Nuclear DNA v mtDNA: Principles of inheritance

.

Low level of mutation:

Healthy child

Intermediate level of mutation: Mild disease

High level of mutation:

Severe disease

‘Mother’ cell containing

mutant mtDNA

Mother: ‘unaffected’ carrier

Father: ‘unaffected’ carrier

‘unaffected’ child: 1 in 4 chance

‘unaffected’ carrier child: 2 in 4 chance

‘affected’ child: 1 in 4 chance

- This example represents an autosomal recessive disease - Both parents have one ‘healthy’ gene, and one ‘disease’ gene; as the ‘healthy’ gene over-rides the ‘disease’ gene, the parents are healthy - There is a ¼ chance that their children will carry two copies of the ‘healthy’ gene, a ½ chance their children will carry one copy of the ‘healthy’ gene, and one copy of the ‘disease’ gene, and will be healthy like the parents, and ¼ chance they will inherit two copies of the ‘disease’ gene. In this case, the child will inherit the disease

- The mother may have a mixed population of mitochondria that contain ‘normal’ mtDNA and ‘mutated’ mtDNA that causes disease; this is called heteroplasmy - If heteroplasmy is present in pre-cursor egg cells, the daughter egg cells may have mitochondria containing a differing contribution of ‘healthy’ and mutated mtDNA - One factor in the severity of disease is the proportion of ‘normal’ mtDNA in relation to ‘mutated’ mtDNA; the more mutated mtDNA, the worse the disease

= Normal mitochondria = Mutant mitochondria

= Cell nucleus

Primary oocytes

Mature oocytes

Fertilisation

mtDNA amplification

- Found in the nucleus of the cell - 3,300,000,000 bases arranged in linear chromosomes (above) - Two copies of each chromosome present - Maternally and paternally inherited - Contains approximately 20,000 - 30,000 genes - 93% of the genome contains non-coding DNA

- Found in the mitochondrial matrix - 16,569 bases in a circular chain of DNA - Multiple copies present in each mitochondrion - Maternally inherited - Contains 37 genes that encode

- 13 proteins - 22 tRNAs and 2 rRNAs

- 3% of the genome contains non-coding DNA

Nuclear DNA

Mitochondrial DNA (mtDNA)

Mendelian inheritance Non-Mendelian inheritance