Lecture 22-Genomic imprinting and dynamic mutation

Question 1

epigenetic trait

Answer 1

stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence like adding methyl groups to cytosines at the start of genes.

Question 2

imprinting

Answer 2

restriction to either the maternal or paternal allele in the somatic diploid cell of embryos and adults-only occurs in either the DNA inherited from mother or DNA inherited from father, not both
an epigenetic phenomenom
causes different expression from genetically identical alleles
operates at a transcriptional level: allele specific epigenetic modification

Question 3

syndromes caused by abnormalities in imprinted genes

Answer 3

changes to 15q11-q13 cause both syndromes but whether it is maternal or paternal will give either syndrome.
Prader-willi syndrome-70% have deletion of paternal copy

Angelman syndrome-60% have deletion of maternal copy

Question 4

Prada-Willi syndrome

Answer 4

• Failure to thrive in infancy and earlychild hood
• Neonatal hypotonia
• Rapid weight gain after 1 year
• Behavioural obesity and short stature
• Almond-shaped eyes
• Hypogonadism
• Small hands and feet
• Skin hypo pigmentation
• Behavioural problems

loss of paternal segment of chromosome 15q11-q13
for those genes affected in PWS, the maternal copy is usually imprinted (and therefore silenced)

Question 5

Angelman Syndrome

Answer 5

• Open-mouthed expression
• Tongue thrusting
• Mental retardation
• Motor retardation, jerky movements
• Ataxia
• Hypotonia
• Seizures
• Sleep disturbances
• Happy children,laugh frequently
• Skin hypo pigmentation

loss of maternal segment of chromosome 15q11-q13
for those genes affected in AS, the paternal copy is usually imprinted (and therefore silenced)

Question 6

Uniparental disomy

Answer 6

Uniparental disomy = embryo inherits 2 copies of a locus from one parent and none from the other parent ). In the case of AS and PWS it’s the same process is the copies are imprinted or missing the genes

Question 7

Role of DNA methylation in imprinting

Answer 7

Methylation of DNA in mammalian cells occurs at cytosine residues in CpG islands
CpG methylation of promotors causes silencing
CpG methylation transmitted through cell division by maintenance of methyl transferase activity- can be reversed during development
gamete specific methylation (male or female not both) mediated by gamete specific proteins binding imprinted genes during gametogenesis and early embryogenesis.

Question 8

female and male imprinting is established when

Answer 8

during oocyte maturation

prior to meiosis in the post-mitotic primary spermatocyte