Harold Schmeck Pines, Maya, ed. "Blazing the Genetic Trail." Bethesda, MD: Howard Hughes Medical Institute, 1991.

The eminent British molecular biologist Sydney Brenner once got a hearty laugh from his audience by describing how some future graduate student will define a mouse: "ATC, GCC, AAG, GGT, GTA, ATA. . . ." But every year the idea of defining an organism by the sequence of its DNA bases seems a little less farfetched.

Victor McKusick, of The Johns Hopkins University School of Medicine, notes that scientists' growing ability to read and write in the language of the genes has already explained some of the once-mysterious basic concepts of genetics. The difference between dominant and recessive traits as causes of genetic disease used to be just an abstraction based on a great deal of observation. If a genetic defect expressed itself only in patients who inherited the trait from both parents, it was called recessive; both copies of the gene coding for the trait were presumably defective, resulting in disease. If the trait was dominant, on the other hand, it meant that one defective copy of the gene was sufficient to spell disaster.

But why should some disorders require two mistakes, while others resulted from only one? Molecular biology has given a concrete and remarkably simple explanation.

"It now appears that these two categories [recessive and dominant] correspond pretty closely to the two fundamental categories of proteins: enzymatic and structural," McKusick said in a recent review of genetics research. Recessive disorders tend to result from failures in genes that code for enzymes, the biological catalysts that do much of the body's chemical work. A person who has inherited the defective gene from only one parent often goes disease-free because the normal gene inherited from the other parent produces enough of the enzyme to serve the body's needs. The disorder appears only when the person inherits the same defect from both parents and therefore lacks any working copy of the normal gene.

If the genetic defect affects structural proteins, however, for example, collagen, a key component of connective tissues and bones, one copy of the faulty gene is usually enough to cause disease. It is easy to see why. A four-engine airplane can still fly even if one of its engines fails, as long as the other engines provide enough power, but a single faulty strut that makes a wing fall off will cause the plane to crash.

The reason some genetic disorders are relatively common while most are extremely rare has also proved to be almost ridiculously obvious. The bigger the gene, the greater the chance that something will go wrong with part of it. In many cases, it seems as simple as that.

Sometimes rather subtle differences in the defects of a single gene can make a profound difference in a patient's fate, as Louis Kunkel of the HHMI unit at Harvard University learned after he and his team discovered the gene for Duchenne muscular dystrophy (DMD) in 1986. Major flaws in that huge gene result in the presently incurable DMD, a muscle-wasting disease that leaves young boys wheelchair-bound by age 12 and generally kills them by age 20, because the muscles that control breathing fail. By contrast, lesser defects in that same gene produce a much more benign disease, Becker's muscular dystrophy.

A year after discovering this gene, the team identified the protein it codes for - a previously unknown protein, now named dystrophin, which occurs in muscles in such small amounts that it would never have been found by ordinary means. Dystrophin plays a key role in muscle cells and may be involved in many other muscle diseases. Researchers are now analyzing how dystrophin functions, what other proteins it interacts with, and whether it might be replaced to interrupt the course of disease.

Experts see many more insights such as these in the future, as research in molecular genetics opens some of the "black boxes" of biology.

Read more:
The Future Of Genetic Research - Access Excellence

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