genetics Flashcards
1
Q
what is euchromatin
A
DNA+proteins+RNA
2
Q
what is the difference between euchromatin and heterochromatin
A
euchromatin - actively transcribed regions of DNA
heterochromatin - few actively transcribed regions of DNA
3
Q
what bases are euchromatin and heterochromatin rich in
A
euchromatin - rich in GC
heterochromatin - rich in AT
4
Q
which, euchromatin and heterochromatin look light and dark when chromosomes are stained
A
euchromatin - light
heterochromatin - dark
5
Q
explain the replication of euchromatin and heterochromatin during S phase
A
euchromatin - replicate early during S phase
heterochromatin - replicate late during S phase
6
Q
what is the biggest and the smallest proportions of sequence of the human DNA
A
biggest - transposon-based repeats
smallest - protein coding regions
7
Q
what are the functions of the 5’ cap and the poly A tail to an mRNA transcript
A
5’ - helps position the RNA on the ribosome for translation
polyA tail - confer some stability to the mRNA
8
Q
how are introns spliced out of the genome
A
by the splicosome (protein complex of snRNA)
9
Q
how does the splicosome bind exons together
A
recognises the donor and acceptor splice sites
10
Q
what is the difference between a histone and a nucleosome
A
histone - protein
nucleosome - multiple proteins+DNA coiled
11
Q
chromatin remodelling is critical to allow
A
access to the transcription machinery
12
Q
how can histone proteins be modified
A
acetylation of lysine residues
methylation
13
Q
what are the ways which chromatin can be remodelled
A
- acetylation of lysine residues of histones
- methylation of histones
- methylation of DNA
- nucleosome moves along the DNA
14
Q
to go from euchromatin to heterochromatin what must happen
A
chromatin remodelling
15
Q
in what areas of DNA does methylation occur
A
where we have a C next to a G
C is methylated
16
Q
what is the role of methylation of DNA
A
silences the gene
17
Q
CpG regions are associated around which parts of DNA
A
around promoter regions
18
Q
explain the epigenetics of heterochromatin
A
- hypermethylation of CpG of DNA
- low acetylation of histones
- variable methylation of histones
19
Q
explain the epigenetics of euchromatin
A
- hypomethylated CpG of DNA
- hyperacetylation of histones
- variable methylation of histones
20
Q
other than the minimum requirements needed for transcription, what else helps further regulate transcription
A
- DNA looping around itself causing direct interactions of a promoter with other cis-acting DNA sequences (enhancers, silencers)
- ncRNA
- trans-acting proteins
- alternative promoters in a gene
- alternative splicing of a transcript
21
Q
what are the 3 types of non-coding RNA
A
long non coding RNA (lncRNA) short interfering RNA (siRNA) micro RNA (miRNA)
22
Q
what are the 4 functions of long non coding RNA
A
- can act as a decoy and take the RNA polymerase away with it to reduce gene expression
- scaffold to bring in TF (silencing or enhancing gene expression)
- guide (physically interact with the protein to guide the TF or the polymerase to the right spot)
- can affect alternative splicing
23
Q
siRNAs interact with what
A
a protein called RISC (RNA-inducing silencing complex)
24
Q
function of siRNA
A
RISC complexes with the antisense siRNA –> siRNA binds to mRNA that is fully complementary –> causes cleavage of the region by RISC –> specific mRNA degredation and reducing protein production
25
function of microRNA
binds with RISC --> binds to partly complementary mRNA --> causes repression of translation
26
what can cause a regulation of translation
miRNA
27
list the mechanisms used in chromatin remodelling
- histone modifications (acetylation and methylation)
- DNA methylation
- nucleosome positioning
- non-coding RNA
- nuclear location of chromatin
28
how is it possible that we have 20000 genes but many many more proteins
due to:
- many genes have more than one promoter
- alternative splicing
29
the majority of genes have what type of expression
biallelelic - giving 100% protein levels
30
what is the importance of gene dosage
it is important in the regulation of levels of protein expression
31
what is aneuploidy
unbalanced sets of chromosomes due to excess or deficiency of individual chromosomes
32
aneuploidy most often arises due to
non-disjunction of 2 homologous chromosomes or sister chromatids during cell division, either in mitosis or meiosis
33
which trisomy conditions can survive to term
13, 18, 21 and sex chromosome trisomy
34
what causes the abnormal development in trisomy and monosomy conditions
trisomy - because there is 50% increased expression of several critical genes
monosomy - because there is 50% decreased expression of several critical genes
35
which monosomy conditions can survive to term
XO (no autosomal monosomies)
36
trisomy 21 is associated with what
- congenital anomalies of the GIT
- increased risk of leukaemia
- IS defects
- Alzheimer-like disease
37
what is the colloquial name for trisomy 18
Edwards syndrome
38
what are the physical findings of babies with Edwards syndrome
- overlapping fingers
- club (rocker-bottom) foot
- heart defects
- developmental disability
39
what is haploinsufficiency
where having only one normal copy of a gene is not sufficient to support normal cell function
(autosomal dominant inheritance)
40
what is monoallelic gene expression
certain genes MUST by expressed from ONLY ONE copy for normal cell function and development
41
which to mechanisms operate to maintain monoallelic gene expression
```
X chromosome inactivation in females (epigenetic)
genomic imprinting (epigenetic and genetic)
```
42
epigenetic regulation encompasses what
- DNA methylation of promoter regions of genes
- histone modifications - chromatin remodelling
- gene silencing through non coding RNA
43
how can a female be a mosaic for the X chromosome inactivatedq
because the inactivation is random during early foetal development and is passed down along cell lines
44
what is the evidence for some of the genes on the "inactivated" X chromosome still be expressed
Turner's syndrome - if you only have one X chromosome --> syndrome
45
characteristics of Turners syndrome
- short stature
- infertility due to absent or immature gonadal development
- absence of secondary sexual development
- impaired neurocognitive function (visuospatial, perceptual)
46
what is genomic imprinting
the process whereby the parental origin of a particular gene is "marked" by a reversible epigenetic mechanism
47
when does imprinting occur
when gametes are generated the imprints are erased and then re-established according to the sex of the individual
48
what is parthenogenesis and androgenesis
parthenogenesis - whole set of chromosomes from mother
| androgenesis - whole set of chromosomes from father
49
what does parthenogenesis result in
typically non-viable embryos and can lead to ovarian teratomas
50
what does androgenesis result in
typically hydatiform moles which can lead to malignant choriocarcinoma
51
why does parthenogenesis and androgenesis lead to non viable embryos
because the gene dosage of imprinted genes is disrupted
52
what is the parental conflict hypothesis
- maternally expressed genes tend to limit foetal growth (involved in resource conservation and less flow to the foetus)
- paternally expressed genes tend to promote foetal growth (involved in resource extraction to give more energy to the foetus)
53
what are the 4 mechanisms that lead to imprinting disorders (disruption of gene dosage of imprinted genes)
- large deletions or duplications of chromosome regions that contain imprinted genes (LOH)
- uniparental disomy
- alteration in epigenetic marks at imprinted loci without alteration in DNA sequence = epimutation
- DNA mutations in genes that are usually imprinted or in imprinting control centres
54
what is uniparental disomy
where instead of one chromosome coming from each mum and dad - one parent provides both
(leads to a deficiency in one parents genes and a duplication of the others)
55
with epimutation, you end up with what type of gene expression
biallelic
56
what are the 3 common imprinting disorders
Beckwith-Wiedemann syndrome
Prader-Willi syndrome
Angelman syndrome
57
what is associated with a 9x greater risk of a foetus with Beckwith-Wiedemann syndrome
reproductive technologies
58
the majority of Beckwith-Wiedemann syndrome is due to which mechanism of disruption of imprinted genes
epimutation on maternal allele
59
what is responsible for prader-willi syndrome
deficiency of paternally-expressed genes
| microdeletions of paternal chromosome --> LOH
60
what is responsible for angelmann syndrome
deficiency of maternally expressed genes
| microdeletions of maternal chromosome --> LOH
61
explain the inheritance pattern of a mutation in an active paternal gene or inactive maternal gene
- carrier males and affected males can have affected children but not carrier children
- carrier females and affected females cannot have affected children but can have carrier children
62
explain the inheritance pattern of a mutation in an active maternal gene or inactive paternal gene
- carrier females and affected females can have affected children but not carrier children
- carrier males and affected males cannot have affected children but can have carrier children
63
How does X inactivation in females occur
starts with expression of Xist (lncRNA) --> leads to heterochromatin formation spreading outwards along the chromsome. DNA methylation also plays a role
64
which chromosomes are involved in Beckwith-Weidemann syndrome, Prader Willi syndrome and Angelmann syndrome
```
BW = 11
PW = 15
AM = 15
```
65
what percentage of babies have a "birth defect"
~4% in Australia
66
what are the two most common chromosomal defects of live births
trisomy 21
| XXY
67
when taking a family Hx, how many generations should you ideally take
3
68
what proportion of pregnancies have a foetus with a neural tube defect
1 in 500
69
function of prenatal SCREENING
identifies a subset of women from the general population at increased risk of having a child with a birth defect
70
it what stage of pregnancy can you test for neural tube defects
second trimester
71
what is the combined screening in the 1st trimester
- blood taken (9-13 weeks)
- 2 chemical analytes measures (pregnancy associated plasma protein and bhCG)
- ultrasound performed to measure nuchal transluency
72
what is nuchal translucency
thickness of fluid accumulated under the skin at the back of the foetal neck which is measured with ultrasound
73
what is nuchal translucency a marker for
thick oedema is a marker for trisomy 21
74
what are the cut offs for further screening from 1st trimester screening for T21 and T18
```
T21 = 1:300
T18 = 1:175
```
75
what is the screening in the 2nd trimester
blood taken and 4 biochemical analytes measured
76
what are the 4 analytes measured in 2nd trimester screening
bHCG
inhibin A
oestriol
alpha foetal protein (AFP)
77
what are the cut offs for further screening from 2nd trimester screening for T21 and T18 and neural tube defects
T21 = 1: 250
T18 = 1:200
neural tube defects >2.0MoM
78
which screening (1st or 2nd trimester) is better at detecting T21
1st
79
what are the prenatal DIAGNOSTIC tests
chorionic villis sampling
| amniocentesis
80
when is prenatal diagnostic testing performed
offered to women
- with an increased risk screening result
- of advanced maternal age
- who are known carriers
81
at what time of gestation is CVS and amniocentesis performed
```
CVS = from 11 weeks
amniocentesis = 15-16 weeks
```
82
what is CVS
sampling of placental tissue either transabdominally or transvaginally
83
what is amniocentesis
sample of amniotic fluid taken transabdominally
84
what is the risk of miscarriage from CVS and amniocentesis
CVS = ~1%
amnio = ~0.5%
(on top of background risk)
85
what are the two different ways of termination and what are their timings
less than 16 weeks = dilatation and curettage under GA
| more than 16 weeks = prostaglandin induction of labour
86
what tests can you perform on samples taken by CVS or amniocentesis
FISH
PCR
karyotype
chromosomal microarray
87
What is FISH
fluorescence in situ hybridisation
88
what is the advantage of FISH over karyotype, and karyotype over FISH
FISH over karyotype: takes much shorter time period
| karyotype over FISH: can show rearrangements and balanced translocations (more information)
89
what are the 2 ways in which trisomy 21 can occur
- extra whole chromosome (95%)
| - unbalanced translocation between acrocentric chromosomes (5%)
90
what is a Robertsonian translocation
translocation between two acrocentric chromosomes
91
what is an acrocentric chromosome
chromosome basically has no short arm (just a little head)
92
what is the difference in phenotype between someone who has a balanced and unbalanced Robertsonian translocation between chromosomes 21 and 14
```
balanced = carrier
unbalanced = phenotype
```
93
what is the function of microarrays
can look at SNPs and copy number variations (CNVs)
94
what is the first tier test for developmental delay, intellectual disability and autism in Australia
Chromosomal microarrays
95
when is a prenatal molecular karotype recommended
when:
- foetal abnormality is identified on US
- the nuchal translucency measurement is >3.5mm
- a banded karyotype identifies a complex change
- a family member has a microdeletion syndrome and a pregnancy is at risk
96
what is pre-implantation genetic diagnosis
requires IVF
- take one or two cells from a 3 day old dividing zygote and do DNA testing or FISH
- unaffected embryos implanted
97
what is the new alternative to invasive screening tests
non-invasive prenatal testing/NIPT - take maternal blood (will have some foetal DNA in it)
98
what things should you ask when gaining a family history for genetic conditions
- inherited conditions
- Downs syndrome and other chromosomal conditions
- other birth defects
- intellectual disability
- recurrent miscarriage
- unexplained perinatal deaths
- consanguinity
- ethnic background
99
what technology does non-invasive prenatal testing use
massive parallel sequencing technology
100
when is nuchal translucency measured and what is the normal value
between 11-14 weeks
| normal is less than 3mm at this time of gestation
101
what are the results of a first trimester screening test that suggest trisomy 21 and 18
21 - increased hCG and PAPP-A
| 18 - decreased hCG and PAPP-A
102
what other factors are taken into account when calculating a result from combined first trimester screening
womans age at EDD
woman's weight
gestation of pregnancy
(+ blood analytes and nuchal translucency)
103
what is the role of PCR in massively parallel sequencing
it creates a large amount of DNA of interest, enough to produce a detectable signal in a sequencing reaction
