Genetics Flashcards
What are the stages of the cell cycle?
G1
S phase
G2
M phase
What happens during S phase?
The DNA is replicated
What happens in G1 phase?
Cells increase in size and the cell contents are duplicated
What happens in mitosis?
One diploid parent produces 2 identical diploid daughter cells
What happens in meiosis?
Gametes are produced
One diploid parent produces 4 haploid daughter cells
What are the parts of a chromosome?
Telomere
Centrosome
Short arm (p)
Long arm (q)
What techniques can be used to analyse chromosomes?
FISH
Array CGH
PCR
NGS - next generation sequencing
What does FISH stand for?
Fluorescent in-situ hybridization
What can FISH be used to determine?
Whether there is extra or missing material
What can NGS do?
Sequence the whole genome or all known exons
What does array CGH do?
Analyses the whole genome BUT cannot detect a balanced arrangement - only unbalanced
The patient’s DNA is compared to a reference sample
What is aneuploidy? - Give examples
A whole extra or missing chromosome
Trisomy 21 = downs syndrome
Trisomy 18 = Edward’s syndrome
What does balanced mean?
All the chromosomes are present however they may be rearranged
What is Robertsonian translocation?
Two chromosomes get stuck together
Note: all the genetic material is still present so there is no disease BUT offspring will be affected
What does trisomy 14 cause?
Miscarriage
What is reciprocal translocation?
When segments of material are exchanged between different chromosomes
This means 50% of offspring will have normal chromosomes or a balanced translocation
The other half will be unbalanced
What is a polymorphism?
A variation in the human genome that occurs in >1% of the population
Therefore it doesn’t cause disease in it’s own right but it may predispose you to specific diseases
What does SNP stand for and what effect does it have?
Single nucleotide polymorphism
Most have no effect
What are CNVs?
Copy number variations
They are extra or missing stretches of DNA
What is a mutation?
A gene change that causes a disease
What are Mandelian disorders?
They are caused by a change in a single gene and are high penetrance
What is penetrance?
The likelihood of having a disease if you have the mutation
What is non-mandelian inheritance? Give examples
Multi-factorial
Methylation and mosaicism
What is mosaicism?
When different cells have different genetic material
A type of Mandelian inheritance is autosomal dominant, what does this mean, for offspring too?
Only one copy of the gene is needed to cause the disease.
Meaning offspring have a 50% chance of getting the disease if parent is affected - so seen in all generations and independent of gender
What does autosomal recessive mean and what does it mean for offspring?
This means two copies of the gene are needed to get the disease.
Meaning the offspring of a carrier has a 25% chance of having the disease if parents are carriers and 50% chance will be carriers.
If one parent has the condition and the other is normal then children 100% chance of being carrier
What is X-linked recessive? (Also Mandelian inheritance)
2 recessive mutations on the X chromosome.
Since males only have one X chromosome they will always have the disease (if mother is carrier), but will never be carriers but can pass onto daughter to be carrier(as need two affected X)
Females will be carriers or affected or fine and will not show major features of disease
What are oncogenes?
Involved in cancer and promote cell division
What are tumour suppressors?
They stop cells dividing
What is methylation and where does it usually occur and what does it do?
The addition of a methyl group.
Occurs on cytosone bases just before guanine bases
Leads to modification of histones that stop transcription
what are the stages in the cell cycle?
G1 -> S -> G2 -> M -> G1
at which stage does DNA synthesis occur?
s phase
define mitosis.
one diploid parent become 2 identical diploid daughters
define meiosis.
on diploid parent become 4 haploid daughter cells
what sequence variation can you get within a gene?
changes in promoter sequence
changes in exon sequence
what sequence changes can you get in DNA between genes?
SNPs
larger deletions or duplications
do polymorphisms cause disease?
no, but may predispose to a common disease
what is a polymorphism?
a genetic variation prevalent in population which, in itself doesn’t cause disease.
what is multifactorial disease caused by?
multiple polymorhisms
what is aneuploidy?
whole extra or missing chromosome
what is translocaiton?
rearrangement of chromosomes
what translocation results in miscarriage?
trisomy 14
what translocation results in Edward syndrome?
trisomy 18
what is a normal male and female?
46XX or 46XY
what is 45X?
turner syndrome
What is 47XXY?
Klinefelter syndrome
what is Robertsonian translocation caused by?
Two acrocentric chromosomes stuck end to end
what is the first line chromosome test?
microarray CGH
what is microarray CGH used for?
to detect any missing or duplicated piece of chromosome and to find polymorphisms
what is mosaicism?
different cells having a different genetic make up (could be a chromosome abnormality or point mutation etc)
What does gonadal mosaicism cause?
a recurrence risk for autosomal dominant conditions even if parent unaffected
what is somatic mosaicism?
all cells suffer mutations as they divide, repair mechanisms exist
what does a tumour suppressor do?
prevent cells dividing
what does an oncogene do?
initiate cell division
what is first line for paediatric referral which checks for deletions/duplications?
aCGH = microarray comparative genomic hybridisation
what do promotor and splice site sequence mutations cause?
Stop transcription or cause abnormal splicing
What will a mutation resulting in changing a base result in?
potentially amino acid change, causing change in protein sequence. May reduce function of protein
what is a mendelian disorder?
an umbrella term for a disease that is caused by a change in a single gene
what is X-linked dominant and how are offspring affected?
One dominant mutation on X chromosome is needed.
So homo and heterozygote dominant females affected (XD XD or XD Xd)
Males be affected.
Males only pass onto daughters (X comes from mother for son)
Females pass equally to offspring.
What type of inheritance is Huntington’s disease?
autosomal dominant
give an example of x-linked dominant disease.
fragile-X- syndrome
what type of inheritance is cystic fibrosis?
autosomal recessive
what type of inheritance is haemophilia?
X-linked recessive
