**1. Introduction**

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness caused by loss of central and peripheral motor neurons. Symptoms typically have a localized limb or bulbar onset and progress to other muscle groups of the body. Denervation of respiratory muscles and dysphagia leading to respiratory complications are the most common causes of death. There is no cure for this rapidly progressive disease.

Approximately 5% of patients have a family history of ALS (fALS) (Byrne et al., 2011). All other cases are considered to have a sporadic form of the disease (sALS). A twin study of sALS patients has estimated hereditability to be considerable (0.38-0.76), indicating an important genetic component in disease etiology (Al-Chalabi et al., 2010). sALS, therefore, is considered to be a disease of complex etiology with both genetic and environmental factors contributing to disease susceptibility.

This chapter will provide an overview of the current knowledge of the genetics of both fALS and sALS. There will be, however, particular emphasis on two sALS associated regions identified in a large genome wide association study namely, chromosomal region 9p21.2 and 19p13.11. Evidence for the association with these regions as well as the function of the relevant genes in these regions will be discussed.
