Session 16-Chromosome Abnormalities Flashcards
What is cytogenetics?
Study of genetic constitution of cells through the visualisation and analysis of chromosomes
Why do cytogenetic analysis? (4)
- Accurate diagnosis/prognosis of clinical problems
- Better clinical management
- Assess future reproductive risks
- Prenatal diagnosis
How many miscarriages counts as ‘recurrent foetal loss’?
3 or more
What are the two types of referral reasons?
Constitutional abnormalities
Acquired abnormalities
What are the types of constitutional abnormalities? (5)
Prenatal diagnosis Birth defects Abnormal sexual development Infertility Recurrent foetal loss
What are the types of acquired abnormalities? (3)
- Leukaemias:
Acute disease-AML/ALL (acute myeloid/lymphoblastic leukaemia)
Chronic disease-CML (chronic myeloid leukaemia)
Myelodysplasia/myeloproliferative disorders - Solid tumours
- Specific translocations/abnormalities
What are the two main methods of prenatal diagnosis?
- Chorionic villus sampling-at end of first trimester of pregnancy
- Amniocentesis-2nd trimester
Why do prenatal diagnosis? (5)
- Maternal serum screening for Down’s syndrome-blood sample taken at around 15 weeks, biochemical markers are measured
- First trimester screening
- FH chromosome abnormality
- Abnormal ultrasound scan
- DNA studies
What are some examples of birth defects? (5)
- Dysmorphism
- Congenital malformations
- Mental retardation
- Development delay
- Specific syndromes:
Down syndrome (trisomy 21)
Williams syndrome
DiGeorge syndrome
What is karyotyping?
Systemic sorting of chromosomes
What is aneuploidy?
Loss and gain of whole chromosomes due to errors at cell division in meiosis
Give three examples of trisomies
Down Syndrome +21
Patau syndrome +13
Edwards +18
Give an example of a monosomy
Turner syndrome 45,X (X inactivation)
What is polyploidy?
Gain of a whole haploid set of chromosomes
What is the cause of polyploidy?
Polyspermy=fertilisation of an egg by more than one sperm
What are the causes of aneuploidy?
Originates from non-disjunction at one of the meiotic cell divisions and forms gametes with a missing chromosome and an extra chromosome
True or false: aneuploidy can occur during mitotic cell division
TRUE
What does aneuploidy in mitotic cell division cause?
Mosaicism ie two cell populations in an individual
What are the characteristics of Down syndrome? (6)
Hypotonia Characteristic facial features Intellectual disability Heart defects Increased prevalence of leukaemia Increased incidence of early Alzheimer's
What are some of the signs of Edwards syndrome? (4)
Small lower jaw
Low-set ears
Rocker bottom feet
Overlapping fingers
What is X chromosome inactivation?
Only one X chromosome is ever active in a human cell
Why is a single X chromosome a problem?
X and Y chromosomes have short regions in common at the tips of the long and short arms (PAR1 in Y and PAR2 in X) and this allows for pairing during cell division. Turner syndrome patients will be monosomic for genes in the PARs
Which gene is associated with short stature?
SHOX (within PAR)
What are the signs of Turner syndrome? (6)
Puffy feet Redundant skin at back of neck Short stature Heart defects Mild learning difficulties Infertility
What is mosaicism?
Presence of two or more cell lines in an individual
What are the two types of translocations?
Reciprocal
Robertsonian
What are the different types of cytogenetic structural abnormalities? (8)
Translocations Inversions Deletions Duplications Insertions Rings Marker chromosomes Isochromosomes
What are isochromosomes?
Mirror image chromosomes
What are the two types of inversions?
Paracentric
Pericentric
What are reciprocal translocations?
Two break rearrangements - exchange of material between nonhomologous chromosomes
What are the types of mal-segregation in meiosis?
Adjacent 1-non homologous centromeres move together to daughter cell
Adjacent 2-homologous centromeres
3:1 non disjunction
4:0 non disjunction
What does FISH stand for and what is it?
Fluorescent in situ hybridisation
Molecular cytogenetic technique
What are the different types of FISH probes? (4)
- Locus/gene specific probes
- Centromere probes
- Telomere probes
- Whole chromosome paints
What are centromere probes used for and what are their characteristics?
Large probes, easy to see metaphase and interphase
Used for: identifying derivative chromosomes and markers
What are whole chromosome paints used for?
To identify individual chromosomes even when they are rearranged
What are locus specific probes used for?
Microdeletion/duplication syndromes
What does microarray comparative genomic hybridisation (aCGH) examine?
Whole genome at high resolution
What are the advantages of aCGH? (5)
- Examines entire genome and high resolution
- Targeted against known genetic conditions
- One array is equivalent of many FISH investigations
- Detailed info on genes in del/dup region
- Better phenotype/genotype correlation
What are the disadvantages of aCGH? (4)
- Arrays more expensive than karyotyping
- Won’t detect balanced rearrangements
- Copy number variation
- Mosaicism may be missed
What is copy number variation?
Sections of genome are repeated and number of repeats in genome vary between individuals
