The Genom of Homo sapiens.pdf

50 COLLINSand expand the genomics revolution now under way innearly all realms of biological science.Build a Human Haplotype MapOne of the greatest opportunities facing biological researchersin the genome era is defining and analyzing humangenetic variation. Although humans are 99.9% geneticallyidentical, the 0.1% variation in DNA sequencesholds crucial clues to individual differences in susceptibilityto disease and response to drugs.In October 2003, a public–private research consortiumconsisting of Japan, the United Kingdom, Canada, China,and the United States launched the International HapMapProject (http://www.genome.gov/HapMap) with the goalof defining and tagging the most common blocks of geneticvariation, or haplotype blocks, that cover 80–90%of the human genome. When completed, the human haplotypemap (HapMap) will serve as a valuable tool forscientists searching for common genetic variations associatedwith complex diseases, as well as variations associatedwith differences in drug response.Initially, researchers will study DNA from 270 peoplein widely distributed geographic regions, which were selectedin an effort to find genetic variations that are commonin most populations around the globe. Samples arebeing collected from the Yorubas in Nigeria, Japanese,Han Chinese, and U.S. residents of northern and westernEuropean descent.Expected to take three years to complete, the HapMapwill reduce from 10 million to roughly 300,000 the numberof single-nucleotide polymorphisms (SNPs) requiredto examine the whole genome for association with a phenotype.This will make genome-scan approaches to findinggenes that influence disease susceptibility muchmore efficient and comprehensive, since effort will notbe wasted typing more SNPs than necessary, and all regionsof the genome can be included. Ultimately, theHapMap with its select, gold-standard set of haplotypetag SNPs is expected to enable genome-wide associationstudies to be conducted at 30–40 times less cost than iscurrently possible.In addition to speeding the hunt for genes associatedwith a wide range of complex diseases and conditions, theHapMap should prove a valuable resource for studyingthe genetic factors contributing to individual variation inresponse to drugs and vaccines, as well as those that influenceresponse to environmental factors.Sequence Additional GenomesAlthough the effort to produce a reference sequence ofthe Homo sapiens genome is essentially completed, thereremains a compelling need to sequence the genomes ofmany more species, both vertebrate and invertebrate. Theability to conduct comparative analyses of genomic sequencesof various species has provided biologists withan amazing new window into evolution and genomicfunction (Thomas et al. 2003). Given the power of comparativegenomics, there exists an immense hungeramong biologists for free and publicly available sequencedata on a wide variety of organisms, and sequencersshould feed that hunger.Develop New Technologiesfor Genomics ResearchQuantum leaps in technology must be made if our genomics-basedvision is to realize its full potential forbiomedical research. One of the most ambitious goals isthe development of technology that would allow researchersto sequence the genome of a human or othermammals for $1,000 or less—a cost at least four ordersof magnitude lower than is possible with current technology.Yet another major technological hurdle involves loweringthe cost of synthesizing DNA, with the ultimategoal being the synthesis of any DNA molecule at high accuracyfor $0.01 or less per base. This would transformmany of the ways in which biological research is carriedout, allowing researchers to efficiently “write” DNA sequencesin much the same way they can now easily“read” sequence by DNA sequencing. Researchers alsowant and should have the technological capacity to identifyand simultaneously analyze a wide array of geneticand protein elements within a single cell, including determiningthe methylation status of all DNA.Identify All Functional Elementsof the GenomeAlthough biology has proven enormously successful insequencing genomes, our experimental and computationalmethods are still primitive in identifying elementsthat are not involved in protein coding, which make upabout two-thirds of the highly conserved DNA in the humangenome. An NHGRI-led consortium made up of scientistsin government, industry, and academia recentlyset out to develop efficient ways of identifying and preciselylocating all of the functional elements contained inthe human DNA sequence. The ultimate goal of theENCyclopedia Of DNA Elements (ENCODE) project(http://www.genome.gov/ENCODE/) is to create a referencework that will help researchers mine and fully utilizethe human sequence to gain a deeper understanding of humanbiology, as well as to develop new strategies for improvinghuman health.The first phase of ENCODE will focus on developinghigh-throughput methods for rigorously analyzing a definedset of DNA target regions comprising ~30megabases, or 1%, of the human genome. This pilot projectshould lay the groundwork for a large-scale effort tocharacterize all of the protein-coding genes, non-proteincodinggenes, and other sequence-based functional elementsin the human genome. As has been the case withthe Human Genome Project, data from the ENCODE projectwill be collected and stored in a database that will befreely available to the entire scientific community.