Genomes of identical twins reveal epigenetic changes that may play ...

Genomes of identical twins reveal epigenetic changes that may play role in lupus
December 22, 2009 – Identical twins look the same and are nearly genetically
identical, but environmental factors and the resulting cellular changes could
cause disease in one sibling and not the other. In a study published online in
Genome Research (www.genome.org), scientists have studied twins discordant for
the autoimmune disease lupus, mapping DNA modifications across the genome and
shedding light on epigenetic changes that may play a role in the disease.
Because the genetic makeup of monozygotic twins (commonly known as identical twins)
is nearly identical, phenotypic traits and heritable diseases are often concordant,
manifesting in both siblings. However, some phenotypes and diseases such as autoimmune
disease can arise in only one sibling, suggesting other factors such as environment
likely play a role in determining phenotypic differences.
Epigenetic modifications, cellular changes that can influence expression of genes,
are now widely recognized to influence phenotype and frequently occur in disease.
Furthermore, environmental factors such as diet and chemical exposure can change
the epigenetic status of genes. Recent research has identified epigenetic modifications
at several aberrantly regulated genes in autoimmune diseases such as systemic
lupus erythematosus (SLE), and other studies have suggested that epigenetic differences
are associated with phenotypic discordance between identical twins.
In this work, researchers from Spain and the United States performed the first
genome-wide high-throughput analysis of a specific epigenetic modification, DNA
methylation, in the context of autoimmune disease. Taking advantage of the identical
genetic background in monozygotic twins, the group directly compared DNA methylation
in healthy twins and twins discordant for autoimmune diseases, including SLE,
looking for changes that could be related to pathogenesis in one sibling and not
the other.
In the case of SLE, the group found widespread changes in DNA methylation status
at a significant number of genes. Dr. Esteban Ballestar, senior author of the
study, noted that this is the largest number of genes exhibiting DNA methylation
changes observed in an autoimmune disease to date, and includes genes previously
implicated in SLE pathogenesis. Importantly, Ballestar’s team found that
a significant number of the novel differentially methylated genes are related
to multiple immune system functions and are potentially linked to SLE.
“Our study suggests that the effect of the environment or differences in
lifestyle may leave a molecular mark in key genes for immune function that contributes
to the differential onset of the disease in twins,” Ballestar said. Most
studies of DNA methylation and human disease have been in the context of cancer
research, Ballestar noted, and he hopes that this work will attract more researchers
to also investigate DNA methylation alterations in autoimmune disease and other
disorders for the development of therapies.Scientists from Bellvitge Biomedical
Research Institute (Barcelona, Spain), Christian-Albrechts-University Kiel (Kiel,
Germany), Centro de Investigacion Principe Felipe (Valencia, Spain), the Broad
Institute of MIT and Harvard (Cambridge, MA), Brigham and Women’s Hospital
(Brookline, MA), the National Institute of Environmental Health Sciences (Bethesda,
MD), Gregorio Marañon Hospital (Madrid, Spain), ISCIII Center for Biomedical
Research on Rare Diseases (Valencia, Spain), Institut de Medicina Predictiva i
Personalitzada del Càncer (Badalona, Spain), and the University of Oklahoma
Health Sciences Center (Oklahoma City, OK) contributed to this study.
This work was supported by the Spanish Ministry of Science and Innovation, the
National Institute of Environmental Health Sciences, the National Institutes of
Health, the Alliance for Lupus Research, the US Department of Veterans Affairs,
and a BEFI Predoctoral Fellowship from the Carlos III Health Institute, Spain.
About Genome Research:
Launched in 1995, Genome Research (www.genome.org) is an international, continuously
published, peer-reviewed journal that focuses on research that provides novel
insights into the genome biology of all organisms, including advances in genomic
medicine. Among the topics considered by the journal are genome structure and
function, comparative genomics, molecular evolution, genome-scale quantitative
and population genetics, proteomics, epigenomics, and systems biology. The journal
also features exciting gene discoveries and reports of cutting-edge computational
biology and high-throughput methodologies.
About Cold Spring Harbor Laboratory Press:
Cold Spring Harbor Laboratory is a private, nonprofit institution in New York
that conducts research in cancer and other life sciences and has a variety of
educational programs. Its Press, originating in 1933, is the largest of the Laboratory's
five education divisions and is a publisher of books, journals, and electronic
media for scientists, students, and the general public.
Genome Research issues press releases to highlight significant research studies
that are published in the journal.