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Nuclear DNA (nDNA) Mitochondrial DNA (mtDNA) - Found in the nucleus of the cell - 3,300,000,000 bases (A, T, C and G) - Arranged in linear chromosomes - Two copies of each chromosome - Maternally and paternally inherited - Contains approximately 20,000 genes - 93% of the genome is non-coding DNA - Found in the mitochondrial matrix - 16,569 bases (A, T, C and G) - Arranged in a circular chain of DNA - Multiple copies present - Maternally inherited - Contains 37 genes - 3% of the genome is non-coding DNA Mendelian inheritance Non-Mendelian inheritance Mother: ‘healthy’ carrier Father: ‘healthy’ carrier ‘healthy’ child: 1 in 4 chance ‘healthy’ carrier child: 2 in 4 chance ‘diseased’ child: 1 in 4 chance - Example of an autosomal recessive disease - Disease severity is correlated to ratio of healthy to diseased mitochondria Healthy mitochondria Low level of mutation: healthy child Intermediate level of mutation: mild disease High level of mutation: severe disease mother cell oocytes Diseased mitochondria with mutated mtDNA Nucleus Nuclear DNA v mtDNA: principles of inheritance

Nuclear DNA v mtDNA: principles of inheritanceNuclear DNA v mtDNA: principles of inheritance 11 17 22 13 14 15 20 10 16 12 18 Normal Karyotype MRC Mitochondrial Biology Unit Created

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Page 1: Nuclear DNA v mtDNA: principles of inheritanceNuclear DNA v mtDNA: principles of inheritance 11 17 22 13 14 15 20 10 16 12 18 Normal Karyotype MRC Mitochondrial Biology Unit Created

NuclearDNA(nDNA) MitochondrialDNA(mtDNA)

- Foundinthenucleusofthecell- 3,300,000,000bases(A,T,CandG)- Arrangedinlinearchromosomes- Twocopiesofeachchromosome- Maternallyandpaternallyinherited- Containsapproximately20,000genes- 93%ofthegenomeisnon-codingDNA

- Foundinthemitochondrialmatrix- 16,569bases(A,T,CandG)- ArrangedinacircularchainofDNA- Multiplecopiespresent- Maternallyinherited- Contains37genes- 3%ofthegenomeisnon-codingDNA

Mendelianinheritance Non-Mendelianinheritance

Mother:‘healthy’carrier

Father:‘healthy’carrier

‘healthy’child:1in4chance

‘healthy’carrierchild:

2in4chance

‘diseased’child:1in4chance

- Exampleofanautosomalrecessivedisease

- Diseaseseverityiscorrelatedtoratioofhealthytodiseasedmitochondria

Healthymitochondria

Lowlevelofmutation:healthychild

Intermediatelevelofmutation:milddisease

Highlevelofmutation:severedisease

mothercell

oocytes

DiseasedmitochondriawithmutatedmtDNA

Nucleus

NuclearDNAvmtDNA:principlesofinheritance