Chromosomal Abnormalities III

Question 1

Epigenetics

Answer 1

mitotically & meiotically heritable variations in gene expression that are not caused by changes in DNA sequence (examples: DNA methylation and PTM of histones)

Question 2

Imprinting silences genes by adding methyl groups where?

Answer 2

CpG dinucleotides in the promoter regions of imprinted genes (allele-specific)

Question 3

When is imprinting established?

Answer 3

In primordial germ cells as part of overall genomic reprogramming; maintained throughout embryogenesis

Question 4

Compare & contrast the genetic differences of Prader-Willi & Angelmann

Answer 4

On chromosome 15q11-q13
If Paternal allele has deletion –> Prader-willi
If Maternal allele has deletion –> angelMann

Loss of the paternal alleles at 15q11-13 → expression of only maternal alleles, some of which are already silenced through methylation → Prader-Willi syndrome

Question 5

Aside from deletion on 15q11-q13, how else can one inherit Prader-Willi?

Answer 5

If maternal gamete is disomic for 15, you have trisomic conceptus (normally inviable)
THEN, mitotic nondisjunction early on “rescues” lethality. But if the lost chromosome is paternally-derived, fetus has 2 maternal alleles.

Question 6

What are the clinical symptoms of Prader-Willi?

Answer 6

Excessive / indiscriminate eating (obesity)
Short stature
Small hands and feet
Hypogonadism
Intellectual disabilities

Question 7

What are the clinical symptoms of Angelmann?

Answer 7

unusual facial appearance
short stature
severe intellectual disabilities
spasticity
seizures