Chromosomal abnormalities Flashcards
What is polyploidy?
- Gain of a whole haploid set of chromosomes resulting in cells being triploid (69,XXX)
- Tetraploidy is rare but can occur
Describe the chromosomal basis of sex determination
- Mother can only produce X gametes, the father can produce either X or Y gametes
- Therefore it is the father who determines the sex during fertilisation as either an X or Y gamete fertilises the oocyte
What is the cause of polyploidy?
-Polyspermi: fertilisation of an oocyte with more than 1 sperm
Is polyploidy viable?
- No, it is fatal and accounts for 15% of all miscarriages
- Term deliveries die shortly after birth
What is aneuploidy?
-Loss or gain of single whole chromosomes
How does aneuploidy occur?
-Originates from non-disjunctions of a single chromosome at one of the meiotic cell divisions
What does non-disjunction produce?
-One gamete with a chromosome missing and one gamete with an extra chromosome
What is produced if non-disjunction occurs at a mitotic cell division?
- Mosaicism. ie two cell populations in an individual
- One cell like will be normal and the other will exhibit aneuploidy
What 4 gametes are produced if non-disjunction occurs at meiosis I?
-Two gametes with an extra copy and Two gamete missing a copy
What are the 4 possible zygote genotypes produced when gametes produced from non-disjunction at meiosis I undergo fertilisation with a normal gamete?
- 2 Trisomy gametes
- 2 monosomy gametes
What 4 gametes are produced if one non-disjunction occurs at meiosis II?
- 2 normal gametes from the daughter cell which didn’t undergo non-disjunction
- 1 gamete with an extra copy of a chromosome
- 1 gamete missing a chromosome
What are the 4 possible zygote genotypes produced when gametes produced from non-disjunction at meiosis II undergo fertilisation with a normal gamete?
- 2 normal zygotes
- 1 zygote with monosomy
- 1 zygote with trisomy
What is trisomy?
-Cells have an extra copy of one chromosome
What is monosomy?
-Cells have a missing copy of a chromosome
What is anaphase lag?
- Chromosomes can get ‘left behind’ at cell division due to defects in spindle fibre attachment to chromosomes
- The lagging chromosome may be lost entirely
Does anaphase lag happen in meiosis or mitosis?
-Both, it can happen at any stage
What is down syndrome?
-Trisomy 21 -> cells have an extra copy of chromosome 21
What are the signs and symptoms of down syndrome?
- Hypotonia
- Characteristic facial features
- Intellectual disability
- Heart defects
- Increased prevalence of leukaemia
What is Edwards syndrome?
-Trisomy 18-> cells have an extra copy of chromosome 18
What causes Edward’s syndrome?
-Maternal meiosis II error
Is edwards syndrome viable?
-No, model lifespan is 5-15 days
What are the signs and symptoms of edwards syndrome?
- Small lower jaw
- Low set ears
- Rockerbottom feet
- Overlapping fingers
What is patau syndrome?
-Trisomy 13 -> cells have an extra copy of chromosome 13
Is patau syndrome viable?
-No, majority die in neonatal period
What are the signs and symptoms of patau syndrome?
- Multiple congenital abnormalities
- Polydactyly (extra toes etc0
- Holosencephaly
What is Turner syndrome?
-Monosomy X ->majority of cases is absent paternal X
What are the signs and symptoms of Turners syndrome?
- Only effects females
- Short stature
- Heart defects
- Neck webbing
- Mild learning disability
What is Klinefeller syndrome?
-Trisomy X in males
What is the cause of mosaicism?
-Mitotic non-disjunction
What happens is the mitotic non-disjunction occurs at the first zygotic division?
-No mosaicism is exhibited, looks like non-disjunction meiotic event and will produce aneuploidy
What happens if mitotic non-disjunction occurs at a division ofter the fist zygotic event?
- Generation of 3 cells lines, normal, Trisomy and monosomy
- Monosomy usually lost
What is uniparental disomy?
-Presence of homologous chromosomes from one parent
What are the 3 forms of uniparental disomy?
- Isodisomy -> 2 identical chromosomes from one parent
- Heterodisomy -> 2 homologous chromosomes from one parent (most common form and occurs from meiosis I error)
- Segmental UPD-> Only part of the chromosome involved
What is the genetic result of uniparental disomy?
-The homologous chromosomes have not been imprinted and therefore the chromosome involved has no phenotypic effect
Name 3 diseases caused by UPD
- Prader-willi/angelman syndrome(15)
- Russel-Silver(7)
- Beckwith-Wiedemann(11)
What is a chromosomal translocation?
-A chromosome abnormality caused by rearrangements of parts between non-homologous chromosomes during meiotic disjunctions
What are the two types of translocation?
- Reciprocal
- Robertsonian
What is meant by a balanced translocation?
-There is even exchange of material with no genetic material extra or missing
What is meant by an unbalanced translocation?
-Exchange of chromosome material is unequal producing extra or missing genetic material in cells
What causes reciprocal translocations?
-Meiotic disjunction with a two-break rearrangement to produce a carrier
What is the consequences of being a carrier of a reciprocal translocation?
-There is an increased risk of producing gametes with balanced and unbalanced segregations
What possible segregations can occur in carriers of reciprocal translocations?
May need paper!
- Alternate-> Alternate chromosomes have segregated together producing balanced gametes
- Adjacent 1-> non-homologous chromosomes have segregated together producing gametes with extra chromosomal material of one chromosome and only the small loss of the other chromosome
- Adjacent 2-> homologous chromosomes have segregated together resulting in almost an entire extra copy of one chromosome and almost entire loss of the other
What is a robertsonian translocation?
-Meiotic disjunction where two acrocentric chromosomes fuse together producing a carrier with a chromosome count of 45 due to fusion
What is the consequences of being a robertsonian translocation carrier?
-Phenotypically normal but with increased risk of producing aneuploidy gametes
In reciprocal translocations, what structure forms during meiosis?
-Quadrivalent
In robertsonian translocations, what structure forms during meiosis?
-Trivalent
If a person carries a 14:21 robertsonian translocation, what is the possible genotype of the zygotes produced after fertilisation with a normal gamete? (monosomy, trisomy normal)
May need some paper!
- Normal
- Balanced carrier
- Trisomy 14
- Monosomy 14
- Monosomy 21
- Trisomy 21
Why do deletions of chromosome segments occur?
-Due to uneven pairing or recombination
Are deletions balanced or unbalanced?
-Unbalanced
What is karyotyping?
-Systematic sorting of metaphase chromosomes by staining, pairing up and counting
Why is a stain used which highlights the banding pattern of chromosomes?
-So each chromosome can be checked for abnormalities
How are chromosomes reported by karyotyping?
-Chromosome number, sex complement, structural changes
-Separated by commas
-eg 46XX-normal female
47,XX,+21-female with trisomy 21
What are the possible reasons for karyotype refferals?
Constitutional abnormalities: -Prenatal diagnosis -Birth defects -Infertility -Abnormal sexual development -Recurrent foetal loss Acquired abnormalities -Leukaemias -Solid tumours -Prognostic information on therapy type
What is FISH?
-Fluorescence in situ hybridisation
When is FISH used?
- To identify specific chromosomes or loci (need to know what you are looking for)
- To identify duplications or deletions of genetic material
How is FISH carried out?
- Fluorescently labelled DNA probe hybridised with target material
- Washed
- Visualised using fluorescent microscope
When are chromosome paints used?
-To identify translocations
