In last week’s WCMR science seminar, we heard from Dr Kyle Thompson who talked about his progress in studying a case of mitochondrial disease that was identified through the collaborative Lily Foundation-funded Exome Project. Read on to find out more.

Exome sequencing allows thousands of genes to be sequenced at once and identifies more mutations than previous sequencing technologies have allowed. However, this alone is not enough to confirm a genetic diagnosis. Any two individuals will have thousands of differences in their genetic code, most of which will not cause disease. The work presented demonstrates the use of tissue (muscle) samples and cell lines (skin fibroblasts) from patients to try to prove that the identified genetic changes are responsible for causing the suspected mitochondrial disease in this case.

The patient had mutations in a gene that is important for making a specific phospholipid that is crucial for mitochondrial structure and function. Through the use of GeneMatcher, an online tool to allow scientists to establish collaborations with other groups around the world that work on similar interests, two further patients with mutations in the same gene were identified. Finding additional cases that have very similar clinical symptoms with mutations in the same gene is a strong indicator that these mutations are responsible for the disease.

We have studied samples from the patients and shown functional consequences of the identified mutations. We have also modelled the disease by making the equivalent genetic changes in yeast. The yeast grow more poorly with the equivalent mutations to the patients compared to the normal gene, which is again suggestive that these mutations are causative of the mitochondrial disease.