Chromosomal Abnormalities Flashcards
What is Cytogenetics?
Study of genetic constitution of cells through the visualisation and analysis of chromosomes
Why do cytogenetic analysis?
Accurate diagnosis, better clinical management, assess future reproductive risks, prenatal diagnosis
Why might you be referred for cytogenetics?
Constiutional abnormalities, prenatal disagnosis, birth defects, abnormal sexual development, infertility, recurrent fetal loss, leukaemia, solid tumours, specific translocations/abnormalities
What are the two types of prenatal diagnosis?
Chorionic villus and Amniocentesis
What can be seen in prenatal diagnosis?
Maternal screening for down syndrome, first trimester screening, FH chromosome abnormality, Abnormal ultrasound scan, DNA studies
What birth defects can be seen on prenatal scan?
Dysmorphism, congenital malformations, mental retardation, developmental delay, specific syndromes like down, williams and digeorge syndrome,
At what stage are chromosomes karyotypes?
Metaphase
How do you analyse chromosomes?
Count the number of chromosomes, identify each chromosome pair, assess if there is any missing or extra material,must be seen at correct resolution twice and be independently rechecked once
How do you describe a karyotype?
chromosome number, sex complement and structural changes, separated by commas e.g. 46, XX- normal female
What are Trisomies?
Extra chromosome e.g. down syndrome
What are monosomies?
Less chromosomes e.g. turner syndrome
What is polyploidy?
Gain of a whole haploid set of chromosomes
What causes polyploidy?
polyspermy- when an egg is fertilised by more than one sperm
What is anaphase lag?
Chromosomes left behind and not pulled to poles
What are the symptoms of down syndrome?
Hyptonia, characteristic, facial features, heart defects, increased chance of leukaemia, alzeimers
Which chromosome is trisomy in down syndrome?
21
What chromosome is trisomy in Edwards syndrome?
18
What are the symptoms of Edwards Syndrome?
Small lower jaw, prominent occiput, low-set ears, rocker bottom feet, overlapping fingers, live 5-15 days
What chromosome is Trisomy in Patau syndrome?
13
What is X chromosome inactivation?
One X chromosome is ever active in a human cell
Why does Turners syndrome occur?
Monosonic for genes in the Par regions
What are the symptoms of Turners syndrome?
Puffy feet, redundant skin at back of neck, short, heart defects, mild learning difficulties, neck webbing, infertile
What is Mosaicism?
Presence of two or more cell lines in an individual
What usually causes mosaicism?
Mitotic non-disjunction
What is a reciprocal translocation?
Two break arrangement, carriers will produce balanced and unbalanced gametes, will have abnormal phenotype if unbalanced
What are the types of secregation in Meiosis?
Alternate- balanced Adjacent 1- non homologous centromeres Adjacent 2- homologous centromeres 3:1 non disjunction 4:0 non disjunction
How do you assess unbalanced segregation outcomes?
Establish the likely segregation, see if the imbalances have been reported before, quote risk if established
What is a robertsonian translocation?
Two afrocentric chromosomes fused together- carrier is phenotypically normal but child will not be
When does prenatal aneuploidy screening take place?
Interphase
What occurs in prenatal aneuploidy screening?
14 days in culture which causes anxiety, FISH
What can microarray not detect?
Balanced rearrangments
Who would be referred for a microarray?
learning difficulties, normal karyotype to see if its really balanced and unbalanced karyotypes to assess gene control
What are the positives of microarray?
examines whole genome at a high resolution, targeted against known genetic conditions, equivalent to 1000s of fish investigations, detailed info on del/dup regions, better phenotype and genotype correlation
What are the negatives of microarray?
more expensive than karyotyping, do not detect balanced rearrangements, masaicism may be missed, copy number variation
How do deletions and duplications arise?
Uneven pairing and recombination during meiosis
How would you report abnormal chromosome results?
Give the ISCN
Describe abnormality in works and what it means, relate to clinical problem, request family samples if requires, refer to clinical genetics, provide appropriate literature
What is Uniparental disomy?
Homologous chromosomes from one parent
Why is UPD a problem?
Imprinting
What syndromes are caused by UPD?
Prader-willi, Russell-Silver and Beckwith-Wiedemann
How does UPD occur?
Trisomy rescue, monosomy rescue, gamete complementation, mitotic error
What is NGS?
Next generation sequencing- sequence fragments in parallel, reveals entire genomes DNA
What are the positive of NGS?
Increased read length, high throughput, automated workflow, simplified protocols
What are the negatives of NGS?
Whole genome sequencing costs high, insufficient IT capacity, lack of knowledge to fully interpret findings, ethically
How is non-invasive prenatal testing done?
Uses cell free metal DNA in maternal plasma
What are liquid biopsies used for?
Non invasive cancer testing
