S14) Chromosomal Mutations Flashcards

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1
Q

What is cytogenetics?

A

Cytogenetics is the study of the genetic constitution of cells through the visualisation and analysis of chromosomes

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2
Q

What are the benefits of cytogenetic analysis?

A
  • Accurate diagnosis/prognosis of clinical problems
  • Better clinical management e.g. hormone treatment for Klinefelter syndrome
  • Prenatal diagnosis
  • Assess future reproductive risks
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3
Q

In terms of constitutional abnormalities, identify some referral reasons for cytogenetic analysis

A
  • Prenatal diagnosis
  • Birth defects
  • Abnormal sexual development
  • Infertility
  • Recurrent foetal loss
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4
Q

In terms of acquired abnormalities, identify some referral reasons for cytogenetic analysis

A
  • Leukaemia’s (acute/chronic diseases)
  • Solid tumours
  • Specific translocations/abnormalities
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5
Q

Identify and describe two prenatal diagnostic methods

A
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6
Q

Identify 4 birth defects

A
  • Dysmorphism
  • Congenital malformations
  • Mental retardation
  • Developmental delay
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7
Q

Which three biochemical techniques are used in cytogenic analysis?

A
  • Karyotyping
  • Fluorescent in situ hybridisation (FISH)
  • Microarray comparative genomic hybridisation (aCGH)
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8
Q

Briefly describe the process of karyotyping (chromosome analysis)

A

Karyotyping is the systematic sorting of chromosomes:

⇒ Whole genome screen

⇒ Metaphase chromosomes stained, paired up, grouped together

⇒ Abnormalities described using standard nomenclature

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9
Q

Outline the steps involved in chromosome analysis

A

⇒ Count the number of chromosomes

⇒ Identify each chromosome pair

⇒ Assess any missing/extra material

Recheck all chromosomes independently

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10
Q

Provide examples of standard nomeclature for the following:

  • Normal female
  • Normale male
  • Female with trisomy 21
  • Male with chromosome 7 inversion
A
  • Normal female – 46,XX
  • Normal male – 46,XY
  • Female with trisomy 21 – 47,XX,+21
  • Male with chromosome 7 inversion – 46,XY,inv(7)(p11.2q11.23)
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11
Q

Aneuploidy is a numerical cytogenetic abnormality.

Define it

A

Aneuploidy is the loss/ gain of whole chromosomes and arise due to errors at cell division in meiosis

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12
Q

Identify some examples of aneuploidy where whole chromosomes are lost and identify their associated diseases

A
  • Trisomies – Down syndrome +21, Patau syndrome +13 and Edwards syndrome +18
  • Monosomies – Turner syndrome 45,X (X inactivation)
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13
Q

What is polyploidy?

A

Polyploidy is the gain of a whole haploid set of chromosomes (an example of aneuploidy) eg. triploid 3n – 69, XXX

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14
Q

What are the causes of polyploidy?

A

The most common cause of polyploidy is polyspermy i.e. fertilisation of an egg by more than one sperm

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15
Q

Aneuploidy is due to non-disjunction during cell division.

Describe how this occurs

A
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16
Q

What is anaphase lag?

A
  • Anaphase lag is when chromosomes are ‘left behind’ at cell division because of defects in spindle function or attachment to chromosomes
  • The lagging chromosomes may be lost entirely in mitosis or meiosis
17
Q

What is Down syndrome?

A
  • Down Syndrome is a genetic condition arising due to trisomy 21 (third copy of chromosome 21)
  • It manifests with characteristic facial features, intellectual disability, heart defects and increased prevalence of leukaemia
18
Q

What is Edwards syndrome?

A
  • Edwards syndrome is a genetic condition arising due to trisomy 18 (third copy of chromosome 18) in maternal meiosis II
  • Babies survive for 5-15 days and it manifests with a small lower jaw, prominent occiput, low-set ears, rocker bottom feet and overlapping fingers
19
Q

What is Patau syndrome?

A
  • Patau syndrome is a genetic condition arising due to trisomy 13 (third copy of chromosome 13)
  • Majority die in neonatal period and it manifests with holoprosencephaly, polydactyly and multiple other congenital abnormalities
20
Q

What is Turner’s Syndrome?

A
  • Turner syndrome is a genetic condition occurring when one normal X chromosome is present in a female’s cells and the other sex chromosome is missing / structurally altered (X inactivation)
  • It presents with puffy feet, short stature, heart defects, mild learning difficulties, neck webbing, infertility
21
Q

What is mosaicism?

A
  • Mosaicism is the presence of 2/more cell lines in an individual, usually caused by mitotic non-disjunction
  • Occurs throughout the body or tissue limited & degree of mosaicism depends on when the error occurred
22
Q

Identify 5 cytogenetic structural abnormalities

A
  • Translocations
  • Inversions
  • Deletions
  • Duplications
  • Insertions
23
Q

What are recipocial translocations?

A
  • Reciprocal translocations are usually an exchange of material between nonhomologous chromosomes wherein carriers produce balanced and unbalanced gametes
  • If unbalanced offspring will have an abnormal phenotype dependant on regions of trisomy and monosomy
24
Q

What are robertsonian translocations?

A

- Robertsonian translocations are a rare form of chromosomal rearrangement wherein acrocentric chromosomes break at their centromeres and the long arms fuse to form a single, large chromosome with a single centromere.

  • Ther is a chromosome count of 45 in balanced carriers and homologous carriers can’t have normal pregnancy
25
Q

Identify the types of segregation which occur in meiosis I

A
  • Alternate
  • Adjacent-1
  • Adjacent-2
26
Q

Describe alternate segregation

A
27
Q

Describe adjacent-1 segregation

A
28
Q

Describe adjacent-2 segregation

A
29
Q

What is FISH?

A

Fluorescent in situ hybridisation is a molecular cytogenetic technique wherein probes are used for specific chromosomes or loci

30
Q

Outline 5 steps ocurring in FISH

A

⇒ Select target material

⇒ Specific DNA probe (fluorescent label)

⇒ Denaturation & hybridisation

⇒ Washing

⇒ Visualisation

31
Q

What are the different types of FISH probes?

A
32
Q

Describe the use of microarray comparative genomic hybridisation (aCGH)

A
  • Examines the whole genome at high resolution
  • Uses patient DNA not chromosomes
  • Compares normal control DNA to patient DNA
  • Can’t detect balanced rearrangements
  • Not used for mutation detection
33
Q

What are the aCGH referral groups?

A
  • Learning difficulties
  • Developmental delay
  • Multiple congenital abnormalities
  • Normal karyotype
  • Balanced / unbalanced karyotype
34
Q

What are the advantages and disadvantages of aCGH?

A
  • Advantages: examines entire genome, detailed information on genes in del/dup region
  • Disadvantages: more expensive than karyotyping, doesn’t detect balanced rearrangements, mosaicism may be missed