Whole Genome Resequencing and 1000 Genomes Project

Abstract The recent advances in sequencing technologies have enabled the whole human genome to be sequenced within weeks. To date, several human diploid genomes have been sequenced and the number of genomes being sequenced is expected to increase in the years to come. In fact, a 3‐year international collaborative project, the 1000 Genomes Project, was initiated in 2008 to sequence at least 1000 individual genomes from different populations around the world. The aim is to create the most detailed and comprehensive map of genetic variations in the human genome for future disease‐association studies and biomedical research. While waiting for this ambitious project to be completed, several whole genome sequencing studies have already provided some exciting results, where hundreds of thousands of new SNPs and short indels have been identified. In addition, these studies also address many important questions and issues in the experimental design and data analysis of whole genome sequencing. Key concepts: The arrival of next generation sequencing (NGS) and third generation sequencing technologies has empowered the sequencing of the whole human genome to be completed within weeks. The first human whole genome sequencing (WGS) study using a next generation sequencer was completed in 2008, which marked the beginning of a new era in personalized genome sequencing. To date, several WGS studies have been done using NGS technologies. The NGS technologies are Roche ® 454 Life Science Genome Sequencer FLX (GS FLX), Illumina ® Genome Analyzer (GA) and Applied Biosystems ® (ABI) Supported Oligonucleotide Ligation Detection System (SOLiD). The WGS studies have clearly demonstrated the feasibility of using all the NGS and third generation sequencing technologies to decode the DNA sequence of human genome efficiently and at an affordable price per genome. In addition, these studies have also addressed many important questions and issues surrounding the experimental design and data analysis in whole genome sequencing. The more significant finding from the WGS studies is that they have conclusively revealed the richness of genetic variations in the human genome. The genetic variations in the human genome are more abundant than previously expected. Several thousands of structural variations are found in all the WGS studies, and the studies also identified hundreds of thousands of indels. Personalized genome sequencing is able to provide full DNA sequences and identify the enormous number of genetic variations in the genome. However, personalized medicine aims to predict individual susceptibility risks to various diseases and responses to drug therapies using the genetic variation information. To achieve personalized medicine, the first steps are to detect and validate all the genetic variations in the human genome in population‐based studies, and catalogue them properly in databases, so they can be used as the genetic markers for future disease association studies.