On The Spot e-News
Volume 6, Issue 7 | August 2011
In this issue:
- Signature Genomics helps to develop a copy number variation morbidity map
of developmental delay - Genetic changes in schizophrenia have broader disease implications
- Join us for Sessions at the ISUOG World Congress 2011
Signature Genomics helps to develop a copy number variation morbidity map of developmental delay
Signature Genomics collaborates with the University of Washington on the analysis of results from more than 15,000 clinical microarray studies.
While the use of molecular cytogenetic technologies to detect DNA copy number variations (CNVs) continues to become more widespread in the testing of children and adults with a spectrum of neurodevelopmental disease, the interpretation of some of the CNVs found through this testing remains difficult. Certain CNVs can be found in healthy individuals, affected individuals, and in parents of affected individuals. And in some cases, it can be unclear if these CNVs are contributing to disease development. To understand the contribution of these CNVs to disease, large numbers of patients and healthy control individuals need to be analyzed and compared. Until now data from large enough groups has been hard to find or unavailable.
In partnership with Dr. Evan E. Eichler's lab at the University of Washington, researchers at Signature Genomics have co-authored an article, released this month online ahead-of-print by Nature Genetics, that compared CNV data from 15,767 patients studied at Signature to CNV data from 8,329 healthy controls studied at Dr. Eichler's lab.
This productive collaboration has resulted in the identification of 59 disease-causing CNVs, including 14 that are newly reported in the literature or for which significance in disease was previously unclear. One such CNV is a recurrent 15q25 microdeletion, found in five individuals affected with developmental delay and other neurologic features. Analysis of this data also helped to narrow regions of the genome likely responsible for previously described genetic disorders, such as the 17q21.31 microdeletion syndrome.
Additional in-depth analysis of the data by the Eichler lab has allowed for further conclusions to be drawn. Approximately 14.2% of developmental disabilities in these patients are caused by CNVs that are at least 400 kb in size. And this research has generated a list of 940 candidate genes that may be disease-causing when included in a CNV. While these genes are still only candidates, this list will be useful for future research into the various diseases associated with these CNVs.
"Microarray technology has greatly increased our understanding of the genetic causes of developmental delay and other disorders over the past seven years, but it has also uncovered further unanswered questions," said Lisa G. Shaffer, Ph.D., Chief Scientific Officer of Molecular Diagnostics, PerkinElmer and co-founder of Signature Genomic Laboratories. "Data mining of such large datasets, such as the one at Signature, will help further our understanding of the genetics of developmental disorders."
Genetic changes in schizophrenia have broader disease implications
Signature Genomics identifies copy number variations previously associated with schizophrenia in individuals with autism, developmental delays, or intellectual disabilities.
While schizophrenia has long been recognized as a disease in which genetic predisposition plays a role, specific genetic causes of the disease have mostly remained elusive. Recent studies have been able to identify likely causative DNA copy-number variations (CNVs) in some individuals with schizophrenia. Additionally, some of those CNVs have been previously implicated in other diseases, such as autism or developmental delays, suggesting that genetic predisposition to these diseases may be related.
To further understand if CNVs identified in schizophrenia may cause other disease, researchers at Signature Genomics searched for similar CNVs among 38,779 patients referred for clinical microarray testing. Within this patient population, they identified 1150 individuals with CNVs that have been identified in schizophrenia. These individuals had a range of other developmental and neurological disabilities, including developmental delay, intellectual disability, autism-related disorders, and birth defects.
The results of this study, published online ahead-of-print by Genetics in Medicine, show that genetic causes of schizophrenia can also cause a variety of diseases, including pediatric developmental disorders. These CNVs may generally impair brain development, and this may ultimately lead to schizophrenia in some individuals, while others may develop autism, behavior problems, or developmental delay. Also, healthy parents may carry some of these CNVs, which may only be one of multiple factors, both genetic and environmental, that collectively cause a specific disease. Researchers caution suggesting that any specific CNV is associated with only schizophrenia or any other specific neurodevelopmental condition.
"We are solidifying our assumptions that microarray technology is a useful diagnostic tool in a broad range of patient populations," said Lisa G. Shaffer, Ph.D., Chief Scientific Officer of Molecular Diagnostics, PerkinElmer and co-founder of Signature Genomic Laboratories. "The finding of the same copy number alterations in schizophrenia and other developmental disorders is providing more information regarding the molecular basis of such conditions."
Visit Signature Genomics and PerkinElmer
at the International Society of Ultrasound in Obstetrics
and Gynecology (ISUOG) World Congress 2011
ISUOG World Congress
September 18–22, 2011
Los Angeles, California
Please visit us at booth #29.
Please join us for the following sessions:
- State of the Art Session:
The use of microarrays in pregnancies with abnormal ultrasound findings
Lisa G. Shaffer, PhD; Chief Scientific Officer, Molecular Diagnostics, PerkinElmer - Tue, Sep 20 - 8:00 AM
- Chair 1: Lawrence D. Platt
- Location: LA Room
- Workshop:
Advanced methods in prenatal diagnosis
Molecular cytogenetic approaches for identifying chromosome abnormalities in prenatal testing
Lisa G. Shaffer, PhD; Chief Scientific Officer, Molecular Diagnostics, PerkinElmer - Tue, Sep 20 - 4:00 PM
- Chair 1: Lawrence D. Platt
- Location: Constellation