Human Genome Project

The Human Genome Project is the scientific research effort to construct a complete map of all of the genes carried in human chromosomes. The finished blueprint of human genetic information will serve as a basic reference for research in human biology and will provide insights into the genetic basis of human disease.

The human "genome" is the word used to describe the complete collection of genes found in a single set of human chromosomes. It was in the early 1980s that medical and technical advances first suggested to biologists that a project was possible that would locate, identify, and find out what each of the 100,000 or so genes that make up the human body actually do. After investigations by two United States government agencies—the Department of Energy and the National Institutes of Health—the U. S. Congress voted to support a fifteen-year project, and on October 1, 1990, the Human Genome Project officially began. It was to be coordinated with the existing related programs in several other countries. The project's official goals are to identify each of the more than 100,000 genes in human deoxyribonucleic acid (DNA) and to determine the sequences of the 3,000,000,000 base pairs that make up human DNA. The project will also store this information in databases, develop tools for data analysis, and address any ethical, legal, and social issues that may arise.

In order to understand how mammoth an undertaking this ambitious project is, it is necessary to know how genetic instructions are carried on the human chromosome. Humans have forty-six chromosomes, which are coiled structures in the nucleus of a cell that carry DNA. DNA is the genetic material that contains the code for all living things, and it consists of two long chains or strands joined together by chemicals called bases, or nucleotides, all of which is coiled together into a twisted-ladder shape called a double helix. The bases are considered to be the "rungs" of the twisted ladder. These rungs are made up of only four different types of submolecules called nucleotides—adenine (A), thymine (T), guanine (G), and cytosine (C)—and are critical to understanding how nature stores and uses a genetic code. The four bases always form a "rung" in pairs, and they always pair up the same way. Scientists know that A always pairs with T, and G always pairs with C. Therefore, each DNA base is like a letter of the alphabet, and a sequence, or chain of, bases can be thought of as forming a certain message.

The human genome, which is the entire collection of genes found in a single set of chromosomes (or all the DNA in an organism), consists of 3,000,000,000 nucleotide pairs or bases. To get some idea about how much information is packed into a very tiny space, a single large gene may consist of tens of thousands of nucleotides or bases, and a single chromosome may contain as many as 100,000,000 nucleotide base pairs and 4,000 genes. What is most important about these pairs of bases is the particular order of the A's, T's, G's, and C's. Their order dictates whether an organism is a human being, a bumblebee, or an apple. Another way of looking at the size of the human genome present in each of our cells is to consider the following phone book analogy. If the DNA sequence of the human genome were compiled in books, 200 volumes the size of the Manhattan telephone book (1,000 pages) would be needed to hold it all. This would take 9.5 years to read aloud without stopping. In actuality, since the human genome is 3,000,000,000 base pairs long, it will take 3 gigabytes of computer data storage to hold it all.

FRANCIS SELLERS COLLINS

American geneticist Francis Collins (1950– ) became the director of the National Human Genome Research Institute in 1993. The goal of this international scientific research effort is to construct a complete map of all of the genes (the units of heredity) carried on human chromosomes (a coiled structure in the nucleus of a cell that carries the cell's deoxyribonucleic acid). This finished blueprint of human genetic information will then serve as a basic reference for research in human biology and will provide insights into the genetic basis of human disease. Collins's own research is in the identification and understanding of genes that cause disease.

Francis Collins was raised on a small farm in Staunton, Virginia, where he was home-schooled until the sixth grade. After obtaining his bachelor's degree from the University of Virginia in 1970, he went on to obtain a doctorate in physical chemistry from Yale University in 1974. At this point, he became so intrigued by what he saw as the beginnings of a revolution in molecular biology (the study of the complex chemical molecules in all living things), that he switched fields and went back to school. After enrolling in medical school at the University of North Carolina, he began to study medical genetics and knew he was finally doing what he really wanted. After obtaining his medical degree in 1977, he returned to Yale for a fellowship in human genetics. It was there that he began working on the problem of trying to identify genes in human deoxyribonucleic acid (DNA) that cause disease. He continued studying this problem after joining the faculty at the University of Michigan in 1984 where he developed an approach that is now called positional cloning.

Collins's approach was a major breakthrough in human genetic research as it allowed him to identify "disease genes" for almost any condition without knowing ahead of time what the particular abnormality might be. This approach has been adopted as a standard method of modern molecular genetics, and Collins demonstrated its usefulness in 1989 when his research team identified the gene for cystic fibrosis. The following year it did the same for the disease known as neurofibromatosis. This inherited disease causes tumors to form and destroys bones. In 1993 the gene for Huntington's disease was also located. That same year, Collins succeeded American biochemist James Dewey Watson (1928– ), and became the second director of the National Center for Human Genome Research at the National Institutes of Health (NIH), heading the American part of an international project that involves at least eighteen countries. Collins also founded a new research program in genome research at NIH, and his own laboratory continued to focus on the identification and understanding of the genes that cause disease. Scheduled to be completed in 2003, the Human Genome Project is regarded by many as the most important scientific undertaking of our time, and Collins is bringing it to conclusion ahead of schedule and under budget. By the year 2000, the project had already compiled what might be called a rough draft of the human genome, having put together a sequence of about 90 percent of the total.

In light of the project's main goal—to map the location of all the genes on every chromosome and to determine the exact sequence of nucleotides of the entire genome—two types of maps are being made. One of these is a physical map that measures the distance between two genes in terms of nucleotides. A very detailed physical map is needed before real sequencing can be done. Sequencing is the precise order of the nucleotides. The other map type is called a genetic linkage map and it measures the distance between two genes in terms of how frequently the genes are inherited together. This is important since the closer genes are to each other on a chromosome, the more likely they are to be inherited together.

As an international project involving at least eighteen countries, the Human Genome Project was able to make unexpected progress in its early years, and it revised its schedule in 1993 and again in 1998. Completion is expected in 2003, coinciding with the fiftieth anniversary of Watson and Crick's description of the molecular structure of DNA. During December 1999, an international team announced it had achieved a scientific milestone by compiling the entire code of an complete human chromosome for the first time. Another achievement was made in June 2000, when researchers announced that they had completed what might be called a rough draft of the human genome, having put together a sequence of about 90 percent of the total. Researchers chose chromosome twenty-two because of its relatively small size and its link to many major diseases. The sequence they compiled is over 23,000,000 letters in length and is the longest continuous stretch of DNA ever deciphered and assembled. What was described as the "text" of one chapter of the twenty-three-volume human genetic instruction book has been completed. Francis Collins, Director of the National Human Genome Research Institute of the National Institutes of Health said, "To see the entire sequence of a human chromosome for the first time is like seeing an ocean liner emerge out of the fog, when all you've ever seen before were rowboats." Another major advance on the project was made in June 2000 when researchers announced that they had completed a rough draft of the fully mapped human genome.

With this fully mapped genome, biologists can for the first time stand back and look at each chromosome as well as the entire human blueprint. They will start to understand how a chromosome is organized, where the genes are located, how they express themselves, how they are duplicated and inherited, and how disease-causing mutations occur. This could lead to the development of new therapies for diseases thought to be incurable as well as to new ways of manipulating DNA. It also could lead to testing people for "undesirable" genes. However, such a statement leads to all sorts of potential dangers involving ethical and legal matters. Fortunately, such issues have been considered from the beginning, and part of the project's goal is to address these difficult issues of privacy and responsibility, and to use the completely mapped and fully sequenced genome to everyone's benefit.

[See alsoChromosomes; Genes ]