Genetic Asthma and the Human Genome Project
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Genetic Asthma and the Human Genome Project
By Michael P. Hahn, RRT
Caregivers have known for years that asthma runs in certain families. This tendency became apparent after a study showed identical twins with the same genes and same genetic traits, including identical appearance, acquired the same diseases and disorders.
In contrast, dizygotic twins inherit only about 50 percent of the same genes and, therefore, may not develop the same diseases.
People are not born with asthma. Rather, they inherit asthma genetic codes that make them susceptible to acquiring asthma once they encounter specific environmental triggers. As long as the triggers are avoided, the individual will not become asthmatic.
Although approximately 1,500 inherited diseases (including cystic fibrosis and sickle cell anemia) are caused by a single gene, asthma is one of many complex genetic disorders with a pathogenesis linked by a number of contributing genes. In other words, asthma is not just some sudden muscle spasm in the bronchiole tubes; it usually consists of the migration of inflammatory mediator cells into the airway, with a resulting combination of mucosal swelling, congestion, and increased bronchomotor tone.
SINGLE GENE PHENOTYPES
There have been a lot of advancements in genetic research during the past two decades. During the 1980s, scientists identified the phenotype responsible for causing many of the single-gene diseases like cystic fibrosis. Despite such advancements, there has been little difference in the therapeutic management of these single-gene diseases.
Additionally, the ability to use genetic markers to help predict which individuals are susceptible to attaining asthma currently remains no better a method of finding something like asthma than is the older method of simply asking individuals whether they have a family history of asthma.
ASTHMA LINKAGE STUDIES
Some of the specific areas of allergy and asthma genetic linkage research currently being investigated include the following areas: Chromosome 5 (including interleukin-3, -4, -5, -9, and 13; chromosome 11, chromosome 16 [the IL-4 receptor], and chromosome 12 (stem cell factor, nitric oxide synthetase, insulin growth factor, and Stat 6 [IL-4 stat] ). There are also disease-contributing alleles for the beta-adrenergic receptor, 5-lipoxygenase, and leukotriene C4 synthase.
Environmental risk factors that can contribute to the pathogenesis of the asthma phenotype include smoking and second-hand smoke exposure, maternal smoking, certain dietary constituents and viral respiratory infections.
HUMAN GENOME PROJECT
In 1990, a publicly funded international Human Genome Project got under way to identify the nearly 100,000 genes in the human body. In the United States, the project is being conducted by the National Institutes of Health’s National Human Genome Research Institute and the Department of Energy’s Human Genome Program.
The human genome is the blueprint for making a human being, including the lifetime instructions for all cellular activities, and for making all cellular structures, including proteins, enzymes and chemicals. The human genome consists of tightly coiled threads of deoxyribonucleic acid (DNA) and associated protein molecules, organized into structures called chromosomes.
If unwound and tied together, the double helix strands of DNA found in the trillions of cells in a human body would stretch more than 5 feet in length but would be only 50 trillionths of an inch wide.
Four different nucleotide bases are found in human DNA: Adenine (A), thymine (T), cytosine (C), and guanine (G). With these four letters there are 64 triple-letter combinations possible. The bases are the rungs in a DNA ladder, and three bases are called codons. The codons transcribe which one of 20 different amino acids is to be added to help construct a protein molecule (polypeptide chain). For example, the base sequence ATG (adenine + thymine + guanine) is the amino acid methionine.
The human body can synthesize nearly 100,000 different kinds of proteins. The first codon is called an initiation codon and indicates the beginning of a polypeptide chain to construct a protein. The final codon is the termination codon and indicates the manufacture of the protein is completed. Any genetic disorder is essentially one or more codons that do not have the appropriate sequence in its DNA ladder.
While most genetic diseases are inherited from parents, they can also be acquired through excessive exposure to radiation or some other toxic substance.
The initial goal of the Human Genome Project was to compile all of the human genome information by 2005. The project ran ahead of schedule, spurred on by a private firm heavily focused on the study, and amidst great fanfare, the completion of the rough draft (97 percent) was announced late last month in a joint announcement by Celera Geonomics Inc. and the Human Genome Project.
Celera is a private U.S. enterprise headquartered in Rockville, Md. Both groups will be publishing details of their work sometime this fall. The final human genome data will be released on a compact disk and is expected to occupy 3 gigabytes of space or (3 billion bytes).
That will occupy less space than a printed form. A hard copy of the human genome data is expected to equal 200 volumes of 1,000 pages apiece. It would take 9.5 years of constant reading to get through all 3 billion bases in the human genome.
By mapping the human genome, genetic investigators will be able to discover better treatments and cures for diseases and better understand disease pathophysiology leading to specific measures to help people avoid acquiring diseases.
There is also the possibility of using the genome data to create designer babies or tests to assess insurance premiums or to help select good employees. But these are still years away. *
Hall IP. Genetics and Pulmonary Medicine: Asthma. Thorax (1999;54:65-69).
Wiesch DG, Meyers DA, Bleecker ER. Genetics of Asthma. J Allergy Clin Immunol (1999;104:895-901).
Michael Hahn, a California practitioner, can be reached at [email protected].