Nuclear DNA v mtDNA: Principles of inheritance
Nuclear DNA Mitochondrial DNA (mtDNA)
- Found in the nucleus of the cell - Found in the mitochondrial matrix - 3,300,000,000 bases arranged in linear chromosomes - 16,569 bases in a circular chain of DNA (above) - Multiple copies present in each mitochondrion - Two copies of each chromosome present - Maternally inherited - Maternally and paternally inherited - Contains 37 genes that encode - Contains approximately 20,000. - 30,000 genes - 13 proteins - 93% of the genome contains non-coding DNA - 22 tRNAs and 2 rRNAs - 3% of the genome contains non-coding DNA
Mendelian inheritance Non-Mendelian inheritance Mother: Father: = Cell nucleus ‘unaffected’ carrier ‘unaffected’ carrier = Normal ‘Mother’ cell mitochondria containing = Mutant mutant mitochondria mtDNA
Primary oocytes
mtDNA amplification ‘unaffected’ child: ‘unaffected’ carrier child: ‘affected’ child: 1 in 4 chance 2 in 4 chance 1 in 4 chance Mature oocytes
- This example represents an autosomal recessive disease Fertilisation - Both parents have one ‘healthy’ gene, and one ‘disease’ gene; as the ‘healthy’ gene over-rides the ‘disease’ gene, Low level of Intermediate level High level of mutation: of mutation: mutation: the parents are healthy Healthy child Mild disease Severe disease - There is a ¼ chance that their children will carry two copies of the ‘healthy’ gene, a ½ chance their children will - The mother may have a mixed population of mitochondria carry one copy of the ‘healthy’ gene, and one copy of the that contain ‘normal’ mtDNA and ‘mutated’ mtDNA that ‘disease’ gene, and will be healthy like the parents, and ¼ causes disease; this is called heteroplasmy chance they will inherit two copies of the ‘disease’ gene. In - If heteroplasmy is present in pre-cursor egg cells, the this case, the child will inherit the disease 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