principles genetics Flashcards
what is a missense mutation
change of amino acid sequence
what is a nonsense mutation
new termination code
what is a silent mutation
no change of the amino acid sequence
what is a frameshift mutation
addition or deletion of a base
what kind of mutation is sickle cell anaemia
missense
what type of inheritance is sickle cell anaemia
co-dominant
what is klienfelters syndrome
3 sex chromosomes (47 XXY)
what is haemophilia A a genetic deficiency of
clotting factor VIII
what kind of inheritance is haemophilia A
X linked recessive but can be spontaneous mutation
are histones positively or negatively charged
positive
what is the DNA cycle
G1 - S - G2 - M - G1
what does mitosis produce
2 identical diploid daughter cells
what does meiosis produce
4 nonidentical haploid daughter cells
where does variation in meiosis come from
crossing over
independent assortment of homologous chromosomes
what occurs in G1
cell growth
when can mutation occur in the cell cycle
between G2 + M and GI + S
what / when is G0
between G1 and S
when cell functions normally and doesn’t replicate - most of life
when does DNA synthesis and replication occur
S phase
S for synthesis
what occurs during G2
DNA replication checked
2nd growth phase - involving proteins etc
what occurs during M
mitosis
m for mitosis
what can you see with Karyotyping
deletions of >5 million base pairings
looks at chromosomes as a whole
what is transcription
DNA to RNA
what is translation
RNA to protein
what are SNPs
single nucleotide polymorphisms
sequence changes in DNA between genes
what is a polymorphism
any variation in a human genome which has a population frequency of >1%
doesn’t cause disease in its own right but may predispose to a common disease
what is a mutation
DNA variant that causes or predisposes to a specific disease
any inheritable change in the human genome
what is a multifactorial disease
multiple polymorphisms cause a risk of disease - combine with environmental factors to cause disease
genes involved will have low penetrance
what is balanced chromosome rearrangement
translocation - usually normal
same amount of genetic information swapped - all chromosomal material is present
what is unbalanced chromosome rearrangement
translocation
extra or missing chromosomal material
usually 1 or 3 copies of some of the genome
what happens to the child if a parent has balanced chromosome arrangement
child inherits normal 2 copies + balanced = 3 copies
what is an acrocentric chromosome
centromere located very near the end of the chromosome
what is a telocentric chromosome
centromere located at terminal end of chromosome
what is epigenic variation
functional modifications to the genome that don’t involve a change in nucleotide sequence
what is aneuploidy
whole extra or missing chromosome
what is translocation
rearrangement of chromosomes
what is reciprocal translocation
segments from 2 different chromosomes have been exchanged
what is monosomy
missing chromosome from a pair
what is trisomy
extra chromosome in a pair
what is down syndrome
trisomy 21
47 XY
3 copies of 21
what can trisomy 14 cause
miscarriage
what is edward syndrome
trisomy 18
what is turner syndrome
one sex chromosome
45 X
what is robertsonian translocation
2 accrocentric chromosomes attach at centromere
only occurs with 13 14 15 21 22
what is the most sensitive technique for looking for chromosomal imbalance (absent or duplicated material)
microarray CGH
can also find polymorphisms
if patient has extra DNA - predominantly red
what is the best technique for looking for point mutations
PCR
what is the best technique for looking at lots of genes
Next generation sequencing
what is the best method for detection of plasma viral load in HIV patient
PCR
what is the best method for measurement of T lymphocytes in blood
immunophenotyping
what is the term to describe the presence of 2+ populations of cells with different phenotypes in one individual
mosaicism
what is gonadal mosaicism
2 populations of cells in gonads one with a DNA mutation or chromosome anomaly
what is somatic mosaicism
it is within the body cells so not passed on to children
post-zygotic mutation
what genes stop cells dividing when switched on
tumour suppressors
what genes start cells dividing when switched on
oncogenes
what is cancer
mutations in a cell cause damage to control genes that allow cell to divide in uncontrolled fashion
normally atleast 3 different groups of cell with different phenotypes
what is penetrance
the likelihood of having a disease if you have a gene mutation
what is the term to describe variation in disease severity if you have the mutation
expression
what are the mutations in CF
CFTR mutation
- F508 deletion
- G551D mutation
what is the carrier frequency of CF
1/24 / 1/25
what is the function of the CFTR gene
channel across membranes that produce mucus, sweat, saliva, tears, digestive enzymes
transports chloride ions out of the cell which indirectly controls the water movement allowing for thin free flowing mucus
what happens when there are mutations in the CFTR gene
sodium is not pumped out into lumen/digestive/respiratory passages so mucus is think as water doesn’t enter areas
what do mutations in the promoter and splice sequences cause
stop transcription or cause abnormal splicing
what do base changing mutations cause
change in amino acid sequence
change in protein sequence
may / may not reduce protein function
what is a mendelian disorder
a disease that is caused by a change in a single gene
what diseases are considered mendelian
autosomal dominant autosomal recessive X links X inactivation mitochondrial
where is the disease seen in autosomal dominant
disease seen in all generations
what is the risk of having an affected child in autosomal dominant
50%
where is the disease seen in autosomal recessive
only one generation affected
if both parents are carriers of an AR disease what is the chance a child will be unaffected not carriers and unaffected affected carrier
unaffected - 3/4
unaffected and not carriers - 1/4
carrier - 1/2
affected - 1/4
what do AR diseases usually cause
loss of function
are X linked diseases recessive or dominant
recessive
if a mother is a carrier of an XL disease what are the chances the daughter will also be a carrier
50%
if a mother is a carrier of an XL disease what are the chances her son will be affected
50%
what is X-inactivation
a cell only requires one working copy of the X chromosome so in females each cell has a random X chromosome inactivated
a woman who is a carrier of a X linked haemophilia experiences haemorrhage following surgery
what is the most likely mechanism
normal X inactivation
50% of cells will have had normal X deleted so reduced capacity for blood clotting
the following s/s are s/s of what myopathy diabetes deafness optic atrophy stroke like episodes encephalitis
mitochondrial disease
mitochondrial diseases are inherited almost exclusively maternally
true/false
true
what is the term for the mutation where there is only one working copy which is not enough
haploinsufficiency
what is the term for the mutation where an abnormal protein interferes with normal protein
dominant negative
what is the term for the mutation where it activates a gene
gain of function mutation
what happens when a polymorphism occurs in the promotor regions
less protein
mendelian disorders have a high penetrance
true/false
true
what does DNA methylation lead to
modification of histones which strengthens binding and so represses transcription
what are 3 examples of non-mendelian inheritance
imprinting
angelman syndrome
heteroplasmy
what is imprinting
differences in gene expression depending on whether a gene is maternally or paternally inherited
what causes angel man syndrome
chromosome 15 fault
mother’s UBE3A works but fathers is methylated
how does angel man syndrome express itself in the phenotype
neuro-genetic disorder developmental delay intellectual disability ataxia epilepsy happy demeanour frequent laughing and smiling
what is heteroplasmy
different daughter cells contain different proportions of mutant mitochondria
what are 5 characteristics gained by cells on progression to cancer
Evasion of immune response Acquire a vascular supply Metastasis Avoid apoptosis Proliferation
what is Li Fraumeni syndrome
mutation in p53 gene resulting in defective p53 protein
what stage of the cell cycle may p53 halt in low O2
G2
give 3 mechanisms of gene activation
duplication of the gene
activation of the gene promoter
change in amino acid sequence
what does FISH stand for and what is it used for
Fluorescence in situ hybridisation
can light up a specific bit of chromosome if you know what bit to look for
can help identify aneuploidy or translocations etc
mutations in BRCA1/2 gene cause a small proportion of what cancers
familial breast/ovarian cancer
what is the BRCA1/2 gene involved in
DNA strand repair
Philadelphia chromosome can cause leukaemia. what does it involve?
9 to 22 translocation
the central dogma involves transcription, splicing, translation and post transcriptional modification
true/false
true
A female patient is short and has mild learning difficulties. She has a lack of monthly periods and is infertile. What condition is most likely?
45X
what is a metacentric chromosome
both arms of the chromosome are the same length
what is the correct symbol for the short arm of a chromosome
p
what disease best fits this phenotype
A female with normal intelligence and infertility
Turner’s syndrome
An individual with the normal number of autosomes, but only one X chromosome
An individual with a balanced translocation between chromosomes 2 and 7, and two X chromosomes
what would the phenotype be
normal female
what is progeria
a rare genetic condition causing growth retardation in infancy with macrocephaly and fast developing signs of old age caused by a spontaneous mutation
