The Human Genome Project

Continuing analysis of the results includes mapping tire specific variations between the DNA of different people. Variations called single-nucleotide 

Nucieotides are defined in Section 19.7. For now think of them as the units that compose genes. 

The Human Genome Project was possible because of decades of research in biochemistry, the study of the chemical substances and processes that occur in plants, animals, and microorganisms. In this chapter, we examine the chemical substances that make life possible and some of the new technology that has resulted from this understanding. 

The completion of the Human Genome Project has set the stage for the discovery of new ways to diagnose and treat diseases, and new ways to predict who will develop a particular disease. But this will require not only a file with the bases all in a row, but an understanding of how the genes are organized within that sequence and how the genes that make proteins are read. 

Two types of DNA viruses have also been used in human gene therapy trials. Adenoviruses, double-stranded DNA viruses, can efficiently carry a larger gene into cells even if they are not dividing, but the genetic information does not become inserted into the cell s genetic material and the information may rapidly be lost. Adeno-associated virus vectors, made from small single-stranded 

DNA alone, or trapped inside a small fatty balloon that will melt into the cell s outer membrane, is also a possible vector. These vectors can carry large payloads, but because they do not include the viral genetic information, they are not very good at actually delivering the genetic material. 

All the cells in the human body contain a complete copy of the approximately 3 billion DNA base pairs that make up the human genome. With its four-letter code, DNA contains all the information needed to build the entire human body Among the first genomes to be mapped were that of the chimpanzee, mouse, rat, pufferfish, fruit fly, roundworm, bakers yeast, and the bacterium Escherichia coli. As of 2008, the genomes of some 100 species genomes are completely known. 

The DNA sequence used by the Human Genome Project was not that of a single person, but a composite from several individuals thus it is a representative human sequence. During the project, the identity of the DNA donors was kept anonymous. More blood samples were collected from volunteers than were actually used, and no names were attached to the samples that were analyzed. Thus, not even the donors knew whether their DNA samples were actually used. 

To produce a genetic map, scientists collect blood or tissue samples from family members who have a certain disease. Using various laboratory techniques, they isolate DNA from these samples and examine the pattern of bases seen only in the family members who have the disease. In this way, they can identify the defective gene that causes the disease. 

Genetic maps have been used successfully to find the single gene responsible for rare inherited diseases such as cystic fibrosis and muscular dystrophy. Maps are now being used by scientists to 

DNA sequencing simply means figuring out the exact order of the bases in a strand of DNA. In the Human Genome Project, this means the exact order of the 3 billion chemical building blocks that make up the DNA of the human chromosomes. Because the bases pair specifically, biochemists only need to identify the bases in one strand of the double-stranded DNA molecule. 

A complete human genome, the total genetic information in a haploid set of chromosomes, contains approximately 3.1 billion bases and 50,000-1000,000 genes that encode proteins. The Human Genome Project was established 

Any two human genomes are approximately 99.9% identical in sequence. Of course, the 0.1% represents a difference of 3 million bases between any two individuals, and these base differences may have profound effects on disease susceptibility, behavior, intelligence, personality, and other traits. Approximately 75% of all human genes have the same DNA sequence in all individuals except for those with rare mutations. 

The type of genetic markers employed in the dissection of the human genome include 

Restriction sites sequences of DNA digested by restriction enzymes  

Variable-number tandem repeats (VNTRs) sequences of bases that are repeated in tandem almost without change up to 40 copies  

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SK Burley, SC Almo, JB Bonano, M Capel, MR Chance, T Gaasterland, D Lm, A Sail, EW Studier, S Swammathan. Structural genomics Beyond the human genome project. Nat Genet 23 151-157, 1999. 

The Human Genome Project is also vital to medicine. A number of human diseases have been traced to genetic defects, whose positions within the human genome have been identified. Among these are... 

From the human genome project it is known, that roughly 30,000 proteins exist in humans. Currently only the 3D-structures of few thousand human pr oteins or protein domains are known. Structures of membrane-bound proteins are several magnitudes rarer. Beside efforts to solve further structures like structural genomics, there is a challenge for computational approaches to predict structures and function for homologous proteins. 

CYP2J2 is abundant in cardiovascular tissue and active in the metabolism of arachidonic acid to eicosanoids that possess potent anti-inflammatory, vaso-dilatory, and fibrinolytic properties. Polymorphic alleles with reduced function are known. Some other CYP2 subfamilies and isozymes listed in Table 1 are still not well characterized, in part because most of them were discovered in the course of the human genome project. 

The need to develop new materials for electrophoretic analysis and macromolecular separations prompted by the needs of the human genome project and the rapidly advancing fields associated with biotechnology, advances in the development of new analytical instrumentation—especially capillary electrophoresis, and practical limitations of the media currently used for gel electrophoresis [73]... 

The aims of this chapter are to briefly summarize the major findings of the Human Genome Project (HGP) and indicate their implications for biology and medicine. 

Information flowing from the Human Genome Project is having major influences in fields such as proteomics, bioinformatics, biotechnology, and pharmacogenomics as well as all areas of biology and medicine. 

Collins FS, McKusick VA Implications of the Human Genome Project for medical science. JAMA 2001 285 540. (The Feb-ruaiy 7, 2001, issue describes opportunities for medical research in the 21st century. Many articles of interest.)... 

McKusick VA The anatomy of the human genome a neo-Vesalian basis for medicine in the 21st century. JAMA 2001 286 2289. (The November 14, 2001, issue contains a number of other excellent articles—eg, on clinical proteomics, pharmacogenomics—relating to the Human Genome Project and its impact on medicine.)... 

Extensive information about the Human Genome Project.) National Institutes of Health (NIH) http //www.nih.gov/... 

A new and final chapter on The Human Genome Project (HGP) has been added, which builds on the material covered in Ghapters 35 through 40. Because of the impact of the results of the HGP on the future of biology and medicine, it appeared appropriate to conclude the text with a summary of its major findings and their impfica-tions for future work. 

Section VI consists of discussions of eleven special topics nutrition, digestion, and absorption vitamins and minerals intracellular traffic and sorting of proteins glycoproteins the extracellular matrix muscle and the cy-toskeleton plasma proteins and immunoglobulins hemostasis and thrombosis red and white blood cells the metabolism of xenobiotics and the Human Genome Project. 

The Physiome Project sets a vision that will be much harder to accomplish than that of the Human Genome Project - formally begun in October... 

The promise of being able to predict and modify the genetic characteristics of an organism fuelled massive efforts to determine the base sequences of human genes. The human genome project has now reached the goal of sequencing all the important DNA carried by humans. 

It is now almost 50 years since the structure of DNA was elucidated by Watson and Crick (1) (Fig. 1). Since then the double helix has become an icon for modern scientific achievement. With the rapid growth of molecular biology and the consequent success of the human genome project (2) we are now firmly in a post-genomic era. However, in spite of, or perhaps because of this, efforts to understand fundamental aspects of metal-ion interactions with DNA continue to be vigorously pursued. 

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