Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

LS1 MGD > L16 - chromosome abnormalities > Flashcards

L16 - chromosome abnormalities Flashcards

1
Q

How many subunits do histones have?

A

8 - octamer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the structure of chromatin

A

Hanging loops of DNA on a protein scaffold

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

From which type of chromatin are genes expressed?

A

active chromatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which types of epigenetic modifications change chromatin from its inactive to active form?

A

DNA demethylation

Histone acetlyation etc…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which types of epigenetic modifications change chromatin from its active to inactive form?

A

DNA methylation

Histone deacetylation etc…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

In epigenetic modification changes are not made to which part of DNA structure?

A

The DNA sequence is not changed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Chromosomes from which part of the cell cycle are used for chromosome analysis?

A

Metaphase chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How are metaphase chromosomes gathered for chromosome analysis?

A

Living cell in vitro are cultured, chromosomes are gathered at metaphase by using spindle inhibitors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the name of the process whereby chromosomes are systematically sorted?

A

Karyotyping

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Different sample types of chromosomes yield chromosomes of different lengths. What different specimen types of chromosomes are used?

A 
Bone marrow
Blood (T-lymphocytes)
Amniotic fluid
CVS (chorionic villus sample)
Solid tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does karyotyping involve?

A

Metaphase chromosomes are:

  1. Stained
  2. Paired up and grouped together
  3. Described using standard nomenclature (ISCN 2013)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What type of chromosome contains no eukaryotic genes of consequence on its p arm?

A

acrocentric chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which type of chromosome has p and q arms of similar length?

A

metacentric chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Chromosomes are grouped from A to G by which properties?

A

Size and shape

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which chromosome was incorrectly number and is actually larger than its previous numbered chromosome?

A

chromosome 22 (is bigger than 21)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

G-banding is a staining method which uses trypsin to digest proteins which are then stained with Romanowski dye to produce light and dark bands. Why do the dark G (+ve) bands stain darker than the light G (-ve) bands?

A 
Dark G(+ve) bands are AT rich (gene poor)
Light G(-ve) bands are GC rich (gene rich)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How many pairs of chromosomes do humans have?

A

23 pairs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How many pairs of autosomes do humans have?

A

22 pairs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How many pairs of sex chromosomes do humans have?

A

1 pair

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe a normal male karyotype using the correct nomenclature

A

46,XY, Normal male karyotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are chromosome ideograms?

A

Standard diagrams which show the standard banding patterns for each chromosome.
Dark and light bands are numbered according to international convention: ISCN 2014 - therefore international results and research are comparable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is automated karyotyping?

A

Slides scanned automatically
Images taken
Digital karyotypes from images
Analyse chr’s paired up on screen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How are chromosomes described in a chromosome report?

A 
Using ISCN 2013 standard format:
1. Chromosome number
2. Sex complement
3. Structural changes
Separated by commas and NO SPACES!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Why do cytogenetic analysis?

A
  1. Accurate diagnosis/ prognosis of clinical poblems
  2. Better clinical management
  3. Assess future reproductive risks
  4. Prenatal diagnosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the types of constitutional abnormalities (abnormality present from birth) that cause people to be referred for cytogenetic analysis?

A
  1. Prenatal diagnosis
  2. Birth defects
  3. Abnormal sexual development
  4. Infertility
  5. Recurrent fetal loss
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the type of acquired abnormalities that cause people to be referred for cytogenetic analysis?

A
  1. Leukaemias
  2. Solid tumours
  3. Specific translocations/ abnormalities can give prognostic information (advise on best treatment)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is sampled in chorionic villus sampling?

A

Chorionic villus (placental tissue)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is sample in amniocentesis?

A

Amniotic fluid containing fetal tissues from the amniotic sac

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

When can CVS be done?

A

11-12 weeks gestation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

When can amniocentesis be done?

A

15 weeks onwards

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the risk of miscarriage with CVS?

A

1.2% miscarriage risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the risk of miscarriage with amniocentesis?

A

0.8% miscarriage risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What does trisomy 21 cause?

A

Down syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is meant be aneuploidy?

A

Loss and gain of whole chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Why does aneuploidy arise?

A

Due to errors at cell division of meiosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are the three viable trisomies at birth?

A

Down Syndrome
Patau syndrome
Edwards syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What trisomy causes Edwards syndrome?

A

Trisomy 18

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What trisomy causes Patau syndrome?

A

Trisomy 13

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Which is the only full monosomy syndrome to be viable?

A

Turner syndrome 45,X

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Why is Turner syndrome the only viable monosomy?

A

X chromosome inactivation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is polyploidy?

A

The gain of a whole haploid set of chromosomes e.g. 69,XXX

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is the most common form of polyploidy?

A

Polyspermy: fertilisation of an egg by more than one sperm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What type of polypoidy is accountable for 2-3% of all pregnancies and approximately 15% of all miscarriages (term deliveries die shortly after birth)?

A

triploidy

Diploid triploid mosaicism is seen in livebirths

44
Q

What can cause aneuploidy?

A
  1. Non-disjunction at one of the meiotic cell divisions

2. Can occur during cell division -> mosaicism

45
Q

What is meant by mosaicism?

A

Two cell populations present in an individual

46
Q

What is anaphase lag?

A

When chromosomes are “left-behind” at cell division. The lagging chromosomes may be lost entirely in mitosis or meiosis

47
Q

What are the causes of anaphase lag?

A

Defects in spindle function or attachment to chromosomes

48
Q

What is the incidence of Down syndrome?

A

1 in 650-1000

49
Q

What are individuals with Downs syndrome at higher risk of?

A

Leukaemia

Early alzheimers

50
Q

What are the signs and symptoms of Down Syndrome?

A

Hypotonia - decreased muscle tone
Characteristic facial features
Intellectual disability
Heart defects

51
Q

What is the incidence of Edwards syndrome?

A

1 in 6000

52
Q

What are the signs and symptoms of Edwards syndrome?

A 
Small lower jaw
Prominent occiput (back of head)
Low-set ears
Rocker bottom feet
Overlapping fingers
53
Q

Which sex is Edwards syndrome more common in?

A

Female predominance

54
Q

What causes Edwards syndrome?

A

Maternal meiosis II error

55
Q

What is the modal lifespan of a baby with Edwards syndrome?

A

5-15 days

56
Q

When is Edwards syndrome normally diagnosed?

A

Prenatally- presents with abnormal scan

57
Q

What are the signs and symptoms of Patau syndrome?

A

Multiple congenital abnormalities
Polydactyly
Holoprosencephaly (forebrain fails to split into 2 hemispheres) - present from single eye-> cleft lip

58
Q

What is the incidence of Patau syndrome?

A

1 in 12000

59
Q

What is the lifespan of a baby with Patau syndrome?

A

Majority die in neonatal period

60
Q

What are the signs and symptoms of Turner syndrome?

A 
Puffy feet
Redundant skin at back of neck (neck webbing)
Short stature
Heart defects
Mild learning difficulties
Infertility
61
Q

Which sex is Turner syndrome most common in?

A

45,X - therefore only occurs in females

62
Q

What causes phenotypic differences in the presentation of Turner syndrome?

A

The parental origin of X - majority of cases lack paternal X

63
Q

What is X chromosome inactivation?

A

Only one X chromosome is ever active in a human cell. This occurs because females have 2 and males have 1, therefore it ensures that they have the same chromosome complement

64
Q

Why is a single X chromosome a problem in Turner syndrome, since X chromosome inactivation occurs to make only a single chromosome active in a human cell anyway?

A

It affects pairing up of chromosomes at mitosis and meiosis. Although males have a single X chromosome the X and Y chromosomes have short regions in common called the pseudo-autosomal regions which can pair up.

65
Q

Which gene is present in the pseudoautosomal region that is associated with the short stature seen in Turner syndrome?

A

SHOX gene

66
Q

What is mosaicism?

A

Presence of 2 or more cell lines in an individual

67
Q

What causes mosaicism?

A

Usually caused by MITOTIC non-dysjunction

68
Q

Why is the degree of mosaicism in an individual so variable?

A

Degree of mosaicism depends on when the error occurred:

  1. First post zygotic division -> looks like a meiotic event
  2. Subsequent divisions -> 3 cell lines (monosomy cell line usually lost - unless X chromosome)
69
Q

What is the meaning of uniparental disomy (UPD)?

A

Presence of homologous chromosomes from one parent

70
Q

Why does UPD matter?

A

If the chromosomes is imprinted. Imprinted chromosomes show differential expression of specific genes depending on the parental origin of the chromosome,

71
Q

Why does UPD for the same chromosome cause two different disease: Prader-Willi and Angelman syndrome?

A

Imprinted genes show differential expression depending on the parental origin of the chromosome.
Prader-Willi syndrome is caused by paternally inherited chromosomes.
Angelman syndrome is caused by maternally inherited chromosomes.

72
Q

List the four “common” mechanisms to generate UPD

A
  1. Trisomy rescue
  2. Monosomy rescue
  3. Gamete complementation
  4. Mitotic error
    Each require two separate abnormal events
73
Q

Which is the most common mechanism to generate UPD?

A

Trisomy rescue

74
Q

What happens in trisomy rescue?

A

2 abnormal events:

  1. Meiotic error -> trisomy
  2. Mitotic error-> disomy (1 in 3 chance leads to UPD)
75
Q

How do you test for UPD?

A

Molecular genetic test using informative repetitive DNA markers on imprinted genes/ regions of interest, to see whether inheritance is bi-parental or not

76
Q

List the cytogenic structural abnormalities you can get

A 
Translocations - Robertsonian and Reciprocal
Inversions - paracentric and pericentric
Deletions - including microdeletions
Duplications
Insertions (into different chromosomes)
Rings
Marker chromosomes - small chromosome with centromere
Isochromosomes
77
Q

What is a reciprocal translocation?

A

A two-break rearrangement that is usually unique to a family. Carriers produce balanced and unbalanced gametes

78
Q

How do you assess umbalanced segregant outcomes?

A
  1. Establish likely segregation - viable offspring an option?
  2. Have the imbalances been reported before?
  3. Quote risks if established
79
Q

What is a Robertsonian translocation?

A

Two acrocentric chromosomes fused together

80
Q

In phenotypically normal, balanced carriers of Robertsonian translocations - how many chromosomes do you see?

A

45 - only time you see a normal individual with 45 chromosomes

81
Q

How does a Robertsonian translocation pair up during meiosis?

A

Forms a trivalent - not very stable

82
Q

What are Robertsonian carriers at risk of during meisosis?

A

Anueploidy

83
Q

Can homologous carriers of Robertsonian translocations have a normal pregnancy?

A

No - gametes always have a monosomy or trisomy

84
Q

What does der(14;21) mean?

A

A robertsonian translocation between chromosome 14 and 21.

85
Q

How do deletions arise?

A

Uneven pairing and recombination during meiosis

86
Q

What is the difference between a terminal and an interstitial deletion?

A

Terminal deletion - affects ends

Interstitial deletion - within arm

87
Q

What is the effect of deletions on the phenotype?

A

Likely (but not always) accounts for phenotype

88
Q

What is a microdeletion?

A

A deletion smaller than 100Kb

89
Q

How can you detect a microdeletion?

A

Can’t always see on G banding as its too small, need to use FISH technique to diagnose and confirm the specific region associated with the phenotype

90
Q

What is FISH?

A

fluorescent in situ hybridisation

91
Q

What is FISH used for?

A

To answer SPECIFIC questions. You need to know what you are looking for and therefore which probes to use for specific chromosomes or loci.

92
Q

How is FISH done?

A
  1. Denature chromosome and fluorescently labelled DNA probe to single strand
  2. Reanneal - hybridisation
  3. Wash to remove unbound probe
  4. Visualise using a fluorescent microscope
93
Q

What are locus/ gene specific FISH probes used for?

A

Microdeletion/ duplication syndromes that are too small to see on G banded chromosomes

94
Q

What are centromere probes used for?

A

Identifying chromosome of origin, marker chromosomes and copy number analysis

95
Q

What are whole chromosome paints used for?

A

To identify a chromosome in a rearrangement

96
Q

What are the benefits of using FISH probes for common aneuploidies (13,18,21,X and Y) compared to full karyotypes?

A

Full karyotypes take up to 14 days as cells need to be cultured, whereas FISH probes can be used on uncultured cells and take 24-48hrs. They also have 99+ % accordance with full karyotype.

97
Q

What different types of probes can be used in Leukaemia FISH and how do they work?

A
  1. Fusion probes - detect translocations of genes involved
  2. Breakapart probes - detect gene rearrangement
  3. Locus specific probes - detect amplifications e.g. oncogenes, her2, c-myc
98
Q

What are the benefits of microarray methodology?

A

Examines the whole genome at high resolution

99
Q

What can microarrays detect and not detect?

A

They can detect copy number changes but can’t detect balanced rearrangements or specific mutations which don’t results in a copy number change

100
Q

How are microarrays done?

A
  1. Take an equal amount of patient DNA and reference DNA - each with attached green or red fluorescent marker - and mix.
  2. Add to array slide spotted with oligonucleotides (60mers)
  3. Hybridise for 48 hours
  4. Wash slide
  5. Scan
  6. Input scan images to analysis software - detects ratio of green:red fluorescence and analyses relative copy numbers
101
Q

Who is referred for aCGH?

A
  1. Learning difficulties/developmental delay/multiple congenital abnormalites (15-20% abnormality rate)
  2. Normal karyotype
  3. Balanced de novo karyotype - is it really balanced?
  4. Unbalanced karyotypes to assess gene content
102
Q

What can array platforms detect?

A

copy number changes

loss of heterozygosity (using SNP)

103
Q

What are the advantages of aCGH?

A
  1. Examines the entire genome at high resolution
  2. Targeted against known genetic conditions and sub telomere regions
  3. 1 array is equivalent to many thousands of FISH investigations and can be automated
  4. Detailed information on genes in del/dup region
  5. Better phenotype/ genotype correlation
104
Q

What are the disadvantages of aCGH?

A
  1. Arrays are more expensive than karyotyping
  2. Will not detect balanced rearrangements - therefore not suitable for all referrals
  3. Copy number variation - genuine abnormality?
  4. Mosaicism may be missed
105
Q

What will be future developments for prenatal testing?

A
  1. Microarrays used instead of karyotyping for woman with an abnormal scan
  2. Non-invasive prenatal testing (NIPT) - free fetal DNA in maternal plasma tested, enough there to capture from 9 weeks gestation
  3. Digital PCR and next generation sequencing technology

LS1 MGD (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions