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| The Genetics of Asthma, a Complex Disease |
Asthma, which can be considered a consequence of an overly sensitive immune system, is a substantial and growing health problem. As of the year 2000 it was the eighth-most prevalent chronic disease in the United States and affected about fifteen million Americans. That's an increase of more than fifty percent between 1982 and 1996. While this dramatic increase underscores a clear environmental component to asthma, asthma is also a genetic disease. The likelihood for getting asthma varies widely and has been known to run in families. Identical (monozygous) twins have a higher concordance of their asthma susceptibility than do fraternal (dizygous) twins.
The genetics of asthma, like the genetics of most prevalent diseases, is complex. There is no single gene for asthma, coronary heart disease, or most forms of cancer. Moreover, the severity of asthma-related symptoms follows a continuum. During the 1990s geneticists have been increasingly able to map complex, continuous conditions to regions of the genome. About a dozen different regions of the genome have been identified for having effects on asthma susceptibility. Interestingly, asthma propensity maps to different genetic regions depending on which ethnic group(s) are studied. As summarized by Matt Ridley, "the gene that most defined susceptibility to asthma in blacks was not the same that most defined susceptibility in whites, which was different again from the gene that most defined susceptibility in Hispanics." (p. 75)
Why could this be? Michael Wade presents a plausible explanation for this failure to replicate the results in different populations: that the genetic background is different across the different populations. 5 The different populations could have somewhat different allele frequencies of genes that act as modifiers of the genes that have a large effect on asthma propensity. This would be consistent with we know about genetic variation in human populations: differences among populations are usually ones of frequency, not of kind. Because of different frequencies of modifier alleles across the populations, a particular gene may explain more of the variation in asthma sensitivity. Determining whether this is the explanation for the different results obtained for asthma susceptibility will require first isolating the modifier genes and then testing whether their frequencies vary in different populations.