Basic principles and laboratory analysis of genetic variation

With the draft of the human genome and advances in technology, the approach toward mapping complex diseases and traits has changed. Human genetics has evolved into the study of the genome as a complex structure harbouring clues for multifaceted disease risk with the majority still unknown. The discovery of new candidate regions by genome-wide association studies (GWAS) has changed strategies for the study of genetic predisposition. More genome-wide, "agnostic" approaches, with increasing numbers of participants from high-quality epidemiological studies are for the first time replicating results in different settings. However, new-found regions (which become the new candidate "genes") require extensive follow-up and investigation of their functional significance. Understanding the true effect of genetic variability on the risk of complex diseases is paramount. The importance of designing high-quality studies to assess environmental contributions, as well as the interactions between genes and exposures, cannot be stressed enough. This chapter will address the basic issues of genetic variation, including population genetics, as well as analytical platforms and tools needed to investigate the contribution of genetics to human diseases and traits.