Delving deep into the ALS genome to reveal somatic mosaicism

Somatic mutations are gene defects that occur post-fertilisation throughout an individual’s life. These mutations result in some cells in the human body (for example, brain cells) having a slightly different DNA code compared to other cells in the body (for example, blood). Detrimental gene defects in the brain, that we cannot detect in blood, may be leading to neurodegeneration in sporadic MND patients. Typically, blood DNA has been used to find gene defects in MND patients since it is readily available and affordable to sequence. However, gene defects unique to the brain cannot be examined in blood DNA. Here we propose to use deep genome sequencing of sporadic MND patient blood DNA and brain DNA to uncover brain-specific gene defects, and to determine whether they can be detected in cerebrospinal fluid.