BOSTON, MA—When chromosomes replicate, sometimes there is an exchange of genetic material within a chromosome or between two or more chromosomes without a significant loss of genetic material. This exchange, known as a balanced chromosomal abnormality (BCA), can cause rearrangements in the genetic code.
Researchers from 15 institutions in three countries including Brigham and Women's Hospital (BWH), Massachusetts General Hospital, Harvard Medical School, and the Broad Institute found that due to these rearrangements, BCAs harbor a reservoir of disruptions in the code that could lead to autism and other neurodevelopmental disorders. The researchers also uncovered 22 new genes that may contribute to or increase the risk of autism or abnormal neurodevelopment.
The study will be published in the print issue of Cell on April 27, 2012.
The researchers used a strategy that involved directly sequencing BCAs to reveal genes at the breakpoints and show that these genes are related to autism and other neurodevelopmental disorders.
This study is part of a larger, ongoing collaborative endeavor, the Developmental Genome Anatomy Project (DGAP), to identify genes critical in human development.
The researchers discovered that the genetic code can be disrupted at various distinct sites and still result in autism. The disruptions occur in several different groups of genes, including those already individually suspected to be associated with abnormal neurodevelopment; those which illuminate a single gene as important in large regions previously defined as genomic disorders; as well as those associated with psychiatric disorders that can have much later onset than neurodevelopmental disorders.
"BCAs provide a unique opportunity to pinpoint a gene and validate it in a disorder," said Cynthia Morton, PhD, BWH director of cytogenetics, and principal investigator of DGAP. "These discoveries can illuminate biological pathways that may be a window to a new therapy. We are all grateful to the individuals and their families who make these fundamental findings possible through their participation as subjects in these studies."
This research was supported by the Simons Foundation Autism Research Initiative; Autism Speaks; Massachusetts General Hospital ECOR Fund for Medical Discovery Award; and the National Institutes of Health (NIH) and Human Services including the National Institute of General Medical Sciences, the National Institute of Mental Health and the National Human Genome Research Institute. NIH and NIMH grants included P01-GM061354, R21-HD065286 and F32-MH087123.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. BWH is the home of the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), www.brighamandwomens.org/research, BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 900 physician-investigators and renowned biomedical scientists and faculty supported by more than $537 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit www.brighamandwomens.org.
Journal
Cell