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[History] MORMON GENE STUDY

Article Published: Saturday, August 07, 2004 - 7:12:23 AM PST

Mormon genes are subject of major research study

By Kirk Johnson
The New York Times

SALT LAKE CITY -- Utah is justly famous for its big families, with cousins piled on cousins, uncles from here to Tuesday, and roots stretching back to the Mormon pioneer days. And what once appeared to be a regional quirk is increasingly viewed by scientists as something more: a near-perfect laboratory, arrived at by complete accident, for the study of human kinship.

Mormon genes are hot.

Utah DNA is being used for an international study that seeks to identify chromosomes linked to diseases such as asthma and diabetes. Other researchers are studying how the genes for left-handedness or longevity or even the ability to taste bitter foods have moved through the Utah gene pool over time. A nonprofit foundation here is compiling a giant genetic database that will try to pinpoint -- after a quick swab of a person's cheek for a DNA sample -- where the person's ancestors came from.

"Utah's contribution to genetics has been enormous," said Mark S. Guyer, a division director at the National Human Genome Research Institute in Maryland.

To a scientist, the single greatest attraction of Utah -- and its biggest distinction in a nation of rootless wanderers -- is stability. For more than 150 years, largely because of the Mormon church, the state has been a magnet to people who mostly stayed put. A relatively small founding population was fruitful and multiplied -- aided in the 19th century by polygamy, adding a unique wrinkle to the genetic trail. With its emphasis on family records and genealogy, the Mormon church, officially the Church of Jesus Christ of Latter-day Saints, then created a treasure trove of details about those people.

The rest was left to science. In the 1970s, researchers at the University of Utah began melding church records with every measure of public health and mortality they could find, creating a vast database -- containing 1.6 million people -- that scientists can use to cross-index family trees with cancer clusters and disease patterns and death rates.

In the 1980s, an in-depth study of the genetic makeup of 50 big Mormon families was begun. Those families, containing more than 650 people, have since been revisited again and again for study. Their identities are closely held secrets, say scientists at the university's department of human genetics, but the raw data of the group's cellular structure has been shared all over the world.

"We know probably more about the definitions of the DNA segments in those individuals than in any others, anywhere," said Jean Weissenbach, the director of the French National Sequencing Center, which used samples from the Utah families in its work on the multinational effort to define and delineate DNA, called the Human Genome Project, which was completed last year.

But there is also something else involved -- call it marital fidelity. On average across the United States, about 5 percent to 10 percent of people who have DNA tested for various reasons are not really the sons or daughters of the person they had though of as dad, scientists say.

In Utah, or at least in the families at the heart of the various genetics studies over the years, the rate of "nonpaternity," as it is called, is less than 1 percent, private industry researchers and University of Utah scientists say.

"They stick to their knitting," said Mark Skolnick, the chief scientist at Myriad Genetic Inc., which is one of the biggest companies in the state's emerging genetics corridor, clustered around the University of Utah, where Skolnick was a professor and a pioneer in the discovery of the gene marker for breast cancer.

People like Norm Jones also help explain how Utah is different. A missionary who serves at the Mormon church's Family History Library across the street from the downtown temple, Jones, 69, is a living embodiment of what the culture of genealogy can produce.

He can trace his roots to the 1840s in Salt Lake City, through an extended web of intermarried families in the many decades since. He can print out his family pedigree with the tap of a few computer keys. He knows which of his ancestors walked across the Plains to Utah, and which could afford a wagon.

Quite often, Jones said, he wanders up to help a library patron and finds that they have a common ancestor.

"After a while, you're related to everybody," he said.

There are certainly other places where genes and genealogy have merged. Researchers in Iceland, where many family histories go back a thousand years or more, have created detailed genetic family trees. Other groups, like the Amish and Mennonites in the United States and Canadians from Quebec have also been studied for their genetic distinctiveness.

What Utah offers, researchers say, is partly the power of numbers. The life and health histories of 1.6 million Utahans, living and dead, have been incorporated into the Utah Population Database run by the Huntsman Cancer Institute at the University of Utah. Iceland, by contrast, which is probably Utah's nearest competitor as a geneticist's paradise, has only about 280,000 people. Iceland's population, because of its isolation, is also much more inbred than Utah's, where the gene pool has been regularly infused with new blood as converts to the church came here over the decades. About 70 percent of Utah's population is Mormon.

Mormons themselves say that the church's emphasis on the importance of family created a natural bridge to the more scientific definitions of kinship. Researchers say there is also a strong community sense that makes people want to contribute, even if it does not help them or their families.

"Among Christian religions, we probably stand out as the one probably most interested in family ties; we are a record-keeping and record-gathering people," said Jay W. Butler, the associate international legal counsel in the church's office of general counsel. "All of that contributes to the uniqueness of Utah as a fertile ground for the research of families."

There are limits, however, to what Mormon leaders will condone in using church records for genetic research. The church strongly opposes abortion, for example, and also frowns on the use of alcohol, tobacco, coffee and tea by church members. So, Butler said, the church opposes any research that might lead to more abortions, for example, a gene that identified the likelihood of a birth defect, or might encourage the use of alcohol or tobacco, for example a gene that suggested reduced health effects from smoking or drinking.

Managers of the population database at the University of Utah, which receives dozens of research proposals a year, say they recall only a couple of outright church vetoes over the years. Since then, they say, they have learned to cull the ideas that will not be approved. More than 50 genetic research projects are now under way, they said, on health issues such as psoriasis, autism and arthritis.

Other pieces of Mormon history that the church is sometimes reticent to talk about, such as polygamy, are also good things for science, researchers say. The taking of multiple wives was practiced by a minority of mostly prominent Mormons for two or three generations, from the 1840s to 1890, when the church said monogamy was the way of the future.

But polygamy left a big imprint. In a state where thousands of families are descended from polygamists, the genes of a relatively small group of men have been amplified and etched into the biological record, researchers say, as though with a highlighting pen.

One male whose genes might have carried a particular mutation, for example, could have fathered dozens of children through multiple wives -- and had sons who in turn took multiple wives themselves and had equally big families. Scientists tracing that gene through the family branches where it was found and those where it was absent can learn a great deal about how very specific traits move through succeeding generations.

Some Mormon-based organizations are now trying to bring modern genetics back full circle, to reinforce traditional church genealogy.

The Sorenson Molecular Genealogy Foundation, the nonprofit group here that's compiling a global genetic database to assist Utahans and others in finding their roots, is housed in a nondescript building a few miles from the sleek new research centers at the University of Utah. The scientists creating the database were hired by a billionaire medical equipment entrepreneur, James LeVoy Sorenson. The chief scientist at the foundation, Scott R. Woodward, said the goal was to have a DNA sample of 100,000 people within the next few years, focused primarily on Western Europe -- the place from which most Utahans are descended. About 40,000 samples are already available, he said.

When the database is completed, Woodward said, a person should be able to walk into the office, provide a DNA sample, and get a report back saying what place -- perhaps down to the town or county, if not a region -- his or her genes are most likely from.

"Genealogy was the starting place," Woodward said. "Genetics has now made the tools to go back and verify the genealogy."

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