ABSTRACT
The human genome is highly polymorphic, with substantial quantitative and qualitative variation in DNA sequence distributed across all chromosomes. While much of this variation is situated in the approximately 97 percent of genomic DNA sequence that is devoid of transcribed elements and is likely of little consequence, virtually all heritable phenotypic variation is conferred by a subset of these variants that interfere with normal gene function or regulation. The primary aim of human genetic research is to identify this functional subset of variation, and correlate genetic variants with their phenotypic outcomes. A major challenge of this research is to characterize the genetic variation in populations reliably, with high accuracy and at low cost. The advent of a comprehensive physical map of the human genome, public databases to catalog identified variants, and the development of accurate high-throughput sequencing and genotyping technologies have helped to overcome many of the obstacles, usher in the post-genomic era, and accelerate the pace of genetic research to unprecedented levels. In this chapter we outline the common forms of genetic variation implicated in health and disease, and provide a survey of the contemporary technologies available for identifying and genotyping genetic variation. Due to the rapid pace of technological advancement and the virtually continuous announcement of new technologies and applications, we are unable to provide a comprehensive review of all available platforms. Rather, we hope to describe the current state-of-the-art in molecular genetic technologies, with the aim to introduce the reader to the fundamental concepts of this research.
