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Gene Mapping Essay, Research Paper

Gene Mapping began when the U.S. Government held a conference to explore if DNA damage occurred in people exposed to low levels of radiation in Japan after the 1945 Atomic Bombs. There, scientists quickly realized that observing the human genome could be useful in discovering environmental mutates. Shortly afterwards, Renato Dulbecco revealed the entire sequence of human DNA and had a great impact on cancer research (Purves, et al. 1998).

In 1990, scientists from around the world began the Human Genome Project and would set out to map the human genome to provide a key to the collective history of human disease that will allow an unprecedented acceleration of the study of pathogenesis. The first stage of the project was the construction of a genetic linkage map followed by a variety of physical maps (see illustration one).

The Human Genome Project (HGP) is a federally funded research project that was expected to take 15 years from the start and cost several billion dollars. The project was controversial from the start over its scientific worth relative to other projects and had considered the private sector for financing the HGP (Annas and Elias, 1992).

With the overall intent of furthering the basic scientific understanding of human genetics and the role of genes in health and disease, the project’s initial goals were:

+ Construction of a high-resolution genetic map of the human genome.

+ Production of a variety of physical maps of all human chromosomes and of the DNA of selected model organisms with emphasis on maps that make the DNA accessible to investigators for further analysis. The series of maps would be of increasing fine resolution.

+ Determination of the complete sequence of human DNA and DNA of selected model organisms (Annas and Elias, 1992).

In fact, with the development of new technology, faster, more accurate and less expensive methods of mapping have developed. Speculating that it may be finished before its target date of 2005 (Murray, et al. 1996).

The Human Genome project was to gain a basic understanding of the entire genetic blueprint of a human being. This genetic information is found in each cell of the body, encoded in the chemical deoxyribonucleic acid (DNA). The project is intended to identify all the genes in the nucleus of a human cell, to establish, by a process known as mapping where those genes are located on the chromosomes in the nucleus (see illustration two). Then, determine by a progress known as sequencing the genetic information encoded by the order of the DNA’s chemical sub units (Murray, et al. 1996).

DNA typically comes from small samples of blood or tissue obtained from many different people. Although the genes in each person’s genome are made up of unique DNA sequences, the average variation in the genomes of two different people is less than one percent. DNA fingerprints are derived from traces of human biological material such as blood, semen, hair, or other tissue. This DNA technology is applied to samples to identify patterns of genetic sequences that are unique of each human being. Matched DNA fingerprints can establish the identity of a given person with near certainty. Therefore, DNA technology has given the practical use of identifying criminals, family members, and bodily remains (Gibbons, 1998).

Currently, the HPG is ahead of schedule and under budget. More than 4800 genes have been mapped at least to a specific chromosome, 2900 genes of known functions have been cloned, 1000 genetic diseases have been associated with a defect in a mapped gene, and more than 35 million base pairs of unique human DNA had been sequenced. Maps of the entire human genome have been published, with an average of 110,000 base pairs apart. The ultimate goal is to sequence all 3 billion base pairs by the year 2005 (Murray, et al. 1996).

There are two main categories of gene mapping, linkage and physical. The linkage mapping method identifies only the relative order of genes along a chromosome. Physical mapping can place genes at specific distances from one another on a chromosome. Both types of mapping use genetic markers, detecting physical or molecular characteristics that differ among individuals and that are passed from one generation to the next (Shook, et al. 1991). The linkage of genetic maps describes the positions of genes on chromosomes relative to one another by determining how frequently two marks are inherited together (see illustration three). Based on the principle that any two markers or genes that are positioned closely together are more likely to be inherited together when reshuffling of chromosomal DNA occurs during Meiosis, genetic maps describe the distance between markers in centimorgans. Two markers are said to be one centimorgan apart if they are separated during recombination 1% of the time. This unit of measure, while highly variable, is approximately 1,000,000 base pairs. Markers must be polymorphic, existing in more than one form (Schook, et al. 1991).

Now virtually all polymorphic markers useful for mapping are variations in DNA sequences; those found on exons, which are portions of a DNA molecule that codes part of a polypeptide, are potentially associated with visible differences among individuals such as eye color. While those found on introns, which are portions of a DNA molecule that is not involved in coding parts of polypeptide molecules, usually have little effect on the organism but are detectable at the DNA level and can be utilized as markers. In 1994 the first comprehensive report was published including nearly 6,000 markers spaced an average of less than 1 million base pairs apart (Schook, et al. 1991). The most important part of physical mapping of the chromosome is the single continuous molecule of DNA. This double stranded molecule, shaped like a twisted

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