chromosomes week 8 Flashcards
1
Q
what is euchromatin
A
- open structure
- active genes
- the leg bits of chromosomes
2
Q
what is heterochromatin
A
- condensed structure
- active genes
- at ends and centre of chromosomes
3
Q
what are telomeres
A
the bits at the end of chromosomes
4
Q
what direction is DNA synthesised
A
5’ to 3’
5
Q
what does DNA polymerase need to initiate DNA synthesis
A
RNA primer
6
Q
what happens to the lagging strand in DNA replication
A
it is synthesised in fragments (Okazaki fragments) which are stitched together by ligase
7
Q
why do telomeres get shorter as eukaryotes age
A
in the lagging strand the removal of the RNA primer causes a gap which is filled with repeats and is resynthisised by telomerase
- but telomerase is only expressed in certain cell types which is why telomeres shorten
8
Q
what is the centromere
A
- site of kinetochore which is the protein complex that binds to microtubules
9
Q
what happens in S phase
A
DNA replication occurs
10
Q
what percentage of our DNA is protein coding
A
2%
11
Q
what are some extragenic sequences (non-coding)
A
- tandomly repeated DNA sequences (satellite DNA and minisatellite DNA)
- highly repeated interspersed DNA sequences (SINEs - short interspersed nuclear elements and LINEs - long)
12
Q
what is a chromatin
A
DNA packaged with histone proteins forms chromatin
13
Q
what charge do histone proteins have
A
positive charge
14
Q
what are the unit packages in chromatins called
A
nucleosomes
15
Q
what is at the core of the nucleosome
A
eight histone proteins collectively called octameric histone and DNA gets wrapped round this (146bp wrapped 1.8 turns)
16
Q
what are the histone protein types in the octameric histone
A
- histone H2A
- histone H2B
- histone 3
- histone 4
so two of each make the core
17
Q
what does histone 1 do
A
binds to the base of the nucleosome and helps fix the DNA in place
18
Q
what does the wrapping of nucleosomes form
A
- solenoid strucure
- about 6 nucleosomes per turn
19
Q
so what is each bit of the condensed chromatin structure
A
- nucleosome
- chromatin fibre
- fibre-scaffold complex
- chromosome
20
Q
what is the purpose of packaging DNA
A
- negatively charged DNA neutralised by positive charged histone proteins
- DNA takes up less space
- inactive DNA can be folded into inaccessible locations until required
- inactive chromatin characterised by specific histone modification (e.g. methylation)
21
Q
what is the shorter arm on a chromosome called
A
p or petite arm
22
Q
what is the longer arm on a chromosome called
A
q arm
23
Q
what is a metacentric chromosome
A
where centromere is close to being in the middle
24
Q
what is a submetacentric chromosome
A
where centromere is displaced from centre
25
what is an acrocentric chromosome
the centromere is so far displaced that the petite arm contains no functional DNA
26
what is a karyotype
A karyotype is a preparation of the complete set of metaphase chromosomes sorted by length, centromere location and other features.
27
what is chromosome analysis
- blood taken
- remove red cells (no nucleus)
- culture white cells
- incubate
- colchicine added (mitotic inhibitor)
- separate off white cells
- saline added
- stain
- photograph
28
what is fluorescent in situ hybridisation (FISH)
a more detailed way of looking at specific chromosome sequences
sequence of interest labelled with fluorescent dye
29
what is meiosis
- cell division in germ cells
- diploid cells (ovaries/testes) divide to form haploid cells
- chromosome are passed on as re-arranged (recombined) copies
30
what is oogenesis
process of egg formation
31
what is spermatogenesis
process of sperm formation
32
when does gametogenesis happen in males and females
females - early embryonic life cells arrive at meiosis 1 and then at puberty cells go through meiosis 2
males - puberty
33
what is X inactivation
random inactivation of one X chromosome in females
34
what are the different types of chromosomal abnormalities
- numerical (wrong number)
- structural (scale rearrangement that's apparent from karyotype)
- mutational (smaller scale - can range from small deletions to point mutations)
35
what is the most common type of abnormality in first trimester miscarriages
trisomy (think tri=trimester)
36
what is trisomy mutation
where there are three copies of a chromosome when there should only be two (so in total 47 chromosomes)
37
what is monosomy X
there is only a single sex chromosome (so 45 chromosomes total)
- first trimester miscarriages
38
what is triploidy mutation
where there are three whole copies of chromosomes (so 69 chromosomes)
- first trimester miscarriages
39
what is tetraploidy mutation
there are four copies of chromosomes (so 92 total)
| - first trimester miscarriages
40
what are common chromosomal abnormalities in lovelorn infants
- trisomy 13
- trisomy 18
- trisomy 21 (down's)
- 45 X
- 47 XXY
- 47 XYY
41
what is trisomy 13
patua's syndrome
| - 47 XX
42
what is trisomy 18
Edward's syndrome
| - 47 XY
43
what is trisomy 21
Down's syndrome
| - 47 XX
44
what is 47 XXY
Klinefelter
45
what is monosomy 45X
turner
46
what is an autosome
non-sex chromosome
47
are sex chromosome abnormalities often from maternal or paternal origin
paternal
| - 45X
48
are autosomal abnormalities more often from maternal or paternal origin
maternal
| - trisomy 21
49
down's syndrome
- trisomy 21
- 1 in 650
- IQ can be less than 50
- Alzheimer's later in life
- facial dysmorphologies
50
patua syndrome
- trisomy 13
- 1 in 5000
- multiple dysmorphic features and mental retardation
- few survive beyond first year
51
Edward's syndrome
- trisomy 18
- 1 in 3000
- severe developmental problems, most patients die within first year, many within first month
52
turner syndrome
- 45 X
- 1 in 5000 to 1 in 10,000 (liveborn)
- incidence at conception much greater but 97% result in spontaneous loss
- female of short stature and infertile
- neck webbing and wide spaced nipples
- intelligence and lifespan normal
53
klinefelter syndrome
- 47 XXY
- 1 in 1000
- tall stature and long limbs
- male but infertile
- small testes
- 50% gynaecomastia (man boobs)
- mild learning difficulties
54
what are the different types of structural abnormalities
1. balanced or unbalanced rearrangements
2. translocations (reciprocal or robertsonian)
3. deletions
4. insertions
5. inversions
55
what is a translocation mutation
where material is exchanged between two chromosomes
56
what are the two types of translocation mutations
1. reciprocal - involving breaks in two chromosomes, these broken segments swap and so info exchanged
2. robertsonian - fusion of two Acrocentric chromosomes
57
when is a reciprocal translocation said to be unbalanced
when there is additional DNA or DNA mission
- so i.e. more from dad than mum when it should be equal
- this can result in partial trisomy and partial monosomy in the same cell because only one and a half chromosomes from mum and two and a half from dad
58
what happens in a robertsonian translocation
- two Acrocentric chromosomes fuse
- loss of short arms (which have no coding DNA anyway)
- this can result in trisomy/monosomy
59
who has a predisposition to having children with Down's syndrome
individual with robertsonian translocation
60
what is paracentric inversion
inversion of bit of chromosomal arm
61
what is pericentric inversion
inversion of centromere
62
what are some types of genetic mutations
1. non-coding
2. coding
- silent - CGA (Arg) to CGC (Arg)
- missense - CGA (Arg) to GGA (Gly)
- nonsense - CGA (Arg) to TGA (stop)
- frameshift (deletion/insertion)
63
what is Cys64Arg
a cystine changed to an arginine at position 64
64
what is M252X
methane 252 and X means stop codon
65
what is 1294del40
amino acid 1294 deletion of 40
66
what is 662-42C>T
the closest ending exon position is 662 and so 662-42 because it is 42 nucleotides before this
67
what is IVS2+12insG
intervening sequence 2 so that will be the second intron in the +12 position within that intervening sequence and we have insertion of a G
68
what techniques can you use to detect mutations
- PCR
- gel electrophoresis
- restriction fragment length polymorphism (RFLP)
- amplification refractory mutation system (ARMS)
- DNA sequencing
69
what do you need for PCR
- sequence information
- oligonucleotide primers
- DNA
- nucleotides
- thermoresistant DNA polymerase
70
what are the steps in PCR
1. denature 93-95 degrees
2. anneal (heat then cool) 50-70 degrees
3. extend using DNA polymerase to add nucleotides
70-75 degrees
71
what is gel electrophoresis
- separating DNA fragments by size by applying an electric field
- you do this after PCR
72
what is amplification refractory mutation system (ARMS)
- type of PCR
- if you use normal primer with normal nucleotide then DNA will be amplified with the help of a constitutive primer
- if you use mutant primer with normal nucleotide no DNA amplification (e.g. A-G not work)
- mutant primer with mutant nucleotide will work (e.g. A-T works)
73
what are restriction endonucleases
- enzymes from bacterial cells
- protective mechanism
- degrade DNA of invading viruses
- recognise specific DNA sequences
- usually recognises 4-8bp
- always cuts DNA at same site
74
what is RFLP analysis
so restriction enzyme can recognise and cut normal DNA but it cannot recognise mutant DNA
- simple and cheap
75
what is DNA sequencing
- chain termination method
- use of dideoxynucleotides
- there is a H group at the three prime position of the carbon ring instead of OH
- expensive
