Explain why people with mitochondrial complex I deficiency may have muscle weakness and difficulty with nervous coordination of movement.
When mitochondrial complex I deficiency results from a mutation in mtDNA: - a cell in an ovary produces gametes containing different proportions of normal mitochondria and mitochondria carrying the mtDNA mutation (mutant mitochondria) - a person shows disease symptoms when the proportion of mutant mitochondria in their cells goes beyond a certain threshold - the seriousness of disease symptoms, and the age when they first appear, may vary widely among the children of one woman. In a family with a history of mitochondrial complex I deficiency caused by a mutation in a nuclear gene, the chance of a child inheriting the mutation can be calculated. Suggest why, in families where mitochondrial complex I deficiency is caused by mtDNA mutation, it is not possible to predict the probability of a child inheriting the mutation.
Genetic screening may be used for people showing symptoms of mitochondrial complex I deficiency. At first, 7 mtDNA genes and 37 nuclear genes were sequenced. Some of the people tested had no mutations in any of these genes. As a consequence, another gene was sequenced in these people and was found to be mutated. This led to the idea that genetic screening should sequence a larger proportion of the genome in people suspected of having this disease. Discuss the ethical reasons for and against sequencing a larger proportion of the genome for people suspected of having mitochondrial complex I deficiency.
One mutation associated with mitochondrial complex I deficiency is a base substitution. It changes the amino acid glycine into the amino acid valine in a section of an $\text{-helix}$ in a protein that is important in the formation of mitochondrial complex I. Glycine is a small amino acid with an R group of one hydrogen atom, whereas valine has a larger, branched R group. Predict how the amino acid change would affect the protein’s structure.