Non-Mendelian inheritance, complex traits and personalized medicine

Question 1

What kind of inheritance is Mitochondrial inheritance

Answer 1

non-mendelian inheritance

Question 2

What is the mitochondrial DNA?

Answer 2

• Small single circular DNA
• 37 genes: tRNAs, ribosomal RNAs, proteins that encode respiratory chain complexes required for cellular energy (ATP) production

Question 3

What happens when there is a low level of mitochondrial mutation ?

Answer 3

Cell can compensate for reduced normal mtDNA, until a certain threshold is met

Question 4

When does a disease occurs in the case of a mitochondrial mutation?

Answer 4

• Disease occurs when enough cells in a tissue are affected
• Threshold depends upon specific mutation and cell types, eg neurons have lower threshold for disease state

Question 5

Characteristics of Mitochondrial inheritance

Answer 5

• Mitochondria are inherited from the mother
• all offspring of an affected or carrier demale are at risk of being affected
• all daughters of an affected or carrier female care at risk of transmitting the condition
• Affected males cannot pass the condition to any of their children

Question 6

What are the treatment for mitochondrial mutation related disease?

Answer 6

No good treatment for these diseases.

• Try to recover mitochondrial function: add cofactors (vitamins) required for respiratory chain complexes?

Question 7

Is prenatal diagnosis and pre-implantation genetic diagnosis possible with a mitochondrial mutation?

Answer 7

Nop. Cells, tissues vary in level of disease

Question 8

What option to decrease the chance of passing down mitochondrial mutation?

Answer 8

• Mitochondrial donation (“3rd parent IVF”)

Transfer mother’s nuclear DNA into a donated egg with healthy mitochondria (but with the donor’s nuclear DNA removed).
Controversial. How to define “personhood”?

Question 9

Types of non-medelian inheritance

Answer 9

• mitochondrial mutation
• unstable nucleotide repeat disorders
• Genomic imprinting

Question 10

Characteristic of unstable nucleotide repeat disorders

Answer 10

• Some genes contain regions of trinucleotide repeats (CAG, CCG, etc.)
• These repeats are unstable and can expand during meiosis.
• In a disease-specific manner, repeat sizes beyond a certain threshold lead to disease.
• Most are autosomal dominant.

Question 11

Example of a mitochondrial disease

Answer 11

MELAS:Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes

Question 12

Example of a unstable nucleotide repeat disorders

Answer 12

Huntingdon disease

Question 13

What is genomic imprinting

Answer 13

• We inherit one copy of each chromosome from each parent.
• On some chromosomes, there are regions where gene transcription occurs only from one chromosome, either the maternal or the paternal
• The corresponding parental chromosome region is silenced by methylation.
• This parent-specific gene expression is called genomic imprinting.
• A reversible form of gene inactivation - not considered a mutation.

Question 14

What is uniparental disomy (UPD)

Answer 14

A gene having the chromosomes of the same parent’s genes.