SEARCH STRING: no:03477947
DATABASE: FastDoc
REFERENCE NO: 03477947
AUTHOR: Travis, John
TITLE: Repeating DNA linked to schizophrenia
SOURCE: Science News
VOL/ISSUE NO: v152n19
PAGE(S): 294
DATE: Nov 8, 1997
COPYRIGHT: Copyright Science Service, Inc. 1997
A genetic stutter already convicted of causing
Huntington's disease and several other neurodegenerative
disorders is now under suspicion as an accomplice in the
triggering of mental illnesses such as schizophrenia.
Investigators have found that in a group of people with
schizophrenia, this unusual stutter, known as a CAG
repeat, tends to be significantly longer than normal in a
gene that helps control the flow of potassium ions into
brain cells.
This unexpected finding is bolstered by earlier research
suggesting that a schizophrenia-related gene exists in
the region of chromosome 22 where the newfound gene
resides, notes J. Jay Gargus of the University of
California, Irvine, who presented the work last week at
the American Society of Human Genetics meeting in
Baltimore.
In light of previous failures to replicate studies
linking a gene to mental disorders, Gargus and other
scientists caution that the new finding must be confirmed
by studying many more people with schizophrenia.
"This is an interesting candidate and it should be
tested, but it shouldn't be considered a gene that
contributes to schizophrenia at this point," says CAG
repeat researcher Christopher A. Ross of Johns Hopkins
University Medical Institutions in Baltimore.
"Stories of these genes have been wrong in the past and
will be wrong in the future. Only time will tell," agrees
Michael J. Owen of the University of Wales College of
Medicine in Cardiff.
Gargus and his colleagues normally study ion channels,
complexes in cell membranes that govern ion movement into
and out of cells. After finding a rat gene that encodes a
potassium channel, they unearthed the human version and
noticed it had CAG repeats.
This feature-a repetition of the nucleotide sequence
cytosine, adenosine, and guanine-has become a theme in
genes underlying neurological illnesses (SN: 6/10/95, p.
360). The repeats apparently trigger problems by adding
extra copies of the amino acid glutamine to the protein
normally encoded by a gene.
Gargus and his colleagues therefore wondered if their
gene, with its CAG repeats, might cause some illness. "We
wanted a nice, rare neurodegenerative disease," he
recalls.
The scientists mapped the gene to the chromosome 22
region deleted in velocardio-facial syndrome, an
inherited developmental disorder marked by an increased
incidence of manic depression and schizophrenia (SN:
1/4/97, p. 7).
Working with scientists at the University of Pittsburgh
and in Europe, they determined the number of the gene's
CAG repeats in about 150 people with schizophrenia and
about 150 without the disorder. Although the number of
repeats ranged from 10 to 28 in both groups, statistical
tests showed that, on average, people with schizophrenia
had significantly more repeats.
Since the number of CAG repeats may vary less among
related people, some scientists suggest that the gene's
link to schizophrenia would have been more compelling if
the researchers had compared CAG repeat numbers between
people with the mental illness and their unaffected,
close relatives.
It's unclear how CAG repeats in the newly identified gene
could increase susceptibility to schizophrenia. Gargus
and his colleagues speculate that extra repeats lead to
abnormally active potassium channels, which suppress
proteins called NMDA receptors. Drugs that inhibit this
receptor, such as PCP, induce schizophrenialike symptoms,
and some antipsychotic drugs activate the receptor, says
Gargus.
As they seek to confirm their gene's link to
schizophrenia, as well as determine its role in other
mental disorders, such as manic depression, the
investigators plan to examine where in the brain the gene
is active. In the hope of develop ing new drugs for
schizophrenia, they will also search for compounds that
block the channel. -J Travis
------------------------------------------------------------
Thanks for using FirstSearch.
This e-mail account is only for distribution of FirstSearch documents.
Please contact your librarian with comments or concerns.
------------------------------------------------------------
-
To unsubscribe from this list: send the line "unsubscribe linux-kernel" in
the body of a message to majordomo@vger.rutgers.edu