Last Chromosome Mapped

August 1, 2006

A team of British and American scientists has completed the detailed genetic mapping of human chromosome 1, the largest single unit of genetic material in the human genome and the final chromosome to be completely sequenced.

Researchers at the Wellcome Trust Sanger Institute and Duke Medical Center led the effort, which involved more than 150 scientists and took about ten years to complete. Their findings were published in the journal Nature.

"This achievement effectively closes the book on an important volume of the Human Genome Project, which was started in 1990 to identify the genes and DNA sequences that provide a 'blueprint' for human beings," says Simon G. Gregory, assistant professor at the Duke Center for Human Genetics and lead investigator on the study.

"Armed with this new information, researchers now have new tools for probing fundamental biological questions and examining the genetic factors involved in a range of diseases and medical conditions, including Alzheimer's disease, Parkinson's disease, cancer, autism, and mental retardation," Gregory says.

The twenty-three human chromosomes are made up of millions of chemical subunits called bases. The chromosomes are numbered from largest to smallest. Chromosome 1 makes up about 8 percent of the overall human genome and contains about twice as many genes as an average-sized chromosome.

In their study, the researchers determined that chromosome 1 contains 3,141 genes, roughly a thousand of which had never before been identified. Before coming to Duke in 2003, Gregory led the chromosome 1 project at the Wellcome Trust Sanger Institute, which has sequenced more of the human genome than any other institution.

Chromosome 1 plays a critical role in human health and well-being, he says. Scientists have linked genetic mutations of the chromosome to more than 350 human diseases, and structural alterations of the chromosome are believed to contribute to a variety of mental-retardation syndromes.

Gregory's colleagues at Duke have already used information from the chromosome 1 sequence to identify genes associated with certain forms of Charcot-Marie-Tooth disease, a neurological disorder that causes loss of sensation to parts of the body.

In addition to mapping the chromosome's genes, the U.S.-U.K. team identified almost 4,500 new single nucleotide polymorphisms (SNPs), sections of DNA that vary slightly from the standard sequence. In previous work, scientists identified fifteen SNPs that influence the risk of developing diseases, including malaria. However, the functions of the newly identified SNPs have yet to be determined.

The new genetic map of chromosome 1, Gregory says, will also help scientists better understand the processes that contribute to genetic diversity among human populations.