Chromosomes Flashcards
(115 cards)
1
Q
Describe two arms of chromosomes
A
Short, p arm
Long, q arm
2
Q
How are types of chromosomes classified? Give examples
A
Where centromere is:
Acrocentric: centromere at end
Metacentric: centromere in the middle
3
Q
What is at the tip of chromosomes?
A
Telomeres
4
Q
What do telomeres consist of?
A
TTAGGG tandem repeats (highly conserved)
5
Q
What purposes do telomeres serve?
A
Prevent chromosome shortening during replication
Differentiates chromosome ends from double strand breaks preventing end to end joining
6
Q
What replicates telomeres?
A
Telomerase
7
Q
How many homologous autosomes do humans have?
A
22
8
Q
What is meant by karyotype?
A
Number and appearance of chromosomes in nucleus of eukaryotic cell
9
Q
Describe method for G banding
A
1) Denature protein with trypsin
2) Stain with Giesma (DNA binding dye) -active/transcribed areas stain lightly due to less condensed chromatin
10
Q
What are chromosomes arranged on after G banding?
A
Karyogram
11
Q
What does FISH allow?
A
Used to identify a known mutation e.g. trisomy 21
12
Q
What is the resolution of karyotyping?
A
6-8mb of NDA
13
Q
What is the method for FISH?
A
Single stranded DNA (probe) to anneal to target sequence on metaphase spread
14
Q
When is chromosome painting used?
A
When you don’t know what you’re looking for (i.e. a generic translocation)
15
Q
Describe method for chromosome painting
A
Mixture of probes specific for each chromosome
These are colour labelled and anneal
16
Q
What is comparative genome hybridisation array used for
A
Detect regions of gene amplification/gene loss
Allow smaller bits of chromosomes to be identified (not normally seen on metaphase plate, higher resolution)
Can identify unusual chromosome patterns in cancers
17
Q
What is the method for Array CGH?
A
Test DNA labelled with red paint
Normal control DNA labelled with green paint
DNA hybridised
Gene amplification: DNA shows red
Gene loss: DNA shows green
18
Q
What chromosome identification method is used for dysmorphic individuals (unusual appearance)?
A
CGH used to detect chromosome abnormalities
Should check parents for abnormality to see if these gene abnormality is responsible for phenotype
19
Q
What is sex detrmining region of Y chromosome?
A
SRY gene
20
Q
What does presence of SRY on Y chromosome mean?
A
Maleness regardless of how many X chromosomes present
21
Q
How deos SRY lead to male differentiation (and how is female differentiation inhibited)?
A
Leads to testis production from Wolffian ducts. Testis sertoli cells make Mullerian inhibtory factor (inhibits female genitalia production)
22
Q
What is the genotype of Turner’s syndrome?
A
45X (XO)
23
Q
What are the symptoms of Turner’s syndrome?
A
Webbed neck, infertility, broad chest, no puberty, wide carrying angle
24
Q
What is the genotype for Klinefelter’s syndrome?
A
47XXY (XXY)
25
What are symptoms of Klinefelter's disease?
Breasts, infertile, slight ID and testis atrophy
26
What are effects of 47XXX genotype?
Female: Slight ID, tall
27
What is XYY genotype associated with?
Male: Aggression
28
Compare the amounts of products of X linked Gene products in males and females, why?
Same
Dosage compensation - inactivation of all but one X chromosome
29
What does the lyon hypothesis state about X inactivation in somatic cells of female?
Occurs in embryonic life
Is random (either X chromosome)
Permanent + complete
Clonally propagated through mitosis
30
Why is the Lyon hypothesis not always correct?
Inactivation not always random (structurally abnormal X preferentially inactivated)
Inactivation not complete
Inactivation not permanent (reversed in development of germ cells)
31
Where is inactivated X chromosome found?
Barr body
32
How many Barr bodies would 48 XXXX have, why?
3 Barr bodies
3 Inactive X chromosomes (one barr body for each inactive X)
33
How do Barr bodies appear histologically?
Dark nucleus-like structure on the cell periphery
34
What are structural chromosomal abnormalities (6)?
```
Translocation
Deletion
Insertion
Inversion
Ring
Isochromosome
```
35
What are examples of numerical abnormalities (2)?
Aneuploidy
| Polyploidy
36
What is the difference between aneuploidy and polyploidy?
Aneuploidy: Numerical change in cell's usual chromosomes (i.e. loss/gain of one chromosome)
Polyploidy: Numerical change in cell's usual chromosomal sets (i.e 3 chromosomes in every set)
37
How can trisomy caused by non disjunction in meiosis II?
Sister chromatids don't separate thus gamete contains 2 copies of one homologue
38
How can trisomy be caused by non disjunction in meiosis I?
Pair of homologous chromosomes fail to separate thus gamete contains both homologoues of one chromosome pair
39
What is the difference between a trisomy non-disjunction at meiosis I and II?
I - Contains both homologoues of one chromosome pair
II - Contains 2 copies of one homologue
40
What is mosaicism?
Presence in cell line of two or more cell lines with different genetic constitution but from same zygote.
41
What is the trisomy for Down Syndrome?
21
42
What can cause down syndrome?
Robertsonian translocation
Non-disjunction
43
What are symptoms of down syndrome?
Alzheimers, ID, cardiac problem widended sandal gap, leukaemias
44
What is a risk factor for trisomy (based on mother)?
Old maternal age
Spindle less likely to form
Non-disjunction
45
What is the trisomy in Patau syndrome?
13
46
What is the trisomy in Edward's Syndrome?
18
47
Symptoms of Pautau syndrome
Mental retardation
Clefting
Finger and toe abnormality
Cyclopia
48
Symptoms of Edward's syndrome
Rocker bottom feet, overlapping fingers, clenched fingers
49
What causes monosomy?
Non disjunction
Anaphase lag (loss of chromosome as it moves to pole of cell in anaphase)
50
What else does meiotic division produce to form monosomy cell?
Trisomic cell
51
What is polyploidy?
Addition of one or more complete haploid complements e.g. trisomy - 69 chromosomes
52
How does polyploidy arise?
Failure of maturation meiotic division in ovum/sperm gives diploid gamete
Fertilisation of ovum by 2 sperm
53
What is a translocation?
Transfer of genetic material from one chromosome to another
54
What are 2 types of translocation?
Balanced: no net gain/loss of material (generally harmless)
Unbalanced: incorrect amount of chromosome material (abnormalities arise)
55
What happens in a reciprocal translocation? Give an example
Break in 2 separate chromosomes, segments exchanged between 2 chromosomes to form 2 derivative chromosomes.
i.e Philadelphia chromosome from 9 and 22 in CML
56
What happens in a Roberstonian translocation?
Translocation where breakpoints are close to centromeres of 2 acrocentric chromosomes.
Followed by fusion of long arms
This results in the loss of short arms
Can occur between homologous or non-homologous chromosomes
57
What sort of chromosomes are affected by robertsonian translocation?
Acrocentric chromosomes
58
What are 2 types of robertsonian tranlocation?
Homologous acrocentrics or non homologous acrocentrics involved
59
What happens to short arms in robersonian translocation?
Lost, (no clinical effects)
60
What is the negative consequence of roberstonian translocation on gametes?
Can produce imbalanced chromosome complement
61
Describe a balanced roberstonian translocation
Long arms of chromosome 14 and 21 joined, along with normal 14 and normal 21 (i.e. equivalent to having separate copy of chromosome 21 and 14) therefore 2 copies of each and normal
62
Describe how a Robertsonian translocation can lead to trisomy 21
2 copies of 21
Long arms of 14 and 21 joined
1 other copy of 14
2 copies of 14 hence normal
But 3 copies of 21 hence Down syndrome
63
What is an isochromosome?
One arm of chromosome lost and other arm duplicates to replace it
Trisomy of duplicated arm and monosomy of lost arm
64
What is a ring chromosome?
Double deletion mutation (in both p and q arms) new ends join together to form ring , acentric fragments lost
65
What does ring chromosome 14 lead to?
Epilepsy, MR and craniofacial abnormality
66
What happens in an inversion?
2 breakages within chromosome and central segment reversed 180 degrees and reinsert into chromosome
67
What Is the difference between a paracentric and pericentric inversion?
Pericentric: involve p and q arm (more severe)
Paracentric: only involves one arm
68
What is an insertion (chromosome mutation)?
DNA inserted into chromosome e.g into regulatory element uncontrolled cell division.
69
What are different types of chromosome deletions? Examples?
Large deletion e.g. Wolf Hirschhorn
Microdeletion: DiGeorge, WAGR, williams syndrome
70
What normally causes mosaicism?
Non disjunction in early embryonic mitosis division
i.e. can have mosaic Down syndrome (some cells normal some cells have trisomy 21)
71
What is chimerism?
Present in individual of 2 or more genetically distinct cell lines derived from more than one zygote (i.e. different genetic origin)
72
What are causes of chimerism?
2 sperm, 2 eggs, one embryo
| Blood chimeras: (exchange of cells between non identical twins via placenta in utero)
73
What is a point mutation?
Substitution of a base
74
How does point mutations arise?
Spontaneous errors in DNA replication
Repair/error due to mutagens
75
What are 2 types of point mutation, what do they involve?
Transition: purine to purine or pyrimidine to pyrimidine
Transversion: purine to pyrimidine or vice versa
76
What is a synonymous mutation?
Doesn't change amino acid
77
What is a non-synonymous mutation?
Changes amino acid
78
What are two types of non synonymous mutation?
Missense (replace one AA with another)
Nonsense: codon specifying AA replaced by stop codon
79
What is an insertion/deletion mutation?
When other than 3 bases - frame shift (disrupt coding sequence)
Often produces premature stop codon
80
How can mutation (e.g. deletion, insertion, point mutation) in non coding region be bad?
Interfere with binding of TF to this region - reduce transcription of coding gene
81
What happens to trinucleotide repeats in replication?
Become unstable during replication can lead to amplification of more repeats (expansion)
Disease manifest when you pass certain threshold
82
How do trinucleotide repeat quantity change over generations , what's the effect?
Expansion progressive down generations (amplification in gametogenesis) so more severe phenotype with successive generations and more early onset diseases = anticipation
83
What is meant by anticipation?
Earlier onset + more severe phenotype going down generations
84
What types of cells does expansion occur in?
Somatic AND germ line cells
85
What causes expansion?
Strand slippage in DNA replication
86
What are the effects of amplification in non coding region?
Interfere with transcription, induce methylation and non functional promoter
87
Example of non coding region trinucleotide expansion
Fragile X syndrome
Myotonic dystrophy
88
What causes Fragile X syndrome?
Expansion of CGG
ID and large head/testes in boys, and female: premature ovarian follicle
89
What expansion causes myotonic dystrophy?
CTG repeat
90
What disease caused by amplification in coding regions?
Huntington's disease
91
What is ineritance pattern of Huntingdon's disease?
Autosomal dominant
92
What is the expansion in Huntingdon's disease?
CAG repeat
93
After how many repeats does Huntingdon's manifest?
>60 repeats: onset before 25
>35 repeats: positive predictive test
94
Describe penetrance of Huntingdon's disease?
100%
95
What are symptoms of Huntingdon's disease?
Progressive dementia, unsteady gait and jerky involuntary movement
96
What sort of point mutations can occur in non coding regions?
mRNA regulatorty elements (affect gene expression)
Mutation in splice sites (intron retention or exon skipping)
97
Most loss of function mutations are...
Recessive (cell can still function with 50% if gene product)
98
What is haploinsufficiency?
When 50% gene product not sufficient so abnormal phenotype
99
How can dominant negative effect arise from loss of function mutation?
Mutant protein lost function and interferes with protein of normal allele
100
Example of loss of function mutation?
Waardenburg syndrome
101
Most gain of function mutations are...
Dominant
102
Example of gain of function mutations
Huntington, Myotonic dystrophy and achondroplasia
103
What causes Prader Willi syndrome?
Failure of paternally inherited SNPRN gene
104
What can cause imprinted gene diseases?
Mutation, methylation abnormality, uniparental disomy (i.e. 2 copies of gene from dad no maternal one)
105
In down syndrome do all affected individuals have three separate copies of 21?
No
106
What may increase risk for down syndrome (2)?
Maternal age
Family carries a balanced translocation of chromosome 21
107
What is a non-transmissible disease, how can it occur?
Cannot be passed from one human to another. Somatic mutation
108
Does mitochondrial DNA encode all the mitochondrial respiratory chain?
No
109
Does mitochondrial DNA have a high mutation rate?
Yes
110
Is mitochondrial DNA present in multiple copies in each cell?
Yes
111
What is a chromosome abnormality incompatible with foetal life?
Autosomal monosomy
112
What is the smallest chromosome?
Male Y chromosome
113
Females are mosaics expressing either the maternal or paternal X-chromosome in different cells
True
114
Part of the Y-chromosome genome is homologous with part of the X-chromosome
True
115
Normal females inactivate the same X chromosome in the nucleus of all somatic cells.
False
