GENOMIC DNA STABILITY AND
SCHIZOPHRENIA IN TWINS
Cassandra L. Smith, Giang H. Nguyen,
Joseph Bouchard, Monica G. Boselli, Linda G. Tolstoi, Louis Keith, Clinton
Baldwin, and Victoria L.H. Herrer
Boston University
Targeted genomic differential display
(TGDD) fingerprinting measured the number of differences in pools of anonymous
restriction fragments selected to contain (CAG)n repeating sequences in 12
twin-pairs classified as monozygotic (MZ), and 18 unselected sib-pairs from 7
families. Eight twin-pairs were affected by Schizophrenia four
concordantly and four discordantly. Although, TGDD fingerprints reflects,
rather than represent an exact composition of pools, it was expected that the
genomes of MZ twin-pairs would be almost identical, whereas sib-pairs would
have, on average, 50% similarity. MZ twins concordant for disease, and
unaffected MZ twins, had the expected similarity level detected by TGDD.
However, the number of differences in MZ twin-pairs discordant for Schizophrenia
overlapped those of sib-pairs. If these twins are truly MZ, then the large
number of within pair differences must (1) reflect DNA changes that arose after
the twinning event, and (2) represent a genome-wide instability, at least,
around (CAG)n sites. If DNA instability is a characteristic of Schizophrenia, it
must be limited to the pre-twinning period in concordantly ill twin-pairs as
such changes are invisible in these experiments. Genomic instability in
Schizophrenia explains why Schizophrenia is linked to chromosomal abnormalities,
genes, and gene localization that map to genomic regions containing fragile
sites, and/or (CAG)n sequences spread throughout the genome support.