WHAT
DOES DISEASE DISCORDANCE MEAN IN MONOZYGOTIC TWINS?
Cassandra L.
Smith*, Giang Nguyen, Niels Storm, and Joe Bouchard. Center for
Advanced Biotechnology and Departments of Biotechnology, Biology
and Pharmacology, Boston University, Boston MA
Concordance studies in
monozygotic and dizygotic twins have been used to determine
genetic and environmental contributors to disease phenotypes.
These studies assume that monozygotic twins have identical
genomes. These assumptions fail to take into account epigenetic
and somatic DNA changes that may produce discordance in disease
phenotype.
We have developed a targeted
genomic differential display (TGDD) method that allows us to
quantitate the level of genome identity between individuals and
in different tissues. Genomic targeting reduces genome complexity
and focuses analysis on and nearby DNA sequence families.
The level of genome identity
varies in different twin pairs. Studies are underway to determine
the source of variation. The level of genome identity is very
high. Despite this, several specific differences were identified
and characterized in detail. One difference represents a series
of multiple single base changes while another represents a de
novo recombination event. These and other genomic changes are
being characterized in Schizophrenic and normal twins and other
samples of ill and well individuals.