The Human Genome Project was an international research effort to determine the sequence of the human genome and identify the genes that it contains. After the idea was picked up in 1984 by the US government when the planning started, the project formally began in 1990 and was completed in 2003, 2 years ahead of its original schedule. The Project was coordinated by the National Institutes of Health and the U.S. Department of Energy. Additional contributors included universities across the United States and international partners in the United Kingdom, France, Germany, Japan, and China.
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The main goals of the Human Genome Project were to provide a complete and accurate sequence of the 3 billion DNA base pairs that make up the human genome and to find all of the estimated 20,000 to 25,000 human genes. The sequence would act as a template for the annotation of genes discovered in the future: if a geneticist found a novel gene that increases the risk for breast cancer, for instance, she should be able to decipher its precise location and sequence by mapping it to the master sequence of the human genome. By comparing abnormal genes to the normal genes in the template, the geneticist would be able to map the mutation responsible for causing the disease.
The potential benefit of a comprehensive sequencing effort was highlighted by the isolation of disease-linked genes such as Huntington’s disease, Cystic Fibrosis, and the most common breast-cancer-associated gene, BRCA1. The one-gene-at-a-time approach was very inefficient and laborious. It only worked for “monogenic” diseases. But most common human diseases are genomic – “polygenic” diseases caused by multiple genes spread diffusely throughout the human genome. Cancer and mental illnesses are examples of genomic diseases.
Public versus Private Approaches
In 1998, a similar, privately funded quest was launched by the American researcher Craig Venter, and his firm Celera Genomics. Venter was a scientist at the NIH during the early 1990s when the project was initiated. The $300,000,000 Celera effort was intended to proceed at a faster pace and at a fraction of the cost of the roughly $3 billion publicly funded project.
Celera used a technique called whole genome shotgun sequencing, employing pairwise end sequencing, which had been used to sequence bacterial genomes of up to six million base pairs in length, but not for anything nearly as large as the three billion base pair human genome.
Celera initially announced that it would seek patent protection on “only 200-300” genes, but later amended this to seeking “intellectual property protection” on “fully-characterized important structures” amounting to 100-300 targets. The firm eventually filed preliminary (“place-holder”) patent applications on 6,500 whole or partial genes. Celera also promised to publish their findings in accordance with the terms of the 1996 “Bermuda Statement”, by releasing new data annually (the HGP released its new data daily), although, unlike the publicly funded project, they would not permit free redistribution or scientific use of the data. Ultimately, Celera afreed to provide free access to academic researchers – but with several important constraints.
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Although a working draft was announced on June 26, 2000 (jointly by U.S. President Bill Clinton and the British Prime Minister Tony Blair), it was not until February 2001 that Celera and the HGP scientists published details of their drafts. These drafts covered about 83% of the genome (90% of the euchromatic regions with 150,000 gaps and the order and orientation of many segments not yet established). In February 2001, at the time of the joint publications, press releases announced that the project had been completed by both groups. Improved drafts were announced in 2003 and 2005, filling in to approximately 92% of the sequence currently.
The Book of Man
- It has 3,088,286,401 letters of DNA
- It is divided into twenty-three pairs of chromosomes. All other apes have twenty-four pairs.
- It encodes about 20,687 genes in total – only 1,796 more than worms, and 12,000 fewer than corn.
- It is fiercely inventive. Gene regulation and gene splicing are used more extensively in the human genome than in the genome of other organisms. It squeezes complexity out of simplicity, produces near-infinite functional variations out of its limited repertoire.
- It is dynamic. In some cells, it reshuffles its own sequence to make novel variant of itself.
- Parts of it are surprisingly beautiful.
- An enormous proportion (about 98%) is not dedicated to genes per se, but to enormous stretches of DNA that are interspersed between genes (intergenic DNA) or within genes (introns). These stretches encode no RNA, and no protein.
- It is encrusted with history.
- It has repeated elements that appear frequently.
- It has enormous “gene family” – genes that resemble each other and perform similar functions – which often cluster together.
- It contains thousands of “pseudogenes” – genes that were once functional but ahve become nonfunctional, ie, they give rise to no protein or RNA.
- It accommodates enough variation to make each one of us distinct, but enough consistency to make each of us different from other species.
- Its first gene, on chromosome one, encodes a protein that senses smell in the nose. Its last gene, on chromosome X, encodes a protein that modulates the interaction between cells of the immune system.
- The ends of its chromosomes are marked with “telomeres.” Like the little bits of plastic at the ends of shoelaces, these sequences of DNA are designed to protect the chromosomes from fraying and degenerating.
- Although we fully understand the genetic code – ie how the information in a single gene is used to build protein – we comprehend virtually nothing of the genomic code – ie, how multiple genes spead across the human genome coordinaet gene expression in space and time to build, maintain, and repair a human organism
- It imprints and erases chemical marks on itself in response to alterations in its environment – thereby encoding a form of cellular “memory.”
It is poised to evolute. It is littered with the debris of its past.
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