from the Genetics Clinic Flashcards
Q: What are the 5 levels of genetic organisation?
A: DNA, gene, chromosome, genome, transcriptome (way in which it’s expressed- regulatory factors can affect)
Q: What is genomic imprinting? Affects? Inheritance? Type of modification? Mechanism?
A: -phenomenon whereby gene expression depends on which parent you inherit it from
- affects around 75 known genes in humans
- non mendelian inheritance
- (no change in genetic sequence) rather it is a reversible epigenetic modification = occurs at level above genetic sequence itself
- DNA methylation is the mechanism: if it occurs at enough points in a certain region -> can switch off expression of gene
Q: What is DNA methylation? Enzyme? Source of methyl group? Only occurs where?
A: -Addition of a methyl group by an enzyme to the 5’ position of the pyrimidine ring of a cytosine to make methylcytosine
- DNMT is DNA Methyltransferase
- SAM is S-Adenosyl Methionine
- humans at CpG dinucleotides
Q: How do we know that the parental origin of the chromosomes is important?
A: 46, XX where genome is from only one parent - rare genetic event where the zygote has chromosomes from only one parent (Uniparental disomy- iso_ if chromosomes are identical). You’d think that as they have a full set of chromosomes you’d get a normal child but you don’t (have problems)
THIS SHOWS THAT THERE IS SOMETHING VERY IMPORTANT IN THE GENOME WHICH ISN’T THE SEQUENCE
Q: What are CpG sites?
A: regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5’ → 3’ direction
Q: What does methylation in the promoter of a gene do? Underlying principle of?
A: represses gene transcription
imprinting and X-inactivation (When the X is inactivated it is HYPERMETHYLATED)
Q: How do methylation patterns vary? Affected by? Potentially?
A: Methylation patterns vary between tissues and vary depending on age.
Methylation patterns are affected by the environment.
DNA methylation patterns are potentially heritable.
Q: Chr 15 imprinting disorders. Name 2 distinct clinical syndromes. What causes both? Difference?
A: -Prader-Willi Syndrome
-Angelman Syndrome
loss of function of one of the two parental chromosomes. Whether you get Prader-Willi or Angelman depends on whether the maternal or paternal chromosome loses function:
- Paternal = Prader-Willi
- Maternal = Angelman
Q: What are the symptoms of Prader-Willi Syndrome? (6) How are these symptoms managed? (4)
A: -Hyperphagia (can lead to obesity)
- Mental Retardation
- Hypotonia (decreased muscle tone)
- Short Stature (and Small Hands and Feet)
- Delayed/Incomplete Puberty
- Infertility
- Hyperphagia managed by diet restriction
- Exercise to increase muscular mass
- Growth hormone treatment for short stature
- Hormone replacement at puberty
Q: What are the symptoms of Angelman Syndrome? (6) Treatment? (3) Lifespan?
A: -Severe Developmental Delay
- Poor or Absent Speech
- Gait Ataxia (lack of voluntary coordination of muscle movements)
- ‘Happy Demeanour’
- Microcephaly
- Seizures
Treatment is Symptomatic:
- Anti-Convulsant
- Physiotherapy
- Communication Therapy
NOTE: People with Angelman have a normal lifespan.
Q: What is the genetic mechanism of Prader-Willi Syndrome? 3 paths?
A: lack of a functional paternal copy of the PWS critical region on 15q11-q13
- 70% due to microdeletion of the critical region on the paternal chromosome (have maternal but maternal is not expressed)
- 25% due to inheritance of two maternal copies by uniparental isodisomy (despite being correct, both are switched off and not expressed)
- 5% due to other mechanisms such as translocations/ imprinting centre defect
Q: What is the genetic mechanism of Angelman Syndrome? (3)
A: microdeletion of maternal allele
uniparental disomy = two paternal copie
Translocation problem/ imprinting center defect in 15q11-q13
Q: What is uniparental isodisomy? Caused by? Explain using PW syndrome.
A: Ending up with a zygote that has a pair of chromosomes from one parent not both.
Caused by non-disjunction in meiosis II.
You end up with three copies of Chr 15 which would be fine if you deleted one of the copies. But if you delete the paternal copy you end up with only maternal copies and hence have Prader-Willi Syndrome.
It is caused by the failure to separate the chromosomes in meiosis II and the failure to remove the correct chromosome following the non-disjunction.
Q: Describe molecular diagnosis (2 methods).
A: FISH - fluorescently labelling regions on chromosomes
An alternate way of doing this is using methylation-specific PCR
Q: What’s the size of the mitochondrial genome? Shape? How many genes does it encode? Copies per mitochondrion? Estimated mitochondria per cell?
A: -16.6kb
- Circular Genome
- 37 genes: 13 respiratory complexes, 22 tRNA, 2 rRNA
- 2-10
- 2-2500
