On The Spot e-News
Volume 4, Issue 7 | August 2009
In this issue:
- Signature Named to 2009 Inc. 5000
- Researchers at Signature Identify Likely Causative Gene for New Genetic Disorder
- Geneticists at Signature Associate Gene Deletion with Neurologic Anomalies
Signature Named to 2009 Inc. 5000 with Three-Year Sales Growth of 302.9%
Inc. magazine ranked Signature Genomic Laboratories no. 1012 on its third annual Inc. 5000, an exclusive ranking of the nation’s fastest-growing private companies. Signature experienced three-year sales growth of 302.9%, more than twice that of the Inc. 5000 industry median and over 12 times the industry benchmark. Signature was also ranked 70th of companies in the healthcare sector.
Commented Lisa G. Shaffer, Ph.D., President and CEO of Signature, "We are honored to be recognized for our well-planned strategic growth, which has continued despite the current economic conditions. I take special pride in the fact that, as we have grown, we have maintained our reputation for a high level of personal service and technical expertise."
The Inc. 5000 is ranked according to percentage revenue growth from 2005 through 2008. To qualify, companies must have been founded and generating revenue by the first week of 2005, and therefore able to show four full calendar years of sales. Additionally, they have to be U.S.-based, privately held, for profit, and independent—not subsidiaries or divisions of other companies—as of December 31, 2008. Revenue in 2005 must have been at least $200,000, and revenue in 2008 must have been at least $2 million. The top 10 percent of companies on the list comprise the Inc. 500, now in its 28th year.
Said Shaffer, "We are excited to have made the list two years in a row. Each year will be more difficult than the last, but to think that there are over 27 million businesses in the U.S. and that we are ranked 1012th among the fastest-growing private companies is astonishing to us."
Signature thanks its clients, without whom this award would not be possible.
Researchers at Signature Identify Likely Causative Gene for New Genetic Disorder
Two recent studies by geneticists at Signature demonstrate an important advantage of microarray analysis over conventional cytogenetic testing: the ability to detect small DNA imbalances that may reveal the causative genes for specific clinical features.
In the first study, researchers at Signature recently identified what is likely to be the causative gene for features of 2q32q33 microdeletion syndrome.
Individuals with the syndrome, which is caused by the loss of a small portion of DNA near the end of the long arm of chromosome 2, have severe mental retardation, growth retardation, unusual facial features, thin and sparse hair, feeding difficulties and cleft or high palate. Although deletions of varying amounts of DNA have been reported, the smallest region deleted in all patients contains at least seven genes. One of these genes, SATB2, is a DNA-binding protein that regulates how genes are expressed. The presence of only one copy of SATB2 , which occurs when one of the two copies normally present in humans has been deleted or mutated, has been suggested to cause the cleft or high palate of individuals with 2q32q33 microdeletion syndrome. In their study, the results of which were published online in the journal PloS ONE, researchers at Signature identified three individuals with small deletions of this region, all of which spanned part of SATB2 . After enrolling the patients in a study, review of clinical records showed similar clinical features among these individuals, including severe developmental delay, behavioral problems and tooth abnormalities. Interestingly, only one of the individuals had a cleft palate. Because the individuals had a portion of only one gene missing and the presence of many of the features associated with the larger microdeletion syndrome, the study authors suggested deletion of SATB2 was sufficient to cause several of the clinical features associated with 2q32q33 microdeletion syndrome.
"These results are exciting because they demonstrate microarray analysis can help identify the cause of some clinical features associated with genetic disorders. Identifying the causative gene, in some cases, may lead to treatment targets in the future," said Dr. Lisa G. Shaffer, Ph.D., senior author of the study. "These results are particularly important for syndromes that have only been identified in a small number of individuals, because they allow us to define the clinical spectrum of the syndrome better."
Added Dr. Shaffer, "the identification of such small abnormalities in these patients also demonstrates that, for diagnostic purposes, it is imprudent to assume that DNA gains and losses under a certain size are not clinically relevant to the patient’s features. Some laboratories use an arbitrary cutoff for alteration sizes to decide clinical relevance. We have many examples in GCAD , our proprietary database of alterations identified at our laboratory, of small alterations we deemed clinically relevant after comparison to other cases in the database and scientific literature. GCAD was developed after testing more than 40,000 patients and contains over 8,000 diagnoses. We are committed to publishing unique cases to aid other laboratories in the use of microarrays."
Geneticists at Signature Associate Gene Deletion with Neurologic Anomalies
In the second study, geneticists at Signature recently associated absence of a gene on chromosome 6 with neurologic anomalies including developmental delay.
In the study, published in the journal Molecular Cytogenetics, Signature identified a missing, or deleted, segment of DNA on one copy of chromosome 6 in a male with small stature, developmental delay, ear malformations and a brain MRI showing a decrease in the number of cells that transmit information within the brain. Within the missing region of DNA lay only two genes. Although one gene may play a role in tumor suppression and is unlikely to be associated with the patient’s clinical features, the other gene, EPHA7 , is an intriguing candidate; previous studies of the homologous gene in mice have shown it functions during formation and development of the mouse embryo to determine brain size and shape and aid in the development of the central nervous system. Furthermore, similar features, including neurodevelopmental anomalies, growth retardation and ear malformations, in individuals with deletions of larger segments of DNA that overlap the one missing in their patient prompted the geneticists at Signature to suggest EPHA7 is crucial for, among other processes, proper neurological development.
Commented Dr. Blake C. Ballif, Ph.D., Director of Product Development and Research at Signature and senior author of the study, "Although individuals with deletions of this region on chromosome 6 have been identified before, most of these deletions removed or disrupted many genes; consequently, it was impossible to know the clinical consequences of deletion of any one gene. Our results are exciting because they demonstrate that, because microarray analysis can identify very small DNA imbalances, it has the potential to identify the causative genes of genetic diseases, which can can aid prognosis and may lead to the development of targeted treatments."