According to the old joke, the homely but brilliant male scientist married the gorgeous but dim model figuring their children would have her looks and his brains. He was crushed -when they had her brains and his looks.

The scientist was clearly not among those studying a booming new area of genetics. If he had been, he would have known that whether a child’s traits are shaped by mom’s genes or dad’s genes isn’t a simple matter of recessiveness or dominance, let alone of pure luck, as the textbook wisdom says. Instead, some genes come with molecular tags saying (in biochemical ESE), "I come from mom; ignore me," or "You got me from dad; pretend I’m not here."

Such genes are called imprinted. Unlike re-cessive or dominant genes (such as for black or blond hair), which are composed of different molecules, these genes are identical except for the si-lencer tag sitting atop them.

The result is that if the ac-tive gene is defective, there is no working backup; a healthy but silenced gene from the other parent can’t step into the breach. In the joke, mom’s beauty genes and dad’s brainy genes were silenced, leaving mom’s dim-witted genes and dad’s homely ones to call the shots.

No one has reliably identi-fied genes for beauty or for brains, let alone figured out whether mom’s or dad’s count (or whether this explains male -pattern baldness). But real imprinted genes are hitting the big time. Imprint-ing may be one reason people seem to inherit conditions such as autism, diabetes, Alzheimer’s disease, male sexual orientation, obesity and schizophrenia from only one side of the family. At least one biotechnology company is planning to scan the entire human genome for imprinted genes (detectable with a biochemical test), hop-ing to use the data to diagnose incipient cancers.

Almost all imprinting happens automati-cally, long before birth, but in some cases it can result from outside interference. Toxic chem-icals, for instance, may eliminate the silencer tag, causing potentially harmful effects that can be transmitted to future generations. (Two points to readers who say, "Lamarck lives?")

The number of human genes where the par-ent-of-origin matters keeps rising. According to a new computer algorithm, about 600 mouse genes are likely to be imprinted, scientists at Duke University report in Genome Research. If that 2.5% rate holds for humans—and virtually every mouse gene has a human counterpart -then we have hundreds of imprinted genes, too.

Among the genes where the parent of origin matters are three on chromosome 10. Only the copies from mom, studies suggest, are turned on. One, expressed in the brain, is linked to late -onset Alzheimer’s disease. Another is linked to male sexual orientation and a third to obesity. With dad’s contribution silenced, if there is any-thing unusual in the copy from mom that will determine the child’s trait. "For Alzheimer’s, if the mutation is in dad’s gene you’ll never see an effect, but if it’s in mom’s you’re at risk for the disease," says Duke’s Randy Jirtle.

A gene on chromosome 9, linked to autism, seems to count only if it came from dad. One on chromosome 2 and one on 22 are associated with schizophrenia; only the copies from dad count. Having a family tree mostly free of these dis-eases is therefore no assurance of good health. If the disease runs on dad’s side, his gene may be defective, and that is the one that matters.

As they discover more imprinted genes, scientists are seeing that the silencing tag can be knocked off, with dire consequences. An animal study published this month suggests how. When fetal rats were exposed to two toxic chemi-cals a fungicide called vinclozolin commonly used in vineyards and a pesticide called methoxy-chlor they grew up to have slower and fewer -than normal sperm, Michael Skinner of Washing-ton State University and colleagues report in the journal Science. The abnormalities were inherited by the rats’ sons, grandsons and great-grandsons.

"That environmental toxins can induce a transgenerational genetic change is a phenome-non we never knew existed," Prof. Skinner says. How does it occur? Probably not through harmful mutations, which become rarer with each generation. But imprinting changes, of which Prof. Skinner’s group has detected 50 and counting, persist through the generations.

The ink is barely dry on the human genome project, but already researchers are onto the "second genetic code," or the pattern of silenc-ers on our DNA. Using a technology called Meth-yIScope ("methyl" is the DNA silencer), "we will map this second genetic code to see which genes are imprinted and identify any differ-ences between normal and cancerous cells," says Nathan Lakey, chief executive of Orion Ge-nomics, a closely held biotechnology concern.

Those differences may become the founda-tion for molecular diagnostic tests within three years, perhaps starting with colon cancer. Nor-mally, the copy of a gene called IGF2 that you get from dad is active, the copy from mom si-lenced. In 10% of us, though, mom’s copy has thrown off the silencer, leading to a greater risk of colorectal cancer. Detecting that unsilencing could provide an early warning of the disease.

Source: Science Journal, June 2005