Genetics Flashcards
distinguish metacentric, submetacentric and acrocentric
Metacentric = centromere in the middle
Submetacentric = smaller p arm than q arm
Acrocentric = centromere colse to an end
Tandem repeats of telomeres?
TTAGGG
Form a T loop
When does recombination event occur during meiosis?
At pachytene
Define constitutional mosaicism.
2 cell lines with different chromosomal complements arising from the same zygote.
3 non-mosaic autosomal chromosome trisomies that are compatible with human life?
Trisomy 13 (Patau syndrome)
Trisomy 18 (Edward syndrome)
Trisomy 21 (Down syndrome)
Write the free trisomy
47, XY, +21
Which chromosomes are acrocentric?
13, 14, 15, 21, 22
Etiologies of trisomy 21
95% of cases = free trisomy (extra 21 chromosome)
4% of cases = Robertsonian translocation between chrs 14 and 21.
How do we obtain chromosomes in the metaphase state?
- Blood sample
- Add PHA to stimulate lymphocytes to divide
- Disable mitotic spindle
- Add hypotonic solution to swell cells, fix.
- Drop cell on suspension slide
- Examine chromosome
What is the first line test for couples with recurrent miscarriages?
Chromosome banding
Disadvantages of chromosome banding
Resolution limit
Require actively growing source of cells
Example of gene studied with FISH
SRY gene mutation in Klinefelter syndrome - males with sex reversal because SRY is translocated onto X so appear as XX
Limits of FISH
We only see the region of the chromosome complementary to our probe
Chromosomal microarray use
First line test for fetuses with major malformations on US and patients with unexplained developmental delay or intellectual disabilities, autism, multiple congenital abormalities or dysmorphic features.
Chromosomal microarray main limit
balanced rearrangements are undetected
How does CML arise from translocation?
Translocation takes place between two chromosomes: chromosome 9 and chromosome 22. The BCR-ABL1 fusion gene encodes a mutant protein called BCR-ABL1 tyrosine kinase. This kinase is constitutively active, meaning it is always “turned on” and continuously signals the cell to divide and proliferate.
ABL1 from chr 9 (tyrosine kinase)
BCR from chr 22
Phenylketonuria type of transmission + details
Autosomal recessive.
No conversion from Phe to Tyrosine = accumulation of Phe.
Example of allelic/genetic heterogeneity.
Marfan syndrome type of transmission + details
Autosomal dominant.
Allelic heterogeneity.
Pleiotropy.
Variable expressivity.
Full penetrance.
Symptoms: tall, thin, long fingers, dislocated lenses, heart problems.
25% mutations are denovo
DMD type of transmission + details
DMD = Duchenne muscular dystrophy.
X-linked disease.
1/3 mutations are de Novo.
Genetic lethal.
Progressive muscle weakness, coke-coloured urine, Gower signs, elevated creatine kinase levels.
4 examples of Y-linked genes
-SRY gene
-Excessive hair on ear pinna
-TDF gene (testis determining factor)
-TSPY gene (testes specific protein)
Example of mitochondrial disease
MELAS
Symptoms = encephalophaty, lactic acidosis and stroke-like episodes.
Pleiotropic condition.
Example of trinucleotide repeat disorder
Huntington’s disease (combination of Parkinsons, psychosis and Alzheimer’s).
Most of these disorders are autosomal dominant.
Prader-Willi syndrome etiologies
Loss of normal imprinting: active copy is from the father. Could be due to UPD, mutations or deletions in father copy.
Angelman syndrome etiologies
Loss of normal imprinting: active copy is from the mother. Could be due to UPD, mutations or deletions in mother copy.
