The search for a gene that produces twins could answer multiple questions

November 24, 1994|By Richard Saltus | Richard Saltus,Boston Globe

In most families, the birth of twins is a dizzying, once-in-a-lifetime event. But in some families, babies arrive two at a time with mystifying frequency, and the tendency can pass from one generation to the next like red hair or musical talent.

"Whatever causes it, we've got it in my family," says Marjorie Topaz, a Newtonville, Mass., consultant who has boy-girl twins almost two years old. "I'm a twin myself," says Ms. Topaz, a member of the Massachusetts Mothers of Twins organization. "My mother had three sets of twins. My grandmother was a twin. I have cousins who are twins."

Could there be a gene for twinning? Very likely.

Genes don't seem to play a role in identical twins -- which occur when a fertilized egg splits in two. But scientists reported last month that evidence is mounting that an inherited factor -- one gene or several -- affects the tendency to have fraternal twins. They come along when a woman produces two eggs simultaneously and they are fertilized by separate sperm.

The findings have prompted a search on three continents for a "twinning gene," which got a further boost from researchers in New Zealand who are pursuing a particular stretch of DNA they believe increases litter size in a strain of Merino sheep. Tantalizingly, there's evidence that the DNA sequence may have a counterpart in humans.

The search is motivated by more than simple curiosity, because the quest could illuminate a fundamental question: Why do women normally produce just one egg a month, but under some circumstances -- including the presence of a mutant gene -- turn out more than one?

If a gene for multiple ovulation can be identified, it "could be the clue for a lot of questions about fertility and infertility in women," said Dorret Boomsma, a psychologist at the Free University of Amsterdam.

A lot of folklore

There is a lot of folklore about twins, says Nicholas Martin, a geneticist at the Queensland Institute for Medical Research in Australia. His own research and a recent unpublished study by Ms. Boomsma confirm that "the pattern of inheritance is very irregular, and no study has really given us the last word on what laws of genetics would describe it," he said in a telephone interview.

Twins make up only about 1 percent of births, but as you might zTC suspect by looking around a typical shopping mall, they are becoming more prevalent. This is due, at least in part, to the use of fertility drugs and the rising numbers of births to older women, who are more likely to have multiple pregnancies. In 1992, according to the National Center for Health Statistics, 95,372 infants were born live in twin deliveries in the United States. About two-thirds were fraternal.

Last month, at the meeting of the American Society of Human Genetics in Montreal, Mr. Martin and geneticist Carolyn Lewis of the University of Utah reported a study that points to a strong genetic influence on twinning.

Mr. Martin and Ms. Lewis analyzed an Australian database containing records of 6,600 twin births. They calculated that if a woman has twins, the odds that a sister will have them is nearly 70 percent greater than average. And a woman who is a twin has 2 1/2 times the usual chance of giving birth to twins herself.

Similar findings emerged from the study by Ms. Boomsma and her colleagues in Amsterdam. But neither study has been able to establish for certain that the tendency to have twins is passed down according to the classic patterns -- like dominant or recessive inheritance -- of most inherited traits.

The supposed "twinning gene" can be carried by males and passed on to their daughters. That accounts for the folklore idea that having twins "skips a generation" -- it doesn't happen if there are few or no women to bear the twins.

Not identical twins

Rates of identical twins are similar around the world and don't appear to be influenced by genes, ethnic origin, fertility drugs or anything but chance, researchers say.

The story is vastly different with fraternal twins, who are the result of multiple ovulation and are no more genetically related than any other siblings. Rates of fraternal twinning vary dramatically with age, racial background and other factors. For example:

* Older mothers have more twins and other multiple births, with the rate peaking at age 37.

* The more children a woman has had, the more likely she is to have twins.

* Women of African descent have the most fraternal twins, and Asian women have the fewest. Caucasian women are in between. Australian geneticist Martin said in some parts of Africa, the rate of twins is more than 20 pairs per 1,000 deliveries, while in Japan, at the other extreme, the rate is 2.3 per 1,000. In Western Europe and America, the rate is about 8 per 1,000.

Mr. Martin said there's no good explanation for these variations, or any obvious reason why evolution would preserve twinning genes in some populations more than others.

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