S14) Chromosomal Mutations Flashcards
What is cytogenetics?
Cytogenetics is the study of the genetic constitution of cells through the visualisation and analysis of chromosomes
What are the benefits of cytogenetic analysis?
- Accurate diagnosis/prognosis of clinical problems
- Better clinical management e.g. hormone treatment for Klinefelter syndrome
- Prenatal diagnosis
- Assess future reproductive risks
In terms of constitutional abnormalities, identify some referral reasons for cytogenetic analysis
- Prenatal diagnosis
- Birth defects
- Abnormal sexual development
- Infertility
- Recurrent foetal loss
In terms of acquired abnormalities, identify some referral reasons for cytogenetic analysis
- Leukaemia’s (acute/chronic diseases)
- Solid tumours
- Specific translocations/abnormalities
Identify and describe two prenatal diagnostic methods
Identify 4 birth defects
- Dysmorphism
- Congenital malformations
- Mental retardation
- Developmental delay
Which three biochemical techniques are used in cytogenic analysis?
- Karyotyping
- Fluorescent in situ hybridisation (FISH)
- Microarray comparative genomic hybridisation (aCGH)
Briefly describe the process of karyotyping (chromosome analysis)
Karyotyping is the systematic sorting of chromosomes:
⇒ Whole genome screen
⇒ Metaphase chromosomes stained, paired up, grouped together
⇒ Abnormalities described using standard nomenclature
Outline the steps involved in chromosome analysis
⇒ Count the number of chromosomes
⇒ Identify each chromosome pair
⇒ Assess any missing/extra material
⇒ Recheck all chromosomes independently
Provide examples of standard nomeclature for the following:
- Normal female
- Normale male
- Female with trisomy 21
- Male with chromosome 7 inversion
- 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)
Aneuploidy is a numerical cytogenetic abnormality.
Define it
Aneuploidy is the loss/ gain of whole chromosomes and arise due to errors at cell division in meiosis
Identify some examples of aneuploidy where whole chromosomes are lost and identify their associated diseases
- Trisomies – Down syndrome +21, Patau syndrome +13 and Edwards syndrome +18
- Monosomies – Turner syndrome 45,X (X inactivation)
What is polyploidy?
Polyploidy is the gain of a whole haploid set of chromosomes (an example of aneuploidy) eg. triploid 3n – 69, XXX
What are the causes of polyploidy?
The most common cause of polyploidy is polyspermy i.e. fertilisation of an egg by more than one sperm
Aneuploidy is due to non-disjunction during cell division.
Describe how this occurs