Clinical Genetics Flashcards
T/F A significant portion of the genome codes for proteins
False, very little of the genome actually codes for proteins
What is the main role of heterochromatin region?
condensing DNA
gene regulation
protect integrity of DNA
What are some of the regulatory products coded by the genome?
tRNA, rRNA, non-coding RNAs
Which process complex is responsible for the splicing of RNA?
Slicesosomes, important for generating diversity
How does histone regulate expression?
it winds more or less tightly via acetylation and methylation, allowing or denying access of replicating machinery
What’s euchromatin?
the open conformation of chromosome (heterochromatin is closed)
What is DNA methylation associated with?
Silencing genes
What is the CpG region also known as?
CpG islands, because they are rich around promotor regions
How is CpG island related to silencing of the genome
when it’s hyper-methylated + low acetylation of histone, the gene is silenced
T/F Euchromatins have hypermethylated CpG islands
False, euchromatins are open, allowing replication. So CpGs are lacking methylation, while histones are hypermethylated
What are some ways of generating genome and protein diversity?
having more than one promotor on one gene
alternative splicing from the same transcript
What are some roles of non-coding RNAs?
act as decoy
scaffold,
guide transcription factor
enhancer
What are short interfering RNAs made from?
double stranded RNAs
What is the action of short interfering RNA
Interact with RNA-induced silencing complex to increase degradation of mRNA
What is the function of micro-RNAs?
interact with RISC to repress translation rather than degrade mRNAs
What is bi-allelic expression?
Where both maternal and paternal copy need to transcribe equal amount of proteins at a time
What is trisomy 21 also known as?
Down syndrome
What are the symptoms of down syndrome?
mental disability
congenital heart disease, GIT disease, increased risk of leukemia, early onset Alzheimer
What is trisomy 18 also known as?
Edwards Syndrome, with severe mental disability, limb and heart defects
What are some autosomal recessive conditions?
cystic fibrosis, sickle cell anaemia, thalassaemia, haemochromatosis
What is haplo-insufficiency?
When there is only one copy of the chromosome and not enough protein is produced.
Autosomal dominant condition
When does X-chromosome inactivation occur?
around 8 cell stage
What is the Barr body?
condensed chromosome on X-inactivation
How does X-inactivation occur?
due to non-coding RNA Xist expression, which creates a wave of hyperchromatin in both directions
What is Turner syndrome?
45X, where one X is missing. There are a few genes that must remain active
Which genes of the inactivated X genes must remain active?
genes that cluster at the ends of the chromosome, homologous to the Y chromosome
What are genomic imprinted genes?
genes that are expressed in parent-specific manner. The maternal and paternal genes come together during fertilisation
What is parthenogenesis and androgenesis?
parthenogenesis = all maternal origin chromosomes androgenesis = all paternal origin chromosomes
T/F Maternal genes tend to conserve resource for the mother
True
What are the four causes of imprint disorders?
large deletion/duplication of chromosomes with imprint genes
Uniparental disomy
Epimutation
DNA mutation
What is uniparental disomy?
extra chromosome from either mother or father
What is Beckwith-Widemann syndrome?
overgrowth due to mostly sporadic epimutation on maternal allele
What is Prader-Willi syndrome?
Overgrowth due to
1) deletion of paternally inherited C15
2) maternal uniparental disomy
What is Angelman syndrome due to?
deficiency in maternally-imprinted genes
What is the first step of prenatal testing?
take a 3 generation family history to look for any inherited condition, recurrent miscarriages, or unexplained perinatal deaths
When does the risk of down syndrome increase in relation to maternal age
30
What is the reason for prenatal testing?
Offer choice in order to help patients make better decisions
What does the first trimester screen involve?
Biochemical test at 10 weeks, ultrasound at 11-13 weeks, and nuchal translucency
What is nuchal translucency?
Fluid behind baby’s neck. Thick fluid is not normal
What does 1st and 2nd trimester screening look for?
Trisomy 21 and 18
Down syndrome and Edwards syndrome
What does the 2nd trimester screening involve?
blood test at 15-17 weeks + maternal age to work out risk algorithm
What is the 2nd trimester a good screening tool for?
neural tube defect
What are the diagnostic tests offered to women with high risk of birth defect?
Chorionic villus sampling at 11 weeks
Amniocentesis at 15 weeks
What does Chorionic villus sampling involve?
insert needle into placenta to get tissue from embryonic placenta
What is fluorescence in situ hybridisation for?
test on the cells collected by CVS and amniocentesis
What are the three ways of analysing collected tissue from CVS and amniocentesis
FISH
Karyotype
Microarray
