Description: The Division of Genetic Diagnostics (GnDx) provides cytogenomic microarray analysis for both clinical and research purposes. The current platform that is being utilized is a 135,000 oligonucleotide microarray for an average genomic coverage of 35 kb. Custom array analysis can also be provided, following consultation with the laboratory director. We are located on the North Campus in room NA2.508.
Director: Kathleen S. Wilson, M.D., FCAP, FACMG
McDermott Center for Human Growth and Development
UT Southwestern Medical Center at Dallas
6000 Harry Hines Blvd.
Hamon Building, Room NA2.508
Dallas, Texas 75390-8591
Division of Genetic Diagnostics
General Laboratory Number: (214) 648-1154
Fax: (214) 648-5509
Dr. Kathleen Wilson:
Phone: (214) 648-7404
Research: $1250 per specimen
Clinical: Contact Laboratory Director
Cytogenomic Microarray Analysis Requirements
Cytogenomic microarray analysis is a high resolution chromosomal analysis with both research and clinical applications. It is based on the technology of array Comparative Genomic Hybridization (aCGH) for the purpose of detecting clinically significant copy number changes throughout the entire genome. This whole genome scan offers a much higher level of resolution (35 kilobases) when compared with other cytogenetic technologies: conventional cytogenetic analysis (karyotyping, 3-4 megabases) and the targeted technique of fluorescence in situ hybridization (FISH, 300-400 kilobases). It is in wide clinical use in the postnatal population and clinical trials of its use in prenatal settings are currently in progress through the National Institutes of Health (NIH). In patients with mental retardation and developmental delay, this technology greatly improves the diagnostic yield of classical conventional cytogenetic analysis and allows for the simultaneous evaluation of hundreds of loci for the detection of many microdeletion and microduplication disorders. For example, conventional cytogenetic analysis detects cytogenetic abnormalities in about 4% of children with global developmental delay while microarray analysis detects chromosome abnormalities in up to ~20% of patients. In addition, nearly 10% of individuals with autism spectrum disorders have any of a large number of copy number variations as the underlying etiology of their condition. The increased detection rate of chromosome abnormalities with this higher resolution, cutting-edge technology not only improves patient care but is cost effective. Once the patient receives a definitive genetic diagnosis no additional testing is necessitated, and key family members also at risk can be identified and evaluated with the established genetic aberration also obviating the need for additional costly genetic testing.
The interpretation and subsequent reporting is also distinct from any other type of genetic diagnostic interpretation. Since this technology interrogates the entire human genome at a high resolution for copy number gains and losses, it requires transparent computer algorithms designed to accommodate large sets of comparative data for generation of results that are subsequently interpreted by a qualified professional. Extensive clinical correlation is part of the interpretation utilizing copy number variation (CNV) databases to determine what is clinically significant and what is considered normal population variation (not clinically significant). Additionally, any presumed abnormality is also required to be confirmed (whenever possible) with another established genetic modality such as fluorescence in situ hybridization (FISH).
The Division of Genetic Diagnostics is utilizing a custom designed microarray for clinical cytogenomic diagnostics. It was designed and developed by cytogeneticists for both research and clinical applications. The 135,000 oligonucleotides on this microarray cover every region known to be involved in cytogenetic abnormalities, including over 200 syndromes, the pericentromeric regions, and subtelomeres. It has a maximum probe spacing of one probe every 35 kb throughout the genome and one probe every 10 kb in clinical regions. The microarray has been customized for increased coverage in regions associated with seizure disorders both canonical epilepsy genes and genes associated with disorders that can present with epilepsy, significantly improving the detection rate for these disorders in the pediatric neurologic population. The high level of resolution and degree of additional customization for clinically significant regions including those with seizure disorders, are features that make this microarray platform distinct.
Customized microarrays can also be developed for various research purposes. The laboratory director is available to discuss with investigators what their specifications and needs are.
Interpretation of microarray results requires accurate correlation with databases that contain established chromosome aberrations (clinically significant) and normal copy number variations (not clinically significant). Genetic Diagnostics will be evaluating cytogenomic microarray patient results using software that correlates individual patient results with a database that contains over 50,000 patient cases as well as over 200 regions of syndromic coverage, and over 80 regions of normal population variation. The ability to distinguish clinically insignificant copy number variations from those genetic changes that are clinically significant through utilization of this database, reduces patient cost by preventing unnecessary testing of other family members or additional testing of the patient.
Online ordering/reporting and internal systems
The Laboratory Information System (LIS) for the Division of Genetic Diagnostics is the WindoPath/Outreach product of Psyche Systems Corporation which provides online ordering and reporting. The system notifies Genetic Diagnostics as soon as an order is placed allowing for each specimen to be tracked, thus preventing loss or delay in transit and subsequent specimen compromise. Final reports are immediately posted to the HIPAA compliant web portal following sign out, thus decreasing reporting delays due to traditional mail or faxing and also maintaining a high degree of security. Authorized users can also retrieve patient results 24/7 from any location that has internet access. Other key components in the software that allow for a high level of functionality and efficiency within the laboratory include electronic transmission and retention of data, bar-coding capabilities for tracking of specimens, electronic storage of PHI, electronic inventory control, quality assurance and quality control and a flexible format for generating client billing statements.
Availability of expert consultation
The Genetic Diagnostics Laboratory Director and staff are available to communicate and assist in problem solving for all aspects of the diagnostic or research process. The Laboratory Director views the consultative role as critical to achieving the highest result quality.