Chromosomal Abnormalities Flashcards
(120 cards)
1
Q
How do you prepare a karyotype? (7)
(Big White Polar bears Will Kill Some Guys
A
- Collect heparinised venous blood
- Isolate white cells
- Culture in phytohaemagglutinin —> T cell growth
- Wait 48 hrs
- Add colchicine —> mitotic arrest
- In hypotonic saline on slide
- Fix and stain (giemsa)
Big —> Blood
White —> White cells
Polar bears —> Phytohaemagglutinin
Will —> Wait
Kill —> Colchicine
Some —> Saline
Guys —> Giemsa
2
Q
What is a karyotype?
A
Visual representation of a cell’s chromosomes in order
3
Q
Which stain is used for karyotypes?
A
Giemsa
4
Q
What is the telomere?
A
Ends of a chromosome —> repetitive DNA sequence
5
Q
What is the centromere?
A
Centre of chromosome —> sister chromatids join
6
Q
What is the p-arm?
A
Short arm (top arm)
7
Q
What is the q-arm?
A
Long arm (bottom)
8
Q
Why is gisema staining used for chromosomes?
A
Leaves banding pattern
- Light —> more stain —> euchromatin
- Dark —> less stain —> heterochromatin
9
Q
What are G-dark regions of chromosomes?
A
Dark bands (heterochromatin)
10
Q
What are G-light regions of chromosomes?
A
Light bands (euchromatin)
11
Q
What are the 4 parts of a chromosome?
A
- 2 Telomeres
- Centromere
- P arm
- Q arm
12
Q
How are bands numbered?
A
_ _ . _
1. Band
2. Sub-band
3. Sub-sub-band
- eg. 31.2 —> Band 3, sub-band 1, sub-sub-band 2
13
Q
What do G-dark bands contain?
A
Heterchromatin
14
Q
What do G-light bands contain?
A
Euchromatin
15
Q
What is bphs?
A
Bands Per Haploid Set
16
Q
What is the difference between heterochromatin and euchromatin?
A
- Hetero —> more compact, fewer genes
- Eu —> more open, more genes
17
Q
When is a karyotype usually taken?
A
Prophase
18
Q
What is the human genome project?
A
Research project that mapped and understood all human genes
19
Q
What is whole genome sequencing?
A
Method to determine complete DNA sequence of an organism
20
Q
When is whole genome sequencing done?
A
- Cancer patients
- Children with suspected abnormality
21
Q
What does ‘pter’ mean in chromosome nomenclature?
A
End of p-arm (terminal)
22
Q
What did whole genome sequencing lead to the discovery of?
A
50-60 New genetic diseases
23
Q
What does ‘qter’ mean in chromosome nomenclature?
A
End of q-arm (terminal)
24
Q
What does ‘cen’ mean in chromosome nomenclature?
A
Centromere
25
What does 'del' mean in chromosome nomenclature?
Deletion
26
What does 'der' mean in chromosome nomenclature?
Derivative chromosome (contains extra material)
27
What does 'dup' mean in chromosome nomenclature?
Duplication
28
What does 'ins' mean in chromosome nomenclature?
Insertion
29
What does 'inv' mean in chromosome nomenclature?
Inversion
30
What does 't' mean in chromosome nomenclature?
Translocation
31
What does +/- before the chromosome number mean?
Gail/loss of whole chromosome
32
What does +/- after the chromosome number mean?
Gain/loss of part of the chromosome
33
What can giemsa staining detect?
Chromosomal abnormalities via karyotype
34
What are the 2 types of chromosomal abnormalities?
1. Aneuploidy
2. Structural abnormalities
35
What is aneuploidy?
Abnormal number of chromosomes
(more/less than 2 of a homologous pair ---> more/less than 46)
36
What are the 2 types of aneuploidy?
1. Monosomy ---> 1
2. Trisomy ---> 3
37
What is trisomy?
Gained one extra copy of a particular chromosome (3)
38
What is monosomy?
Missing one copy of a particular chromosome (1)
39
What is the purpose of meiosis?
Reduction from diploid to haploid ---> ensure genetic variation
40
How does meiosis create genetic variation? (3)
1. Random assortment
2. Crossing over
3. Recombination
41
How does aneuploidy arise?
Non-disjunction
42
Which daughter cells are effected if non-disjuntion occurs in meiosis II?
Only 2
43
Which daughter cells are effected if non-disjuntion occurs in meiosis I?
All 4
44
What types of aneuploidy does non-disjunction always result in after fertilisation?
Monosomy or trisomy
45
What is the most common form of aneuploidy?
Sex chromosome aneuploidy
46
What is the prevalence of sex chromosome aneuploidy?
1. 1/400 males
2. 1/650 females
47
Why may X chromosome aneuploidy be tolerated?
X-inactivation of excess X chromosomes (only 1 active)
48
Why may Y chromosome aneuploidy be tolerated?
Low gene content of Y chromosome
49
What is the PAR of sex chromosomes?
Pseudo-autosomal region
- Influence non-sex traits eg. immune system
50
Why does sex chromosome aneuploidy still have some effect even when the extra chromosome is inactivated? (2)
PAR in X and Y needed
51
When does X chromosome aneuploidy cause an effect? (3)
1. Division of odd number ---> not tolerated
2. Not all excess X chromosome inactive
52
What is an example of aneuploidy?
Trisomy 21
53
What does trisomy 21 cause?
Down's Syndrome
54
What is the karyotype of individuals with trisomy 21?
47 + 21
55
How does trisomy 21 usually arise?
Maternal non-disjunction
56
What is maternal age effect?
Correlation between mother age and effects on offspring
57
What is the maternal age effect of trisomy 21?
Older mum ---> more likely trisomy 21 child
58
What is oogenesis?
Development of ovum in ovaries
59
When is oogenesis completed?
Fertilisation
60
What are the 3 stages of oogenesis?
1. Oogonium mitosis ---> primary oocyte
- Baby in utero
- Paused in prophase I till puberty
2. Oocyte meiosis I ---> secondary oocyte + polar body
3. Oocyte meiosis II ---> ovum + polar body
- Paused in metaphase II ---> ovulation
- Completed if fertilised
61
Why does an increased maternal age increase the risk of trisomy 21 specifically?
Increased risk of maternal non-disjunction
62
How many mitotic divisions occur to primary spermatocytes per year?
23
63
What is the paternal age effect?
Correlation between father age and effects on offspring
64
Why does an increased maternal age increase the risk of some gene disorders?
Degradation of factors holding homologous chromatids together over time ---> chromatids don't align at mitotic equator
65
What do egg and sperm cells start as?
1. Egg - oogonium ---> oocyte
2. Sperm - spermatogonial stem cells ---> spermatocyte
66
What are the products of the 2 divisions of a primary oocyte?
Ovum + 3 polar bodies
67
Is there a paternal effect on aneuploidy?
No
68
Which disorders have a paternal age effect?
Single gene disorders
69
What are 3 examples of gene disorders with paternal age effect?
1. RET
2. FGFR2
3. FGFR3
70
Which 3 gene mutations have a paternal age effect?
1. Pfeiffer
2. Apert
3. Crouzon
71
What enhances the paternal age effect?
Selfish spermatogonial selection
72
What does selfish spermatogonial selection refer to?
Certain mutations have a selective advantage to the spermatogonial stem cells
73
What is a paternal risk factor for aneuploidy?
Smoking
74
What proportion of still births and spontaneous abortions are a result of aneuploidy?
- 5% of still births
- 50% of spontaneous abortions
75
How prevalent is aneuploidy?
5% of all pregnancies
76
When can trisomy of any chromosome be detected?
Prenatally
77
Why does trisomy often lead to still births or spontaneous abortions?
Most not compatible with life
78
Which 3 trisomies are compatible with life?
1. 21
2. 18
3. 13
79
Is aneuploidy usually compatible with life?
No
80
What is genetic mosaicism?
Presence of populations of cells with 2 or more different genotypes
81
What proportion of the population is thought to have genetic mosaicism?
100% ---> everyone
82
What are the 2 causes of genetic mosaicism?
1. Non-disjuncture in early development
2. Loss of extra chromosome in early development
83
What can mosaicism in aneuploidy lead to?
Lethal aneuploidy becoming survivable
- eg. Trisomy 8 or 9
84
What are the most common genetic mosaics?
45, X
85
When does crossing over occur?
Prophase I of meiosis
86
What are the 2 stages of crossing over?
1. Pairs of chromosomes align
2. Chiasma forms ---> cross over
87
How many times does crossing over occur per chromosome per meiosis?
1-3
88
What does crossing over increase?
Genetic diversity
89
What is a chiasma?
Location of chromatids crossing over
90
When does crossing over lead to genetic abnormalities?
Unequal crossover (chromatids misalign ---> chromosome with duplication and deletion)
91
What are the 3 results of unequal cross over?
1. Duplication
2. Deletion
3. Inversion
92
What is chromosome deletion?
Part of a chromosome is missing or deleted
93
What is chromosome duplication?
Portion of a chromosome is copied ---> extra genetic material
94
What is the most common result of unequal cross over?
Paracentric inversion
95
What is chromosome paracentric inversion?
Rearrangement of chromosomal segments in one same arm (doesn't include centromere)
96
What does paracentric inversion lead to? (2)
1. Usually unaffected carriers (may have reproductive problems)
2. Children with deletions/insertions
97
How can structural chromosomal abnormalities of carriers impact their offspring?
Partial trisomy or monosomy
98
How can paramentric inversion influence cancer?
t(9;22)(q34;q11) in Philadelphia chromosome
99
Are most structural chromosomal abnormalities inherited?
No - most de novo
100
How can chromosomal deletions be detected?
Microscope
- Microdeletion ---> v. high resolution banding
101
What are 2 examples of chromosomal deletion disorders?
1. Cri-du-chats syndrome - 46,del(5p)
2. Williams syndrome
102
What type of disorder is Cri-du-chat syndrome?
Chromosomal deletion
103
What is the karyotype of Cr-du-chat syndrome?
46,del(5p)
104
What is an example of a chromosomal microdeletion disorder?
DiGeorge syndrome
105
What type of disorder is DiGeorge syndrome?
Chromosomal microdeletion
106
What is the karyotype of DiGeorge syndrome?
22q11.2 del
107
What type of disorder is Williams syndrome?
Chromosomal deletion
108
What are the 5 symptoms of Williams syndrome?
1. Long philtrum
2. Short, upturned nose
3. Arched eyebrows
4. Supravalvular aortic stenosis
5. Cocktail party personality (no social anxiety)
109
What is Williams syndrome genetically?
7q11.23 deletion
110
How is Williams syndrome detected and why?
FISH (fluorescent in situ hybridisation) ---> detects lack of elastin
- Deletion too small
111
What are the 6 symptoms of 7q11.23 duplication syndrome?
1. Broad nose
2. Short philtrum
3. Flat eyebrows
4. Aortic dilation
5. Autistic behaviours
6. Delayed speech development
112
Do duplications or deletions of the same chromosome have a milder phenotype?
Duplications ---> less effect
113
What is Robertsonian translocation?
Translocation in acrocentric chromosomes resulting in a single chromosome with 2 q arms
114
What are the 3 classes of chromosomes?
1. Metacentric ---> p=q
2. Submetacentric ---> p
no p
115
Which class of chromosomes can undergo Robertsonian translocation?
Acrocentric
116
Which 5 chromosomes are acrocentric?
13, 14, 15, 21, 23
117
What are the 3 most common Robertsonian translocations?
1. 13 and 14 join
2. 14 and 15 join
3. 14 and 21 join (think multiple of 7)
118
What is usually the effect of Robertsonian translocations and why?
No effects
- No genetic material lost
119
What does chromosomal balance refer to?
Whether the genetic material in a chromosome in correct proportions
- Unbalanced ---> genetic abnormalities
120
What does 'rob' mean in chromosome nomenclature?
Robertsonian translocation
