General Genetics Info

INTRODUCTION

Ampath Genetics is based at the National Reference Laboratory (NRL) in Centurion, Gauteng. We offer an extensive in-house complement of clinical and laboratory genetic services. The Ampath Genetics Laboratory is ISO 15189 and SANAS accredited, participates in several external quality assessments and is an HPCSA-approved training facility for Medical Scientists and Technologists.


Ampath Genetics is comprised of skilled and experienced HPCSA-registered Medical Scientists, Medical Technologists, Clinical Geneticists and Genetic Counsellors.


The department is divided into two areas, Clinical Genetics and Non-Clinical Genetics, where innovative techniques are utilised to assist in Clinical diagnostics as well as in Human Identification and Forensics, and this is a rapidly growing field.


The Ampath Genetics Laboratory offers a comprehensive range of genetic techniques, which allow interrogation of the genome from whole chromosomes down to single nucleotides of DNA. These techniques make use of advanced genetic technologies, including Next-Generation Sequencing (NGS). Both constitutional (germline) and somatic (tumour) diagnostic testing are available.

SERVICE OFFERING

Ampath Clinical Genetics offers tests that can be used for screening, diagnostic predictive, carrier, and prognostic purposes These include testing related to congenital abnormalities/developmental disorders, inherited cancer syndromes, reproductive genetics (non-invasive prenatal testing (NIPT), products of conception and prenatal diagnosis) paternity testing, pharmacogenomics and haematological/solid tumour testing.

INTERROGATING THE GENOME FROM THE LOWEST TO
THE HIGHEST RESOLUTION

LEVEL I: TRADITIONAL CYTOGENETICS (CHROMOSOMAL ANALYSIS)

Chromosomal analysis (karyotyping) represents one of the oldest investigative genetics approaches, offering a bird’s eye view of the genome at a low resolution. This hands-on technique requires significant expertise to analyse the chromosome complement of cultured cells in metaphase for large structural and/or numeric abnormalities. Depending on the indication, testing is performed on peripheral blood, bone marrow or amniocentesis samples.


LEVEL II: CYTOMOLECULAR GENETICS (FLUORESCENCE IN SITU HYBRIDISATION/FISH)

FISH offers a targeted approach to detecting specific chromosome abnormalities. FISH makes use of fluorescent probes, which bind to target regions on chromosomes, In order to determine the presence, absence and/or genomic location of these regions. Oncologists, haematologists and histopathologists are generally most knowledgeable about the various probe regions of interest for specific clinical situations, in their respective fields. Metaphase FISH analysis on cultured cells can be applied to elucidate a variety of cytogenetic findings, including microdeletions in developmental disorders and numerical/structural (including amplification events)associated with specific cancers.


LEVEL III: CYTOGENOMICS (ARRAY COMPARATIVE GENOME HYBRIDISATION/aCGH)

Array CGH is a molecular level investigation (not requiring light microscopic analysis as used for chromosomal analysis) which offers a genome-wide, high-resolution view of chromosomal copy number. The genomic regions analysed are smaller than those detectable by FISH analysis but still significantly larger than the resolution that can be studied when using sequencing technologies. Specialised software and databases are required to interpret the clinical significance of observed genetic variants. aCGH testing currently represents a first-tier investigative approach for children with unexplained neurodevelopmental delay, with or without dysmorphic features, and autism spectrum disorders.


LEVEL IV: MOLECULAR GENETICS

Molecular genetic testing utilises DNA technologies, including PCR and Sanger sequencing, to perform gene-level analyses. Such analyses attain resolution down to single nucleotides of DNA. The ability to identify specific mutations in specific genes can be of significant clinical value. Molecular genetic analyses also include screening for common aneuploidies, paternity/forensic testing, detection of common mutations in certain conditions, specific familial mutations, and detection of important tumour mutations which are used to diagnose or assist in determining the prognosis of the disease.


LEVEL V: NEXT-GENERATION SEQUENCING (NGS)

NGS is a high-throughput sequencing technique that is capable of generating vast amounts of genomic data. NGS can provide information on single base changes in DNA, chromosome copy number aberrations, and even gene expression alterations. Test designs and data analyses are performed by means of specialized software programmes, and a high level of skill is required to ascribe pathological significance to the findings. As a consequence, this testing modality demands increased input from Clinical Geneticists and Genetic Counsellors with regard to interpretation and conveying the information to individuals or families and their doctors. With an NGS approach, a number of genes can be incorporated in custom-designed panels required by pathologists or clinicians, allowing a single assay determination of clinically relevant genes/mutations for conditions including tumour diagnostics, inherited cancer syndromes and other phenotypes where one of numerous genes is implicated (genetic heterogeneity).


Whole exome and whole genome sequencing (WES/WGS) represent the next frontier in NGS application. Although not yet routinely diagnostically available at Ampath Genetics, WES involves sequencing of the protein coding regions of the DNA, offering a hypothesis-free approach to genetic diagnosis. WES/WGS poses data-handling and interpretive complexities, but is likely to provide answers to many diagnostic challenges.

GENETIC COUNSELLING AND CLINICAL GENETICS

Genetic counselling is a component of a holistic healthcare service. Genetic counselling is defined as "the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease" (Resta et al., 2006). The process aims to Integrate accurate patient/family histories, support In choosing the most appropriate genetic testing including information about costs and turnaround times, as well as consent discussions and post-test counselling regarding results, future options and familial implications.


These consultations are part of a multidisciplinary approach, where the Genetic Counsellor acts as facilitator of the various disciplines involvedtio that the patient can be offered a cohesive medical management plan. Genetic counselling is offered at the request of, and in collaboration with, the patient’s primary physician(s).


The Clinical Geneticist supports the Genetic Counsellor during some of the above processes, assists with suggesting or refining clinical diagnoses for a more focused and cost-effective laboratory testing approach, sometimes directs the investigative approach to be adopted in non-routine situations and, together with the Genetic Counsellor, is responsible for translating laboratory findings of assessed individuals or families into practical and actionable clinical report-findings.


To consult with a Genetic Counsellor or Clinical Geneticist, call Yolande Hollingworth, Genetics PA, at tel 012 678 0645 or e-mail <hollingworthy@ampath.co.za

Search

Genetics Sections