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


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.