assignment

  Collapse panel

Other formats:

· Citation/Abstract

Top of Form

The link you clicked points to a document not stored in ProQuest. Depending on the source, or type of publication providing the document, it may not be available.

OK

Bottom of Form

More like this

See similar documents

See similar documents

Dark Prophecy: New Test Tells Whom A Crippling Disease Will Hit -- and When --- Gene Responsible for Ataxia Has Same Flaw as Those Causing Some Cancers --- The `Stutter' in the DNA

false By Marilyn Chase . Wall Street Journal , Eastern edition [New York, N.Y] 08 Dec 1993: PAGE A1.

Turn on hit highlighting for speaking browsers

Abstract (summary)

Translate Abstract Undo Translation TranslateUndo Translation

Press the Escape key to close

FromTo

Translate

Translation in progress...

[[missing key: loadingAnimation]]

The full text may take 40-60 seconds to translate; larger documents may take longer.

Cancel

During her Christmas break, the Charleston, S.C., student plans to be tested for a gene that causes ataxia, a disease without a cure that destroys the brain cells governing muscle control. The disorder crippled and ultimately killed her father in middle age. Because of a recent breakthrough in genetic research, the 21-year-old Miss Snider will be able to find out whether she inherited the disease, and, if so, how soon and how hard ataxia may strike her.

In the immediate years ahead, millions of people will face similar dilemmas, as researchers continue to discover the flaws in human genes that cause diseases. The gene responsible for ataxia was identified earlier this year by Harry Orr at the University of Minnesota in Minneapolis and Huda Zoghbi at the Baylor College of Medicine in Houston. The researchers then made another significant discovery: The gene, known as SCA1, has a flaw, a strikingly visible mutation that is common to other inherited neurological disorders, as well as some cancers.

Bearers of the cancer gene may be dismayed to find out they have it, but they will be in a position to get constant monitoring and early treatment, which could save their lives. For victims of an incurable genetic disease such as ataxia, testing is like judgment day. Moreover, they face a new and chilling kind of biological prophecy, because the number of triplet repeats within the SCA1 gene can be used to forecast roughly when and how severe the onslaught of ataxia may be.

During her Christmas break, the Charleston, S.C., student plans to be tested for a gene that causes ataxia, a disease without a cure that destroys the brain cells governing muscle control. The disorder crippled and ultimately killed her father in middle age. Because of a recent breakthrough in genetic research, the 21-year-old Miss Snider will be able to find out whether she inherited the disease, and, if so, how soon and how hard ataxia may strike her.

In the immediate years ahead, millions of people will face similar dilemmas, as researchers continue to discover the flaws in human genes that cause diseases. The gene responsible for ataxia was identified earlier this year by Harry Orr at the University of Minnesota in Minneapolis and Huda Zoghbi at the Baylor College of Medicine in Houston. The researchers then made another significant discovery: The gene, known as SCA1, has a flaw, a strikingly visible mutation that is common to other inherited neurological disorders, as well as some cancers.

Bearers of the cancer gene may be dismayed to find out they have it, but they will be in a position to get constant monitoring and early treatment, which could save their lives. For victims of an incurable genetic disease such as ataxia, testing is like judgment day. Moreover, they face a new and chilling kind of biological prophecy, because the number of triplet repeats within the SCA1 gene can be used to forecast roughly when and how severe the onslaught of ataxia may be.

You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer

Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer Translations powered by LEC.

Translations powered by LEC.

Full Text

· Translate Full text Undo Translation TranslateUndo Translation

Press the Escape key to close

FromTo

Translate

Translation in progress...

[[missing key: loadingAnimation]]

The full text may take 40-60 seconds to translate; larger documents may take longer.

Cancel

· Turn on search term navigation Turn on search term navigation

· Jump to first hit

Amy Jo Snider, a college senior, has put her career plans and romantic life on hold until she settles a gnawing question about her genetic legacy.

During her Christmas break, the Charleston, S.C., student plans to be tested for a gene that causes ataxia, a disease without a cure that destroys the brain cells governing muscle control. The disorder crippled and ultimately killed her father in middle age. Because of a recent breakthrough in genetic research, the 21-year-old Miss Snider will be able to find out whether she inherited the disease, and, if so, how soon and how hard ataxia may strike her.

"I want to be tested before I start to show symptoms," she says unflinchingly. "I'm graduating in May, and I have to start planning my life." As agonizing as the knowledge might be, she says the uncertainty is worse. "If I'm in limbo, it's not fair to people around me," she says. "I can't deal with not knowing."

In the immediate years ahead, millions of people will face similar dilemmas, as researchers continue to discover the flaws in human genes that cause diseases. The gene responsible for ataxia was identified earlier this year by Harry Orr at the University of Minnesota in Minneapolis and Huda Zoghbi at the Baylor College of Medicine in Houston. The researchers then made another significant discovery: The gene, known as SCA1, has a flaw, a strikingly visible mutation that is common to other inherited neurological disorders, as well as some cancers.

The mutation -- which SCA1 shares with the genes that cause neurological diseases such as Fragile X, Huntington's Disease, Kennedy's Disease and myotonic dystrophy -- consists of an abnormal repetition of three-letter segments of the genetic code, a kind of genetic "stutter."

The ability to identify these "triplet repeats" may greatly accelerate the discovery of other genes that cause disease, and provide clues to the mechanics of inherited disease. Last week, two research teams announced that they looked for such code repeats to discover the gene that can lead to cancers of the colon, uterus and ovary. In short order, a blood test will be able to identify the one out of every 200 people who carry that cancer gene.

Bearers of the cancer gene may be dismayed to find out they have it, but they will be in a position to get constant monitoring and early treatment, which could save their lives. For victims of an incurable genetic disease such as ataxia, testing is like judgment day. Moreover, they face a new and chilling kind of biological prophecy, because the number of triplet repeats within the SCA1 gene can be used to forecast roughly when and how severe the onslaught of ataxia may be.

The discovery of SCA1 crowned a fervent eight-year collaboration with a moment of quiet eureka.

In 1985, Dr. Zoghbi in Houston was studying ataxia in a large African-American family in Texas, while Dr. Orr in Minneapolis was tracking the disease in Midwestern clans, many of Dutch descent. In a field rife with fierce rivalries, the two researchers shucked their egos and shared their data.

The Zoghbi-Orr collaboration is a "spectacular story," says Robert Currier, a neurologist and ataxia specialist at the University of Mississippi. "They could have hidden information from each other. They could have gone at it tooth and nail. But they shared it all the way."

"Neither lab could move through it alone," Dr. Orr explains. He likens their gene quest to the job of a plumber who gets a service call from "somewhere in the United States," and then must locate the trouble spot in the right state, city, block and house. First, they mapped the area using certain DNA markers -- unique segments of genetic code -- narrowing their search to a part of chromosome six. Then they cloned great swatches of genes in yeast for further study.

In early 1993, Drs. Orr and Zoghbi divided up their target area, using probes to examine it bit by bit. Smack in the middle, they spied a peculiar gene in which three chemical building blocks of DNA -- cytosine, adenine and guanine -- came together to spell out 'CAG' over and over again. In a comparative analysis of DNA from healthy and sick people, they found normal genes held 25 to 36 of these `CAG' repeats, while mutant genes expanded, containing 43 to 81 CAG repeats -- blatant typos in the biological blueprint.

"That was when we knew we had the gene," remembers Dr. Orr. "I phoned her and said: `I think we've got it.'"

"This is the sort of thing you dream about as a scientist," he says. "When it happens, it leaves you speechless."

Their elation was tempered by the sober discovery that they could count the `CAG' repeats and predict -- to within a decade or two -- how soon and how hard the disease would strike. The more CAG repeats, the earlier and more severe the ataxia. While the link wasn't perfect, Dr. Orr says, "You could certainly say whether the ataxia is going to be a juvenile case, a mid-adult case, or a late-adult case."

"We were amazed by it," says Dr. Zoghbi. "I decided to put it on a graph. When I saw what it looked like, I said, `Oh my goodness.' It was chilling."

Scientists had earlier observed links between such "triplet repeats" and time of diagnosis in Huntington's Disease. But these earlier links were not as clearly predictive as the ones found by Drs. Orr and Zoghbi, says C. Thomas Caskey, a noted Baylor geneticist. "Their data is beautiful."

The growing significance of triplet repeats in human genetics has helped solve a puzzle that has long stumped classical geneticists schooled in the tradition of the monk Mendel with his sweet peas. Since genes were supposed to be stable, how could inherited diseases worsen from generation to generation? One answer: mutations that grow. In the SCA1 gene, research has shown that the number of triple repeats can increase from generation to generation, triggering a worsening of the illness.

"The concept that genes can expand, causing increasingly severe disease, is a phenomenon that's new to us," says Arnold Gale, a neurologist and spokesman for the Muscular Dystrophy Association.

"It's gratifying and a bit alarming to find five diseases pop up with this same genetic mechanism," adds David Nelson, another Baylor geneticist. Beyond linking SCA1 with the retardation of Fragile X, the movement disorder and dementia of Huntington's and the muscular degeneration of Kennedy's and myotonic dystrophy -- and with colon cancer -- experts feel more such genes may soon be unearthed.

"I can't begin to tell you how much excitement there is. Finally, after all these years, there is hope" for better diagnosis and treatment, says Donna Gruetzmacher, spokeswoman for the National Ataxia Foundation, which represents about 150,000 patients suffering from 60 types of ataxia. There are no firm figures on how many people suffer from SCA1 ataxia, which often results in complete disability and death.

"I'd like them to find the gene and remove it -- cut it out, so I would be fine," says Tereess Bastion, a 30-year-old marketing specialist in Long Beach, Calif. Ms. Bastion lost her mother and brother to ataxia, before the disorder unhinged her own sense of balance.

Her wish for a procedure to disarm the ataxia gene seems a long shot at best. The neurons targeted by ataxia are tucked away in the cerebellum and brain stem, beyond the reach of current gene-therapy tools, says Dr. Orr.

He is more optimistic about drug therapy. He and Dr. Zoghbi are genetically engineering a mouse strain to study how the SCA1 gene produces a protein that kills brain cells. If such a protein is found, researchers might design molecules to block it.

Until such designer drugs are devised, the SCA1 gene test acts as a kind of biological crystal ball. Rather than waiting for loved ones to stumble and slur their speech -- the first symptoms of ataxia -- families at risk can be screened. But the test may simply replace fear of the unknown with fear of the known.

"A lot of people are scared to find out. Put yourself in their place," says Jim Devlin, leader of an ataxia support group in Marina Del Rey, Calif. Wheelchair-bound and fiercely articulate, the 57-year-old Mr. Devlin forces out a painful question: "If I were your brother," he asks, "would you want to know?"

For those without symptoms, a genetic prophecy like SCA1 resembles an evil spell from a fairy tale. "For these people the spell is cast," says Larry Schut, a Minneapolis neurologist whose family tree was blighted by ataxia. "It may be 20 or 30 years, but they will get it." Career, family and insurance decisions hang in the balance. "I liken it to telling someone they have an HIV-positive blood test, but no signs of AIDS," says Dr. Schut. "We're dealing with people who are perfectly normal . . . but who will become ill. You don't know who's going to jump off the bridge, or who will take it well."

That's why Dr. Currier in Mississippi approaches screening gingerly. Ten years ago, long before a precise gene test was available, he gave a gifted young guitarist a rough prognosis of ataxia, based on older tissue-typing technology. Still healthy, the youth took it stoically, then later fired a gun into his chest.

Emotional turbulence unleashed by testing can rend families. In a recently tested Pacific Coast clan, one family member who has the gene lashed out at relatives who tested negative, accusing them of collusion with researchers.

Such ruptures are "very poignant and very predictable," says Nancy Wexler, a Huntington's expert. "Imagine the rifts in the nuclear family. It's explosive. People who are unaffected feel guilty. People who are affected feel enraged."

She adds, "pre-symptomatic screening needs to be done with extreme caution and extensive counseling." Joseph Martin, a neurologist who is chancellor of the University of California at San Francisco, believes that "absent treatment, only a minority of people will want to know."

Jane Blakely, a telephone company employee in Tacoma, Wash., was one of that minority. A single woman of 45 who has spent the last dozen years caring for an elderly mother with ataxia, she says, "I wanted to know . . . . We had to do some family and financial planning."

So when the test became available this past summer, Ms. Blakely submitted her blood sample -- and got good news. "Mine was normal. I was just ecstatic," she says. But her relief is bittersweet. "I chose not to have children. I shied away from any involvements," she says. Had she known her genetic fate sooner, she adds, "I might have acted differently."

Conversely, some ataxia patients now are choosing to conceive children -- only to face a prenatal testing dilemma.

In Waynesboro, Miss., Pam Shima , a court reporter with mild ataxia who already had two sons, became pregnant again this year. She underwent prenatal screening, but miscarried just after her fetus tested negative for the gene.

Mrs. Shima now says she won't test her sons, aged two and 13. Life abounds with risks, she reasons: "When my teenager gets behind the wheel of a car and says `See you after midnight,' then I'll be worried -- more so than whether he'll be in a wheelchair at age 45."

For now, she admits, "I'm more worried about whether I'll be around to see my youngest son play baseball."

In Long Beach, Calif., Dawn Dizon, a 31-year-old aircraft engineer, is happily expecting her first child in February. She suffers from early ataxia, and strives to keep it in check with tremor-controlling drugs and exercise. But she didn't undergo prenatal screening of her fetus.

"Our child has a 50-50 chance of getting it," she concedes. But she thinks that "by the time it's old enough to have symptoms, there will probably be a treatment." Besides, she says, life is a gift, even when illness is part of the legacy. "I wouldn't have wanted my parents not to have me just because I happen to have ataxia."

Previewing one's genetic fate strikes some as a way to rational, ordered existence, and others as a road to spiritual ruin. "I'm very sure I can deal with the knowledge," says Ms. Snider, the Charleston college student, of her forthcoming test. "It's not going to ruin my life. But it will change it." Testing positive may mean forgoing having children, or giving up her dream of becoming a speech therapist. Above all, she acknowledges, it may shorten her life.

"If I know I'm going to be contracting symptoms," she declares stoutly, "I'll have to achieve things sooner."

But to Wanda Cox, a Los Angeles computer specialist who was surprised by ataxia when she fell off her bike at age 40, a predictive test might have hurt more than it helped. "If you're told you'll be sick by age 40, you'll look for symptoms," she says, arguing that determinism leads to despair.

"If I knew I was going to be hit by a car next week, life would be irrevocably changed," says Ms. Cox. "Do I want to know? Hell, no."

Credit: Staff Reporter of The Wall Street Journal

Word count: 2218

Show less

You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer

Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer Translations powered by LEC.

Translations powered by LEC.

Copyright Dow Jones & Company Inc Dec 8, 1993

Indexing (details)

Cite

Title

Dark Prophecy: New Test Tells Whom A Crippling Disease Will Hit -- and When --- Gene Responsible for Ataxia Has Same Flaw as Those Causing Some Cancers --- The `Stutter' in the DNA

Author

By Marilyn Chase

Publication title

Wall Street Journal , Eastern edition

Pages

PAGE A1

Number of pages

0

Publication year

1993

Publication date

Dec 8, 1993

Year

1993

Publisher

Dow Jones & Company Inc

Place of publication

New York, N.Y.

Country of publication

United States

Publication subject

Business And Economics--Banking And Finance

ISSN

00999660

Source type

Newspapers

Language of publication

English

Document type

NEWSPAPER

ProQuest document ID

398480392

Document URL

https://login.libproxy.edmc.edu/login?url=http://search.proquest.com.libproxy.edmc.edu/docview/398480392?accountid=34899

Copyright

Copyright Dow Jones & Company Inc Dec 8, 1993

Last updated

2010-06-26

Database

ProQuest Central

Tags

- this link will open in a new window About tags | Go to My Tags

Top of Form

Bottom of Form

Be the first to add a shared tag to this document.

A tag is a non-hierarchical keyword or term assigned to a piece of information (such as this record). This kind of metadata helps describe an item and allows it to be found again by browsing or searching.

Add tags

Sign in to My Research to add tags.

Top of Form

Add tags:

Share my tags with the ProQuest user community; requires a public profile. - this link will open in a new window

Add

Use a comma to separate multiple words or phrases. For example: stars, planet, solar system. Tags can contain letters and numbers only.

Bottom of Form

Top of Form

Bottom of Form

Your tags have been saved and will be available only to you. Note: Please allow several hours processing time for newly added tags to be searchable.

OK

Your tag(s) will now be available for others in the ProQuest user community to see on this document. In addition, your Public Profile will be accessible from your shared tags. Note: Please allow several hours processing time for newly added tags to be searchable.

OK

Your tags have been saved and will be available only to you. Note: Please allow several hours processing time for newly added tags to be searchable.

Close

One or more of the tags you entered violates our acceptable use guidelines and will not be added to the document. The following tags have been added:

OK

Top of Form

Tags can contain letters and numbers only. Remove other characters from your tag in the box below and click Fix tag.

Fix tag(s):

Fix tag

Bottom of Form

· Back to top

· Contact Us

· Privacy Policy

· Cookie PolicyLink to external site, this link will open in a new window

· Accessibility

· Sitemap

Copyright © 2014 ProQuest LLC. All rights reserved. Terms and Conditions