Grant: Operating Grant

Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motor neurons in the central nervous system and given that efficient treatments are sorely missing the disease typically follows its course toward the patients' death, a few years after onset. While the discovery of several genes has led to significant new insights into the cause of ALS both the basic pathogenic mechanism and the genetic basis of most cases remain unknown. Therefore, it is still necessary in 2009 to identify additional ALS-causing genes. To accomplish this, we will use the more recent and powerful generation of DNA sequencing technologies to resequence the entire coding genome "all the coding genes", or "exome", in a collection of 60 familial ALS patients (and unaffected relatives) that were selected (14-17 families) from our biggest and best clinically characterized families segregating ALS. This will enable us to identify novel potentially causative ALS genes. Any genes shown to underlie familial ALS will subsequently be screened in additional familial and sporadic ALS cases to confirm and establish their genuine implication. Overall, this will have a significant impact on our understanding of all ALS pathogenic mechanisms.