What is the most crucial building block of medical genetics?
The phenotype. All genetics questions start here.
What is cytogenetics?
The examination of chromosomes for physical rearrangements
What are the two type of rearrangements in chromosomes?
Germline and somatic
What are the 3 major cytogenetics techniques?
- G banding (majority)
- fluorescent in situ hybridization (FISH)
- More recently, comparative genomic hybridisation (CGH)
Describe the G banding Technique.
- It uses metaphases chromosomes
- Trypsin treatment strips off the histones (reveal DNA)
- stain with Giesma
- Binds to A-T sequence (chromatin dense and gene poor)
What is R-banding?
The inverse of G-banding (gene rich, stain with chromomycin)
What is a karyotype
The image and description of a chromosomal compliment
What are you looking for from G-banding?
A visible karyotype. Large structural changes, as they can give insight into specific gene locations and specific diseases.
What are translocations?
Exchange between non-homologous chromosomes
What does the exchange of centric and acentric fragments cause?
Dicentric + acentric chromosomes. It is not stable in mitosis.
What does the exchange of 2 acentric fragments cause?
Stable reciprocal translocation. Somewhat common in healthy humans.
What does exchange in proximal short arms cause?
Stable Robertsonian Translocation, one chromosome is lost, one formed between attached chromosomes
What happens in meiotic non-disjunction?
If it occurs at meiosis II and not I, one gamete has 24 chromosomes, one has 22. If it doesn’t occur at either meiosis both gametes are normal. If it occurs at meiosis I, 2 gametes will have 24, 2 will have 22
Prevalence of down syndrome?
1:800/1000 live births
What causes down syndrome?
Chromosomal non-disjunction
Symptoms of Fragile X syndrome?
Moderate to severe mental retardation.
Macroorchidism (Large testicles)
Distinct facial features, long face, large ears, prominent jaw
In some cases Autism/Aspergers ADHD
What is the prevalence of Fragile X syndrome?
Half of X-linked mental retardation cases. Second most common cause of mental impairment after trisomy 21.
1:4000 in boys, 1:8000 in girls (Despite being an X-linked condition)
Pathology of Fragile X?
- Caused by unstable expansion of (CGG)n repeat in FMR1 gene
- Abnormal methylation, which results in suppression of FMR1 transcription and decreased protein levels in the brain
What is the phenotype for Chronic Myeloid Leukemia (CML)?
- Cancer of the WBCs
- Up regulated growth of myeloid cells in bone marrow
- Anemia
- Increased susceptibility to infections
- Low platelet count
- Blast crisis (after additional mutations)
What is the abnormality in CML and where is it seen?
On chromosome 22, known as the Philadelphia Chromosome, there is a translocation with chromosome 9. Likely due to homologous sections on both chromosomes.
