1. Genome architecture and sequence variation in health and disease

Availability of information on DNA sequence in human genomes and advances in technologies to amplify and sequence DNA have led to significant progress in delineating sequence differences that lead to disease. These techniques have also led to the discovery of sequence variants that occur in healthy individuals.

Studies of variation in the human genome are greatly facilitated through the availability of microarrays designed to detect single nucleotide polymorphisms (SNPs) that occur with frequencies greater than 1% to 5% in the population. Gene loci that are close to each other are often coinherited. SNP analyses can determine a series of alleles of loci in a specific region (a haplotype). Microarray technologies enable analysis of as many as one million SNPs on each array. These microarrays can also determine structural variation and copy number changes, defined as deletion or duplications greater than 1 kilobase (kb). Specific probes for regions known to frequently harbor copy number changes are also present on SNP microarrays such as the Affyme....