GENOMIC DNA STABILITY AND SCHIZOPHRENIA IN TWINS

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.