REPORTERS AND EDITORS NOTE:  Gottesman accompanied Rex Cowdry,
director of the National Institute of Mental Health, on a
schizophrenia-teaching mission to India Feb. 14-25.  He can be
reached in the U.Va. psychology department at (804) 924-0661 or by
e-mail at iig@virginia.edu


	INTERNATIONAL RESEARCH TEAM ADVANCES 
UNDERSTANDING OF SCHIZOPHRENIA GENETICS

	CHARLOTTESVILLE, Va., Feb. 27 -- As the "Atomic Age" draws
to a close, people seeking a moniker for the coming century might do
well to dub it the "Genetic Age."  Over the past 20 years, rapidly
improving methods for manipulating DNA have made the landscape of
the 23 pairs of human chromosomes -- each of which contains
thousands of genes -- more familiar and scientists are now on the
verge of a new age of discovery.  Some 15,000 "signposts" to
locations on the human gene map have been constructed in recent
years and this number will double within a few more years.
	Using a variety of techniques to determine the sequence of
DNA subunits, gene hunters have able to track down the defective
genes responsible for such conditions as cystic fibrosis and
Huntington's Disease.
	Other diseases present a more complicated picture.  They
involve anomalies in more than one gene and probably also require
environmental triggers to initiate the disease process.  Such
polygenic conditions include diabetes, some kinds of cancer and,
probably, schizophrenia.
	Irving I. Gottesman, the Sherrell J. Aston Professor of
Psychology at the University of Virginia, first theorized about the
possibility that schizophrenia is a polygenic disorder nearly 30
years ago.  Recently, an international collaboration has provided
strong evidence that Gottesman's theory is correct.  Along with 27
co-investigators, Gottesman studied the DNA of 456 schizophrenics
from 276 families in a dozen countries including China, Ireland,
Sweden and the United States.
	"Our recent studies differ from those of other teams in
several important respects," says 
Gottesman.  "First, we used a very conservative definition of
schizophrenia.  This ensured that those people who actually have
schizophrenia (and their families) would be included in further
tests.  Second, we searched all of the chromosomes for evidence of
schizophrenia-causing genes, instead of focusing on just a few
chromosomes as other groups have done.  Finally, we used a two-step
procedure to distinguish the genuine links between our 'markers' and
possible schizophrenia genes from any false links."
	As reported in the November issue of the journal
Nature-Genetics, the team found two locations -- on chromosomes 9
and 20 -- that had not been previously linked to schizophrenia.
They also gave support to sites on chromosomes 6, 8 and 22, which
had been detected previously by other researchers.
	"These developments parallel the progress seen in studies of
insulin-dependent diabetes, where eight different gene locations
have been identified as being linked to appearance of the disease,"
said Gottesman, the recipient of numerous awards for his long-term
research on schizophrenia.
	According to the model proposed in 1967 by Gottesman and his
late colleague Dr. James Shields, multiple genes act in a system to
bring about the symptoms of schizophrenia.  "The more of these
'schizophrenia-vulnerability' genes a person has, the greater the
chance that environmental stressors will trigger a clinical episode
of the disease," said Gottesman, who notes that schizophrenia
affects one of every 100 adults worldwide.
	According to Gottesman, "all of the investigators in this
team used the same conservative diagnostic measure to identify
persons with schizophrenia or schizo-affective disease.  "Through
these interviews, five large Icelandic families with 37
schizophrenics among the 93 members were found.
	By thickly plastering the DNA of these families with
laboratory-made DNA markers, the researchers found 26 sites to be
associated with the appearance of the disease itself.  Of these, the
10 most promising sites were looked for in DNA taken from other
schizophrenia families around the world.  This second round of
searching yielded sites on chromosomes 6, 8, 9, 20 and 22, all of
which appear to be statistically linked to schizophrenia.  The
scientists are now attempting to clone the genes in these regions in
order to determine their exact composition and action.
	"A clearer understanding of the several genes believed to be
involved in schizophrenia will enable doctors to make definitive
diagnoses of this disease.  In the more distant future, we
anticipate being able to attack the root cause of schizophrenia by
treating its genetic underpinnings," said Gottesman.
###
February 26, 1996