Genetics

Question 1

distinguish metacentric, submetacentric and acrocentric

Answer 1

Metacentric = centromere in the middle
Submetacentric = smaller p arm than q arm
Acrocentric = centromere colse to an end

Question 2

Tandem repeats of telomeres?

Answer 2

TTAGGG
Form a T loop

Question 3

When does recombination event occur during meiosis?

Answer 3

At pachytene

Question 4

Define constitutional mosaicism.

Answer 4

2 cell lines with different chromosomal complements arising from the same zygote.

Question 5

3 non-mosaic autosomal chromosome trisomies that are compatible with human life?

Answer 5

Trisomy 13 (Patau syndrome)
Trisomy 18 (Edward syndrome)
Trisomy 21 (Down syndrome)

Question 6

Write the free trisomy

Answer 6

47, XY, +21

Question 7

Which chromosomes are acrocentric?

Answer 7

13, 14, 15, 21, 22

Question 8

Etiologies of trisomy 21

Answer 8

95% of cases = free trisomy (extra 21 chromosome)
4% of cases = Robertsonian translocation between chrs 14 and 21.

Question 9

How do we obtain chromosomes in the metaphase state?

Answer 9

1. Blood sample
2. Add PHA to stimulate lymphocytes to divide
3. Disable mitotic spindle
4. Add hypotonic solution to swell cells, fix.
5. Drop cell on suspension slide
6. Examine chromosome

Question 10

What is the first line test for couples with recurrent miscarriages?

Answer 10

Chromosome banding

Question 11

Disadvantages of chromosome banding

Answer 11

Resolution limit
Require actively growing source of cells

Question 12

Example of gene studied with FISH

Answer 12

SRY gene mutation in Klinefelter syndrome - males with sex reversal because SRY is translocated onto X so appear as XX

Question 13

Limits of FISH

Answer 13

We only see the region of the chromosome complementary to our probe

Question 14

Chromosomal microarray use

Answer 14

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.

Question 15

Chromosomal microarray main limit

Answer 15

balanced rearrangements are undetected

Question 16

How does CML arise from translocation?

Answer 16

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

Question 17

Phenylketonuria type of transmission + details

Answer 17

Autosomal recessive.
No conversion from Phe to Tyrosine = accumulation of Phe.

Example of allelic/genetic heterogeneity.

Question 18

Marfan syndrome type of transmission + details

Answer 18

Autosomal dominant.
Allelic heterogeneity.
Pleiotropy.
Variable expressivity.
Full penetrance.

Symptoms: tall, thin, long fingers, dislocated lenses, heart problems.

25% mutations are denovo

Question 19

DMD type of transmission + details

Answer 19

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.

Question 20

4 examples of Y-linked genes

Answer 20

-SRY gene
-Excessive hair on ear pinna
-TDF gene (testis determining factor)
-TSPY gene (testes specific protein)

Question 21

Example of mitochondrial disease

Answer 21

MELAS
Symptoms = encephalophaty, lactic acidosis and stroke-like episodes.

Pleiotropic condition.

Question 22

Example of trinucleotide repeat disorder

Answer 22

Huntington’s disease (combination of Parkinsons, psychosis and Alzheimer’s).
Most of these disorders are autosomal dominant.

Question 23

Prader-Willi syndrome etiologies

Answer 23

Loss of normal imprinting: active copy is from the father. Could be due to UPD, mutations or deletions in father copy.

Question 24

Angelman syndrome etiologies

Answer 24

Loss of normal imprinting: active copy is from the mother. Could be due to UPD, mutations or deletions in mother copy.

Question 25

Mechanisms of epigenetic diseases

Answer 25

DNA methylation at CpG dinucleotides
Covalent modifications to histone proteins
Regulation by noncoding RNAs