John Sterling Editor in Chief Genetic Engineering & Biotechnology News

South Carolina Institute Offers a Wide Range of Clinical Services

In October, the South Carolina-based Greenwood Genetic Center (GGC) launched a whole exome sequencing (WES) program. The technique, carried out via next-generation sequencing, is particularly appropriate for patients who need additional genetic testing, e.g., chromosome analysis and single gene sequencing, beyond traditional approaches. Bioinformatics specialists analyze the results to help narrow down the hundreds or thousands of gene variants, hoping that a single mutation can explain a patient’s condition.

A group led by Charles E. Schwartz, Ph.D., director of research and head of GGC’s JC Self Research Institute, has been investigating genes associated with autosomal forms of intellectual disability (ID) and autism, utilizing clinical material available at GGC. Dr. Schwartz’s team identified an autosomal recessive mutation in the ST3GAL5 gene using WES. The gene codes for a critical enzyme in the ganglioside biosynthetic pathway and the missense mutation results in a total absence of the GM3 ganglioside and a neurological disorder known as neurocutaneous melanosis.

“We plan to apply whole exome sequencing in additional families with ID or autism in the hope of identifying novel genetic alterations responsible for various phenotypes,” said Dr. Schwartz, who is also senior research scientist and director of the Center for Molecular Studies.

The GGC was founded in 1974 as a nonprofit institute to serve South Carolina and organized to provide clinical genetic services, diagnostic laboratory testing, educational programs, and research in the field of medical genetics. WES is one of a number of techniques offered by GGC’s diagnostic labs, which specialize in biochemical, cytogenetic, and molecular genetic testing.

Greenwood Genetic Center

GGC’s Biochemical Laboratory provides diagnostic and screening tests for a variety of inherited metabolic disorders. Analyte and enzyme testing is available for disorders including lysosomal storage diseases, congenital disorders of glycosylation, mucolipidoses, and numerous inborn errors of metabolism.

The Cytogenetics Laboratory focuses on constitutional chromosomal aberrations as well as abnormalities related to hematological malignancies. Routine and high-resolution karyotyping, FISH, array CGH, and whole genome SNP arrays are available to diagnose a suspected chromosomal abnormality in blood, solid tissue, or prenatal samples. Cytogenetic analysis of malignancies include chromosome studies and numerous available FISH probes to provide information regarding hematological prognosis and treatment strategies.

The Molecular Diagnostic Laboratory carries out DNA analysis for many genetic disorders via gene sequencing, targeted mutation analysis, multiplex ligation-dependent probe amplification deletion/duplication testing, trinucleotide repeat analysis, and next-generation sequencing. Testing is available for both common and rare genetic disorders with a special interest in conditions involving X-linked intellectual disability. Prenatal diagnosis is also available for many of these disorders.

“We use cutting-edge technologies to assist clinicians in making an accurate and thorough diagnosis, helping both the patients and their families better understand the cause of the disorder and furthering the path toward treatments and cures,” Alka Chaubey, Ph.D., director of the cytogenetics laboratory, told Clinical OMICs. “The close relationship between the GGC’s molecular diagnostic laboratory and research division allows for a smooth transition from scientific discovery to diagnostic testing.”

According to Dr. Chaubey, research at the JC Self Institute is divided into two major centers. The primary research focus in the Center for Molecular Studies is gaining a greater understanding of intellectual disability, discovering new mechanisms that contribute to genetic disease, and developing new strategies for prevention. The Center for Anatomic Studies devotes its resources toward understanding the mechanisms by which birth defects occur and how they may be prevented.

Roger E. Stevenson, M.D., senior clinical geneticist, points out that the application of the new genomic technologies has dramatically changed the era of diagnostic genetics. “With these technological tools, our clinicians can realistically anticipate finding the specific cause of genetic disabilities and related disorders in their patients and can convey hope to the family,” he explained. “With specific genetic diagnoses, the clinical team can provide recurrence risks for the family (or assurance that there is no risk of recurrence), supply information on the natural history of the disorder, attend to the indicated management issues, conduct carrier testing and prenatal diagnosis, and consider therapeutic strategies.”

Bridging Lab and Clinical Activities

Dr. Stevenson added that the new technologies have also led to an increased appreciation for the occurrence and frequency of de novo mutations, the role of somatic mosaicism in human disease and malformations, and the complexity of epigenetic mechanisms that can alter gene expression.

“While the relationship between the clinic and the diagnostic genetics laboratory has always been close, the new technologies have brought them even closer,” he said. “The communication between them has become essential for the expedient and correct interpretation of laboratory findings.”

Dr. Stevenson predicts that the single most important change that will occur at the GGC within the next five years will be the full transition from the age of diagnostic genetics to the era of therapeutic genetics.
In addition to next-gen sequencing, the GGC also relies on microarrays for much of its work. The center has partnered with Affymetrix on a number of projects. Four years ago, the GGC started running the Affymetrix legacy SNP 6.0 array platform that had 1.8 million probes. In 2012, the center transitioned to the CytoScan HD array (2.7 million probes).

“We were one of Affymetrix’s three FDA clinical sites for their site-to-site reproducibility study and played key roles in 4 of the 10 clinical trials,” noted Dr. Chaubey. “Affymetrix obtained FDA clearance for the CytoScan Dx Assay earlier this year and in September GGC became the first site to launch the DX assay.”

“The sea change in technologies has allowed us to better understand the biologic bases for hereditary disease, and that understanding in turn leads to the most important advances of all—cure or substantial amelioration of the adverse signs, symptoms, and complications caused by these diseases,” she explained.

Since 2002, when the GGC faculty held a retreat to explore the possibilities of treatment of genetic disorders, there has been a steady movement toward treatment, involving a change in the mindset of the entire faculty, monthly faculty updates on new/different approaches to treatment, and an active task force on treatment “to keep us on focus,” according to Steven Skinner, M.D., director of the GGC.

He notes that a major new facility—The South Carolina Center of Treatment of Genetic Disorders—has been constructed on the GGC campus to give visible evidence of this philosophical change and commitment. The structure of the GGC’s treatment initiative has been subdivided into activities in five core areas: metabolic disease, enzyme replacement, birth defect treatment/prevention, epigenetics, and novel therapies.

“None of this means that we are abandoning diagnostic genetics but rather that we are capitalizing on the potential that diagnostics genetics offers and which may help us treat human diseases much more effectively,” said Dr. Skinner. 

John Sterling is editor in chief of Genetic Engineering & Biotechnology News. ([email protected])

This article was originally published in the February 2015 issue of Clinical OMICs. For more content like this and details on how to get a free subscription to this digital publication, go to

Previous articleFDA Commissioner Hamburg Stepping Down
Next articleCRISPR Gene Editing Improved with Small Molecule Introduction