S14) Chromosomal Mutations Flashcards
(34 cards)
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
What is anaphase lag?
- 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
What is Down syndrome?
- 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
What is Edwards syndrome?
- 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
What is Patau syndrome?
- 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
What is Turner’s Syndrome?
- 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
What is mosaicism?
- 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
Identify 5 cytogenetic structural abnormalities
- Translocations
- Inversions
- Deletions
- Duplications
- Insertions
What are recipocial translocations?
- 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
What are robertsonian translocations?
- 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
