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Z OLD Molecules, Genes and Disease > Chromosome Abnormalities > Flashcards

Chromosome Abnormalities Flashcards

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Organic Chemistry 101 flashcards
1
Q

How is DNA packaged?

A

DNA wrapped around an octomer of histones

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2
Q

What does a octomer of histones consist of?

A

2 molecules each of H2A, H2B, H3 and H4

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3
Q

How many bp is in each octomer?

A

166

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4
Q

What is the purpose of histone H1?

A

It stabilises

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5
Q

How is higher order DNA structure established?

A

By hanging loops of DNA onto a protein scaffold to form chromatin

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6
Q

When are gene expressed?

A

When they form active chromatin

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7
Q

How can chromatin switch between active and inactive?

A

Epigenetic modification

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8
Q

How is chromatin converted from active to inactive?

A

By DNA methylation and histone deacetylation

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9
Q

How is chromatin converted form inactive to active?

A

DNA demethylation, histone acetylation

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10
Q

Where are changes made in activation and inactivation of chromatin?

A

To DNA and histones, not actual DNA sequence

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11
Q

What is being studies in chromosome analysis?

A

Metaphase chromosones

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12
Q

What does the study of metaphase chromosomes require?

A

Living cells for in vitro growth

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13
Q

What must be done to study metaphase chromosomes?

A

The cells must be cultured, accumulated at metaphase and harvested

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14
Q

Why does analysis of metaphase chromosomes take a long time?

A

Because it must be done stepwise

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15
Q

What are the steps in the analysis of metaphase chromosomes?

A
  • Add spindle inhibitor
  • Make hypotonic
  • Add fixative
  • Slides prepared and stained
  • Visualised on light microscope
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16
Q

Give an example of a spindle inhibitor

A

Colcemid

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17
Q

What can be added to make the cell culture hypotonic?

A

Potassium chloride in varying concentrations

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18
Q

What fixative can be used in metaphase chromosome analysis?

A

3:1 methanol:acetic acid

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19
Q

What can the slides in metaphase chromosome analysis be stained with?

A

Giemsa stain

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20
Q

How are the slides from metaphase chromosome analysis interpreted?

A

Count, go through systematically to check all pairs, and check banding pattern is the same for each pair

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21
Q

What specimen types can be used for chromosome analysis?

A
  • Bone marrow
  • Blood (T-lymphocytes)
  • Amniotic fluid
  • CVS
  • Solid tissue
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22
Q

How are bone marrow and blood for chromosome analysis grown?

A

In suspension

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23
Q

How long is bone marrow cultured for?

A

0-1 day

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24
Q

What long is blood cultured for?

A

2-3 days

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25
Q

Where is amniotic fluid, CVS and solid tissue grown for use in chromosome analysis?

A

On substrate

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26
Q

How long is amniotic fluid, CVS and solid tissue cultured for?

A

7-21 days

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27
Q

What do different sample types yield?

A

Chromsomes of differing lengths

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28
Q

How does the process of chromosome analysis differ depending on the sample type?

A

It doesn’t

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29
Q

What is true of chromosome analysis of all sample types?

A

Defined quality scores required to meet

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30
Q

How can chromosomes be analyses?

A

Karyotyping

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31
Q

What is karyotyping?

A

Systematic sorting of chromosomes

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32
Q

How is karyotyping carried out?

A

Metaphase chromosomes stained, paired up and grouped together

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33
Q

How are chromosome abnormalities described?

A

Using standard nomenclature ISCN

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34
Q

What are chromosomes composed of?

A

2 arms

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35
Q

What are the 2 arms of the chromosome called?

A

NAME?

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36
Q

What are the possible configurations of the chromosome arms?

A
  • Metacentric- centromere in the centre, so p and q arms same length
  • Submetacentric- centromere slightly more to one side, so p arm shorter than q arm
  • Acrocentric- the centromere is the right at the end, so only the q arm is present
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37
Q

What does the p arm not contain in acrocentric chromosomes?

A

Euchromatic material, and therefore no genes of importance

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38
Q

What are chromosomes grouped based on?

A

Size and shape

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39
Q

What are the groups of chromosomes?

A

A → G

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40
Q

What groups are acocentric chromosomes?

A

D and G

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41
Q

What do groups D and G have on their p arms?

A

Satellites

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42
Q

Which of the chromosomes are not in size order?

A

22 is bigger than 21

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43
Q

What group is the X chromosome considered to be in?

A

C

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44
Q

What group is the Y chromosome considered to be in?

A

G

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45
Q

What methods of staining chromosomes are there?

A
  • Solid staining
  • G-banding
  • C-banding
  • Q-banding
  • Replication
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46
Q

How is G-banding carried out?

A

NAME?

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47
Q

What is produced from G-banding?

A

Dark and light bands

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48
Q

Why are the metaphases exposed to trypsin?

A

It digests proteins differentially

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49
Q

Give 2 examples of Romanawksi type dyes?

A

NAME?

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50
Q

Which of the bands are gene rich in G banding?

A

The light G-ve bands

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51
Q

What are the dark G+ve bands in gene banding rich in?

A

AT

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52
Q

What are the light G-ve bands in gene banding rich in?

A

GC

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53
Q

What is shown in chromosome ideograms?

A

Standard banding pattern for each chromosome

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54
Q

How are the dark and light bands produced in chromosome ideograms numbered?

A

According to international convention ISCN

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55
Q

What does C-banding do?

A

Stains heterochromatin at centromeres, and 1, 9, 16 and Y q

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56
Q

When would the C-banding staining method be used?

A

If wanted to determine if change in chromosome is abnormality, or normal variations

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57
Q

What happens to normal chromosomes?

A

The chromosome lengths vary

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58
Q

What does Q-banding determine?

A

Y q variation

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59
Q

When would the replication staining method be used?

A

When testing for an active or inactive X in females

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60
Q

How can karyotyping be carried out faster?

A

Using automated or semi-automated systems

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61
Q

What happens in automated karyotyping?

A

The slides are scanned, images are taken, and digital karyotyping from images is carried out by cutting out the chromosomes and pairing them up on screen

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62
Q

What is the advantage of comparing chromosomes paired up on the screen?

A

Easier to compare chromosomes when lined up side by side

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63
Q

What is the problem with automated karyotyping?

A

It’s expensive and time consuming to create equipment

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64
Q

What is used to describe the karyotype in a chromosome report?

A

Standard ISCN format

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65
Q

How are chromosomes described using the standard ISCN format?

A

Chromosome number, sex complement and structural changes are given, separated by a comma

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66
Q

What is a chromosome report for a normal female?

A

46,XX

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67
Q

What is the chromosome report for a normal male?

A

46,XY

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68
Q

What is the chromosome report for a female with an extra chromosome 21?

A

47,XY,+21

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69
Q

What is the chromosome report for a male with a chromosome 7 inversion?

A

46,XY,inv(7)(p.11.2q11.3)

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70
Q

What happens in an inversion?

A

Segment between two break points is inverted

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71
Q

When are spaces found in the karyotype?

A

Never

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72
Q

What is the purpose of cytogenic analysis?

A
  • Accurate diagnosis/prognosis of clinical problems
  • Better clinical management
  • Assess future reproductive risk
  • Prenatal diagnosis
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73
Q

How can cytogenic analysis be involved in the accurate diagnosis/prognosis of clinical problems?

A
  • Can identify the syndrome associated with an abnormality
  • Accounts for the phenotype
  • Accounts for pregnancy loss
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74
Q

Give an example of where cytogenic analysis can lead to better clinical management?

A

In the case of Klinefelter syndrome, where if detected before puberty, the person can lead a relatively normal life

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75
Q

What is Klinefelter syndrome?

A

When people carry 2 X chromosomes, as well as Y chromosome

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76
Q

When is the assessment of future of reproductive risk important?

A

When people already have an affected child

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77
Q

What future reproductive risk can be assessed using cytogenic analysis?

A

The risk of a live born abnormal child

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78
Q

What happens to the risk of having a Downs syndrome child after a previous Downs pregnancy?

A

It increases by 1%

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79
Q

Why is prenatal diagnosis important?

A

It provides information to clinicians and parents, who can then choose to terminate, or clinicians can plan for when the child is born

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80
Q

Why may a pregnant woman be referred?

A
  • If the foetus displays constitutional abnormalities
  • Infertility
  • Recurrent fetal loss
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81
Q

What are constitutional abnormalities?

A

Abnormalities present from birth

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82
Q

Give 2 constitutional abnormalities

A
  • Birth defects

- Abnormal sexual development

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83
Q

What acquired abnormalities may be reason for referral for cytogenic analysis?

A
  • Leukaemia’s

- Solid tumours

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84
Q

What kind of leukaemia’s are there?

A
  • Acute
  • Chronic
  • Myelodysplasia/myeloprolifierative disorders
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85
Q

What can specific translocation/abnormalities found in cancers give?

A

Prognostic information

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86
Q

How is Down syndrome screened for?

A

Maternal serum screening

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87
Q

How is maternal serum used to determine risk of Down syndrome?

A

Biochemical markers found in serum, as well as gestation and age are inserted into an algorithm, which can be used to determine chance

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88
Q

What happens if the chance of Down syndrome is found to be higher than 1 in 150 in a screening test?

A

An invasive test is offered

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89
Q

When is routine screening of foetuses performed?

A

First trimester

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90
Q

What happens in first trimester screening?

A

Test for biochemical markers and nuchal translucency on an ultrasound scan

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91
Q

What is happening as foetal scanning improves?

A

More abnormalities are found using ultrasound

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92
Q

Give 4 disorders that can be picked up on an abnormal ultrasound scan

A
  • Cystic hygroma
  • Cleft lip/plate
  • Heart abnormality
  • Limb abnormalities
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93
Q

What is a cystic hygroma?

A

A swelling at the back of the neck

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94
Q

What can be detected on prenatal DNA studies?

A

NAME?

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95
Q

What chromosome abnormalities can be detected prenatally?

A

FH chromosome abnormaility

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96
Q

How are DNA studies carried out prenatally?

A

DNA is directly extracted from chorionic villus

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97
Q

Give 5 examples of birth defects

A
  • Dysmorphism
  • Congenital malformations
  • Mental retardation
  • Developmental delay
  • Specific syndromes
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98
Q

What can result from developmental delay?

A

NAME?

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99
Q

Give 3 specific syndromes that are birth defects

A
  • Downs syndrome
  • Williams syndrome
  • DiGeorge syndrome
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100
Q

What is aneuploidy?

A

The loss or gain of whole chromosomes

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101
Q

What does aneuploidy result from?

A

Due to errors at cell division in meiosis

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102
Q

What are the two main types of aneuploidys?

A
  • Trisomies

- Monosomies

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103
Q

Give 3 examples of trisomies

A
  • Down syndrome
  • Patau syndrome
  • Edwards syndrome
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104
Q

What is the only viable monosomy?

A

Turners syndrome

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105
Q

What happens in Turners syndrome?

A

X-inactivation

106
Q

What is polyploidy?

A

Gain of a whole haploid set of chromosomes

107
Q

What is the most common of polyploidy?

A

Polyspermy

108
Q

What is polyspermy?

A

The fertilisation of an egg by more than one sperm

109
Q

How many pregnancies does triplody occur in?

A

2-3% of pregnancies

110
Q

What % of miscarriages are caused by triploidy?

A

~15%

111
Q

What happens to triploidy deliveries?

A

They die shortly after birt h

112
Q

How many pregnancies does tetraploidy occur in?

A

1-2%

113
Q

Where are tetraploid cells often found?

A

At prenatal diagnosis

114
Q

What is the tetraploidy finding at prenatal diagnosis often caused by?

A

A cultural artefact caused by the failure of cell membranes to divide

115
Q

What is seen in live births where babies die shortly after?

A

Diploid/triploid mosaicism

116
Q

What does aneuploidy originate from?

A

Non-disjunction at one of the meiotic cell divisions

117
Q

What does non-disjunction at one of the meiotic cell divisions form?

A

Gametes with a missing chromosome, and an extra chromosome

118
Q

What affects the viability of gametes with missing or added chromosomes?

A

Which chromosome is involved

119
Q

When can non-disjunction occur, other than in meiosis?

A

During mitotic cell division

120
Q

What is the result of non-disjunction in mitotic cell division?

A

Mosaicism

121
Q

What is mosaicism?

A

Two cell populations within an individual

122
Q

What is meiosis?

A

The method by which we go to 46 diploid to 23 haploid

123
Q

How can non-disjunction in meiosis occur?

A

NAME?

124
Q

What normally happens when both chromosomes go into one cell in the first meiotic division?

A

Non-viable cell will be lost

125
Q

What is the result when the cell is not lost when both chromosomes go into one cell in the first meiotic division?

A

2 gametes with 2 chromatids, and 2 with none

126
Q

What is the result of both chromatids going into one cell at the second meiotic division?

A

Leaves one gamete with 2 chromatids, and one game with no chromatids

127
Q

What can fertilisation of a gamete that has no or two chromatids with a normal gamete lead to?

A

Trisomy or monosomy

128
Q

When may a pregnancy be viable despite the gametes being produced from meiosis where non-disjunction has occurred?

A

When the chromosome is 13, 18 or 21- the X must be involved

129
Q

What happens in anaphase lag?

A

Chromosomes can be ‘left behind’ at cell division

130
Q

What may cause anaphase lag?

A

Because of defects in spindle function or attachment to chromosomes

131
Q

What can result from anaphase lag?

A

The lagging chromosome may be lost entirely in mitosis or meiosis

132
Q

What is trisomy 21?

A

Down syndrome

133
Q

What is the frequency of Downs syndrome?

A

1 in 650-1000

134
Q

What is Down syndrome characterised by?

A
  • Hypotonia
  • Characteristic facial features
  • Intellectual disability
  • Heart defects
  • Increased prevalence of leukaemia
  • Increased prevalence of early Alzheimers
135
Q

What is trisomy 18?

A

Edwards syndrome

136
Q

What is the incidence of Edwards syndrome?

A

1 in 6000, with female predominance

137
Q

What causes Edwards Syndrome?

A

Maternal meiosis 11 error

138
Q

What is the medial lifespan of a Edwards Syndrome sufferer?

A

5-15 days

139
Q

How are nearly all diagnoses of Edwards Syndrome made?

A

Prenatally

140
Q

What are the symptoms of Edwards Syndrome?

A
  • Small lower jaw
  • Prominent occiput
  • Low-set ears
  • Rocker bottom ears
  • Overlapping fingers
141
Q

What is trisomy 13?

A

Patau syndrome

142
Q

What is Patau syndrome?

A

Multiple congenital abnormalities, including polydactyl, and holoprosencephaly

143
Q

What is the incidence of Patau Syndrome?

A

1 in 12,000

144
Q

What is the chance of survival with Patau syndrome?

A

Majority die in neonatal period

145
Q

What causes the majority of cases of Turner syndrome?

A

Absent paternal X

146
Q

What do phenotypic differences in Turners syndrome depend on?

A

The parental origin of X

147
Q

What are the symptoms of Turners syndrome?

A
  • Short-stature
  • Heart defects
  • Mild learning defects
  • Neck webbing
  • Puffy feet
  • Infertility
148
Q

What is active in human cells?

A

Only one chromosome

149
Q

What is the purpose of X inactivation?

A

Ensures that individuals have the same X chromosome complement that is active, as females have 2 X chromosomes, whereas males only have 1

150
Q

What do X and Y chromosomes have in common?

A

Short regions at the tips of the long and short arms

151
Q

What is at the short regions at the end of the P and Q arms of X and Y chromosomes?

A

Two pseudo-autosomal regions (PAR1 and PAR2)

152
Q

What do PAR1 and PAR2 do?

A

Essential for pairing during mitosis

153
Q

What will Turners syndrome patients be regarding the PARs?

A

They will be monosomic for the genes

154
Q

What gene is found within PAR?

A

SHOX

155
Q

What is the SHOX gene associated with?

A

Short stature

156
Q

What is mosaicism?

A

Presence of 2 or more cell lines in an individual

157
Q

What usually causes mosaicism?

A

Mitotic non-disjunction

158
Q

Where is mosaicism found?

A

Either throughout the body, or tissue limited

159
Q

What does the degree of mosaicism depend on?

A

When the error occured

160
Q

What happens if the mitotic disjunction occurs in the first post zygotic division?

A

There is no mosaicism, and the disjunction looks like a meiotic event

161
Q

How can mitotic non-disjunction lead to a non-mosaic karyotype?

A

In the first post-zygotic division, one cell gets 47,+N, and one gets 45,-N. The monosomy cell line is usually lost unless it involved X, as it is not viable, and the 47,+N then divides to produce 2 47,+21 gametes

162
Q

What happens if the mitotic disjunction occurs in subsequent divisions?

A

There are 3 cell lines, of which the monosomy cell line is usually lost
The first 46,N cell divides into 2 46,N cells. If there is non-disjunction in one of those cell lines, the gametes are 27+N and 45,-N. The monosomy cell line is usually lost unless it involves the X chromosome

163
Q

What is uniparental disomy (UPD)?

A

Presence of homologous chromosomes from one parent

164
Q

What is isodisomy?

A

2 identical chromosomes from one parent

165
Q

What is heterodisomy?

A

2 homolougous chromosomes from one parent

166
Q

What is segmental UPD?

A

When only one part of the chromosome is involved

167
Q

What is acquired UDP?

A

Solid tumours and leukemias

168
Q

What do imprinted chromosomes show?

A

Differential expression of specific genes, depending on the parental origin of the chromosome

169
Q

What is the effect of UDP is the chromosome involved is not imprinted?

A

It has no phenotypic efect

170
Q

What chromosomes can UDP syndromes occur in?

A

6, 7, 11, 14, 15 and 16

171
Q

Give 3 examples of UDP syndromes

A
  • Prader-Willi (15)
  • Russel-Silver (7)
  • Beckwith-Wiedeman (11)
172
Q

What are the 4 ‘common’ mechanisms to generate UDP?

A
  • Trisomy rescue
  • Monosomy rescue
  • Gamete complementation
  • Mitotic error
173
Q

What do each UDP generation mechanisms require?

A

Two separate abnormal events

174
Q

What is the most common mechanism of generating UDP?

A

Trisomy rescue

175
Q

What happens in trisomy rescue?

A

If a disomic gamete from a meiotic error combines with a monosomic gamete, will get a trisomic conceptus. If then, during post-zygotic mitosis, a mitotic error occurs, there is a 1 in 3 chance of loosing the single chromosome from the monosomic gamete, leaving the 2 from the same gamete

176
Q

What does trisomy rescue usually produce?

A

Heterodisomy

177
Q

How can UDP be tested for?

A

Using molecular genetic testing, using information from repetitive DNA markers on imprinted genes/regions of interest

178
Q

What does molecular genetic testing for UDP show?

A

Wether inheritance is bi-parental or not

179
Q

What can be determined if a UDP test is confirmed?

A

It identifies the parental origin and allows the syndrome to be defined

180
Q

What are the possible cytogenetic structural abnormalities?

A
  • Translocations
  • Inversions
  • Deletions
  • Duplications
  • Insertions
  • Rings
  • Marker chromosomes
  • Isochromosomes
181
Q

What are the two types of translocations?

A
  • Reciprocal

- Robertsonian

182
Q

What are the two types of inversions?

A
  • Paracentric

- Pericentric

183
Q

What does the type of inversion that occurs depend on?

A

Wether the break point is within the same chromosome arm, or in both chromosome arms

184
Q

What is generally true of marker chromosomes?

A

Generally quite small, and have a centromere that are not easily identifiable from banding pattern

185
Q

What are isochromosomes?

A

Ones that are identical at both ends- mirror images

186
Q

What are reciprocal translocations?

A

Two break rearrangements- there is a break in one chromosome, and a break in another, giving two segments of a chromosome that basically swap over

187
Q

What are reciprocal translocation usually unique to?

A

A family

188
Q

What is the exception to reciprocal translations being unique to families?

A

t(11;22)

189
Q

What do carriers of reciprocal translations produce?

A

Balances and unbalanced gametes

190
Q

What tends to happen if an individual carries a reciprocal translocation?

A

They are phenotypically normal

191
Q

Why are reciprocal translocation carriers phenotypically normal?

A

All the chromosomal material is there, just in a different place

192
Q

What is wether unbalanced offspring have abnormal phenotypes dependent?

A

Which regions are in trisomy, and which in monosomy

193
Q

How can translocation imbalance be assessed?

A

Segregation analysis using a pachytene diagram

194
Q

What are the 3 segregation types in reciprocal translocations?

A
  • Alternate
  • Adjacent 1- non homologous centromeres
  • Adjacent 2- homologous centromere
195
Q

What is the most common form of segregation that gives imbalance?

A

Adjacent 1- non homologous centromeres

196
Q

What can be produced from adjacent 2?

A

3:1 disjunction and 4:0 disjunction, both of which are unbalanced

197
Q

What does translocation form?

A

Quadrivalent

198
Q

What is produced when segregation is alternate?

A

Either two normal chromosomes, or two derivative chromosomes

199
Q

What needs to be done to assess unbalanced segregant outcomes?

A
  • Establish likely segregation
  • Check to see if imbalances have been reported before
  • Quote risks if established
200
Q

What causes Robertsonian translocations?

A

Two acrocentric chromosomes fusing together

201
Q

Which are the acrocentric chromosomes?

A

13, 14, 15, 21 and 22

202
Q

What kind of Robertsonian translocations can be produced?

A

Mono or dicentric

203
Q

What is the most common Robertsonian translocation?

A

13;14

204
Q

What is the chromosome count in balanced carriers of Robertsonian translocations?

A

45

205
Q

Why is the chromosome count 45 in balanced carriers of Robertsonian translocations?

A

Because two chromosomes are fused together

206
Q

What is formed at meiosis in Robertsonian translocations?

A

Trivalent

207
Q

Are trivalents stable?

A

No

208
Q

What is the risk with Robertsonian translocations?

A

Aneuploidy risk

209
Q

Who is at higher risk from Robertsonian translocations?

A

Females

210
Q

What are homologous carriers of Robertsonian translocations unable to do?

A

Have normal pregnancies

211
Q

Why can homologous carriers of Robertsonian translocations have normal pregnancies?

A

Because they can only pass over the Robertsonian chromosome

212
Q

What do deletions arise through?

A

Uneven pairing and recombination during meiosis

213
Q

What are the two types of deletions in chromosomes?

A

NAME?

214
Q

Where does a terminal deletion affect?

A

The ends of the chromosome

215
Q

Where does an interstitial deletion affect?

A

Within the arms of the chromosome

216
Q

What is required to diagnose or confirm a microdeletion?

A

FISH technique

217
Q

Why is the FISH technique required to diagnose or confirm microdeletions?

A

Because they can’t always be seen on G bandings, because the resolution of a G banded karyotype is around 5-10M (depending on what sample type you’re looking at), and some microdeletions are only around 100Kb in size

218
Q

What must be done when reporting abnormal results of chromosome analyses?

A
  • Give correct ISCN
  • Describe abnormality in words and what it means
  • Balanced or unbalanced
  • Is there monosomy/trisomy for a region
  • Relate to clinical problems
  • Request parental/family samples if required
  • Refer to clinical genetics
  • Provide appropriate literature if available
219
Q

What kind of technique is FISH?

A

Molecular cytogenetic

220
Q

What does FISH allow?

A

The answering of specific questions

221
Q

What is a requirement for FISH?

A

Need to know what we’re looking for

222
Q

What is used in FISH?

A

Probes for specific chromosome or loci

223
Q

How is FISH carried out?

A
  • A DNA probe is flourescently labelled
  • Target material is added to DNA probes, and heat to denature probe and chromosomes to single strand
  • Hybridisation by reannealing at 37º c .
  • Washing to remove unbound probe
  • Visualisation under fluorescence microscope
224
Q

What are the 4 types of probes used in FISH?

A
  • Locus/gene specific probes
  • Centromere probes
  • Telomere probes
  • Whole chromosome paints
225
Q

What are locus/gene specific probes used for?

A

Detecting microdeletion/duplications syndromes that are too small to see on G-banded chromosomes

226
Q

What size are centromere probes?

A

Large

227
Q

What is the advantage of centromere probes being large?

A

Easy to see

228
Q

What are centromere probes used for?

A
  • To identify the chromosome of origin
  • Visualise metaphase and interphase
  • Copy number analysis
  • Identifying derivative chromosomes and markers
229
Q

What are whole chromosome paints used for?

A

To identify a chromosome in rearrangement

230
Q

What is prenatal aneuploidy screening (PND) analysing?

A

Interphase

231
Q

What can be used for PND?

A

Cultured cells or uncultured cells

232
Q

How long are cells cultured in PND?

A

Up to 14 days

233
Q

What does PND culturing cause?

A

Anxiety

234
Q

What is used in uncultured cells in prenatal aneuploidy screening?

A

FISH probes for 13, 18, 21, X and Y

235
Q

What areFISH probes for 13, 18, 21, X and Y used in prenatal aneuploidy screening?

A

Because these are common aneuploidies

236
Q

How quickly can a result for prenatal aneuploidy screening be obtained?

A
  • For those testing using FISH probes, 24-48 hours

- A full karyotype in 14 days

237
Q

What is the concordance rate of prenatal aneuploidy screening using the FISH probes compared with the full karyotype?

A

99+%

238
Q

What does microarray examine?

A

The whole genome at high resolution

239
Q

What can be looked for using microarray?

A

Copy number changes

240
Q

What can’t be detected using microarray?

A

Balanced rearrangements or mutation

241
Q

What does microarray compare?

A

Patient DNA to normal control DNA

242
Q

What are the advantages of microarray technology?

A

High resolution
Lots of different genetic conditions can be looked at at once
Automated
Get detailed information about the genes

243
Q

What are the disadvantages of microarray?

A

Cost compared to karyotype
Will not detect balanced rearrangements , copy number variation and what is abnormal
Mosaicism may be missed

244
Q

What can cause problems with microarray technology?

A

Variation of uncertain significance

245
Q

Why does variation of uncertain significance create a problem?

A

Because there could be a novel pathogenic call (not seen before), a novel call with no genes in that region or a novel call that doesn’t fit with the patient phenotype

246
Q

What does non-invasive prenatal resting use?

A

Cell free foetal DNA found in the maternal plasma from 9 weeks gestation

247
Q

What is the problem with non-invasive prenatal testing?

A

Technically challenging

DNA quality deteriorates quickly

248
Q

How is the problem of the quality of DNA deteriorating quickly in prenatal genetic testing overcome?

A

Using special tubes to stabilise sample

249
Q

What techniques are used for non-invasive prenatal testing?

A

Digital PCR

Next generation sequencing

250
Q

What does NIPT reduce?

A

The need for invasive testing

251
Q

What may invasive testing be needed?

A

Confirmation of abnormal NIPT

252
Q

What aspect of NIPT has been approved?

A

NIPT testing for single gene disorders

253
Q

What does next generation sequencing allow?

A

Fragmenting of genomic DNA

254
Q

What is the advantage of fragmenting of genomic DNA?

A

So it can all be sequenced at the same time

255
Q

What does next generation sequencing create?

A

A lot of data which needs to be protected and stored carefully

256
Q

What is next generation sequencing suitable for?

A

Multiplexing with biological barcodes

257
Q

What is used to conform NGS findings?

A

Sanger sequencing

258
Q

What is the advantage of NGS sequencing?

A

It reduces the cost of testing individual genes by offering panels of gene testing

259
Q

What is whole exome sequencing?

A

The targeted sequencing of al exons

260
Q

What must be done in whole exome sequencing?

A

Identify de novo mutations in trio analysis

Z OLD Molecules, Genes and Disease (14 decks)

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