Human Genome Project Information Archive
1990–2003

SNP Consortium Collaborates with HGP, Publishes First Progress Reports

The Human Genome Project (HGP) and The SNP Consortium (TSC, http://snp.cshl.org) announced plans to generate a new set of human DNA sequence data that will contribute 125,000 to 250,000 validated and useful DNA markers known as SNPs. The DNA to be sequenced will come from 24 anonymous, unrelated donors with diverse geographic origins, and all data will be made publicly available. Researchers expect to complete the project by December.

A high-density map of SNPs (single base-pair variations that occur about once every 100 to 300 bp throughout human DNA) is expected to be a valuable research tool. It will help scientists pinpoint genetic differences that predispose some people to disease and underlie variable individual responses to treatment.

Three genome research centers are participating in the HGP-TSC collaboration: Whitehead Institute, Washington University School of Medicine (St.Louis), and the Sanger Centre (United Kingdom). These centers will isolate at least 2.5 million DNA fragments (each about 6000 bp long) from the human genome and determine the sequence of about 500 bp at both ends of the fragments, resulting in paired-end sequences a known distance from each other. The sequences then will be compared to those already in GenBank. The paired-end data will help span some gaps in the human genome working draft, thus making the draft more accurate.

"The collaboration between the HGP and TSC demonstrates that public-private cooperation can be an efficient means for developing basic research tools essential for the application of genetic information to the understanding and treatment of diseases," noted Arthur Holden, chairman and chief executive officer of TSC.

The nonprofit TSC foundation was established by the Wellcome Trust and a group of pharmaceutical and technological companies with the initial goal of identifying and locating up to 300,000 SNPs by the end of 2001. An exponential increase in the amount of HGP data, however, has since enabled TSC to proceed at a much faster pace. By September, it had identifed more than 350,000 SNPs and mapped almost 250,000 to the working draft sequence. With the HGP collaboration, the total number of useful SNPs mapped may exceed 750,000 by December.

First TSC DNA Variation Map
The first publications on the methodology and progress of TSC appeared in the September 28 issue of Nature. Eric Lander and his team at the Whitehead Institute Center for Genome Research reported on a new method called reduced representation shotgun sequence (RSS) that increases the accuracy of SNP mapping. RSS scans subsets of markers from several people and compares the resulting sequences to identify DNA variations. In a second Nature paper, a team of TSC researchers from the Sanger Centre presented a human chromosome 22 map featuring 2730 SNPs identifed by RSS and aligned to the human genomic sequence. Most of the SNPs are within 25 kb of a transcribed exon (protein-coding region), making them useful for association studies. Chromosome 22, the second smallest of the chromosomes, is linked to more than 35 diseases and syndromes including some cancers, schizophrenia, and heart disease.

The goal of TSC is to build a map containing one SNP every 5 kb that is integrated with the human genome sequence and freely available to all researchers (600,000 SNPs evenly spaced throughout the human genomes 3 billion bases). In September, scientists reported the total number of SNPs now in the public domain to be more than 1.2million, scattered across the genome.

The ultimate aim of SNP studies is to develop customized therapies to treat or prevent disease. In the September 13 issue of Proceedings of the National Academy of Sciences, researchers moved a step closer to that goal as they reported for the first time the ability to predict an individuals response to a drug based on that persons particular group of SNP markers. The study involved asthmatic volunteers and responses to albuterol, a drug commonly used to achieve rapid improvement in lung function.

As more clinical studies get under way and advances eventually become established in clinical practice, the urgency increases to find effective ways to protect the genetic privacy of individuals. In response to these projected needs, several members of TSC formed a new company, First Genetic Trust, Inc., to act as an independent intermediary between genetic information providers (individuals) and users (researchers and healthcare providers). The company aims to protect the rights of individuals in regard to the confidentiality and access of their genetic data. The first priority of the company will be to address the needs of the pharmaceutical industry as it conducts clinical trials.

The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v11n1-2).