Gene Dosage Imprinting

Question 1

What is anueploidy?

Answer 1

Unbalanced set of chromosomes due to excess or deficiency or individual chromosomes

Question 2

When does anueploidy most often arise?

Answer 2

By non-dysjunction of 2 homologous chromosomes or sister chromatids during cell division, either in meiosis or mitosis.

Question 3

What is haploinsufficiency?

Answer 3

Where a single copy of some critical genes is not sufficient to support normal cell function and hence fetal development. I.e. 50% normal protein levels are not enough.

Question 4

What is epigenetics?

Answer 4

Changes in gene expression, with no change in DNA sequence.

Question 5

What are the 3 main ways in which epigenetics regulates?

Answer 5

1) DNA methylation
2) Histone modification
3) Gene silencing through non-coding RNAs

These systems interact and stabilise each other.

Question 6

What is X- chromosome inactivation

Answer 6

• One of the 2 X chroms is inactivated in females as a gene dosage mechanism to make sure that the level of expression of X- linked genes is equal in males and females.

Question 7

What are the main ways that the is X- chromosome can be inactivated?

Answer 7

• On the X- chromosome which is to be inactivated- there is expression of a ncRNA called Xist (X inactivation) and it is made at a particular region of a chromosome and then creates a wave of hyperchromatin.
• So moves across in both directions from where it has been expressed.
• Also have DNA methylation

Question 8

Is X chrom inactivation usually permanent?

Answer 8

Yes and also usually heritable through cell divisions

Question 9

What does Turner Syndrome tell us about X inactivation?

Answer 9

Some genes escape X inactivation (i.e. transcriptionally active from both X chroms)

Question 10

genomic imprinting

Answer 10

Is the process whereby the parental origin of a particular gene is ‘marked’ by a reversible epigenetic mechanism:

• DNA methylation
• Chromatin condensation
• ncRNAs

Question 11

what do maternally expressed genes do?

Answer 11

Limit fetal growth

Question 12

what do paternally expressed genes do?

Answer 12

promote fetal growth

Question 13

What are some of the genetic and epigenetic changes that underlie recognised imprinting disorders?

Answer 13

• Large deletions/ duplications of chromosome regions that contain imprinted genes–> Loss of heterozygosity
• Uniparental disomy
• Alteration in epigenetic marks at imprinted loci, without alterations in DNA sequence (epimutation)
• DNA mutations in genes that are usually imprinted or on imprinting control centres.