Here's a puzzle. Consider the case of two brothers, when each had reached the age of 20. One of them — call him Al — was a typical young male. His brother, Bo, however, was not at all typical of young males at this age. Bo looked more like a preadolescent male: poorly developed muscles, absolutely no facial hair, and a voice to match. Their mother was understandably worried about Bo, and soon after his 20th birthday finally convinced him to see a doctor. Once Bo removed his clothes, the doctor immediately noticed that something was missing — his genitals. A closer inspection revealed that he did in fact have genitals but nothing like those you would expect of a 20-year-old male. They seemed vestigial. The doctor's diagnosis was Kallmann syndrome, a disorder of sexual development. What's puzzling is this: Al and Bo are identical twins, nature's clones. So what happened to Bo? And why didn't it happen to Al?
Kallmann syndrome is an odd-seeming mixture of developmental defects. Not only is sexual development affected, but so too is the sense of smell. Those who suffer from this disorder have greatly impaired olfaction; some have no sense of smell whatsoever. … It is also noteworthy, therefore, that even though only Bo's sexual development was impaired, both Al and Bo have an impaired sense of smell; both, in fact, have Kallmann syndrome. Why is Bo's case so much more severe? Kallmann syndrome is generally considered a genetic disease. Yet Al and Bo share whatever genetic defects may have contributed to Bo's condition. What is it that they don't share? The story of Al and Bo is based on a real case study, one of the more dramatic examples of discordance in genetically identical twins. … Their discordances sometimes result from essentially random processes at the biochemical level. We are familiar with one form of biochemical randomness, called mutation, which alters the DNA sequence. It is possible but highly unlikely that Bo's DNA mutated after the fertilized egg split, in which case the twins would be genetically different. It is much more likely that the differences in Al and Bo are epigenetic in nature. The term epigenetic refers to long-term alterations of DNA that don't involve changes in the DNA sequence itself. Either Al's DNA was epigenetically altered in a way that meliorated his Kallmann syndrome, or Bo's DNA was epigenetically altered in a way that exacerbated it.
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Reprinted from Epigenetics: The Ultimate Mystery of Inheritance by Richard C. Francis. Copyright © 2011 by Richard C. Francis. Used with permission of the publisher, W.W. Norton & Company Inc.