Theory and Practice of Clinical Genomics

AH 5720  Theory and Practice of Clinical Genomics

Theory and practice of diagnostic laboratory methodologies and genomic data analyses for the clinical scientist. Sections are taught in a series of modules and include clinical case scenarios and analyses. With a change of content, this course may be repeated for credit.

Not all sections are offered each year.

Section 1: Focus On Microscopy

This modular laboratory will provide the learner with a strong skills base and knowledge of how the microscope works and the information to choose the appropriate microscopy technique, including basic and cutting-edge applications. Microscopy applications will include transmitted, phase-contrast, differential interference contrast, darkfield, epifluorescence, confocal, and two- and three-dimensional time-lapse microscopy will also be covered. Sessions will primarily be lecture and assignment-based with hands-on training in transmitted, phase-contrast and basic epifluorescence microscopy.

Section 2: In situ techniques

Application of in situ hybridization techniques to detect and localize sequences on chromosomes or tissue sections for the diagnosis of cytogenetic abnormalities, tumor biology, gene amplification and/or gene mapping. Topics include probe design, principles of hybridization, CGH, PRINS and immunocytochemistry.

Section 3: Genomics data in the clinical laboratory 

An introduction to bioinformatics for the design and/or analysis of diagnostic genetic tests. Topics covered include literature and protocol searches, primer design, probe selection, sequence and data analysis.  Databases examined will include Gene Tests, OMIM, Mitelman, CGAP, PubMed, NCBI, DAVID, UCSC genome browser, RepeatMasker/CENSOR, Ensembl, and others as appropriate.

Section 4: Chromosome analysis 1

The study of human chromosomes including banding, chromosome identification, polymorphic variation, structural and numerical abnormalities, determination of band level, and the International System for Human Cytogenetic Nomenclature.

Section 5: Chromosome analysis 2

Analysis of human, mouse and other model system organism karyotypes.  Pre-requisite:  Chromosome analysis 1.

Section 6:  DNA diagnostics

Practical experience with molecular techniques for the diagnosis of genetic disease. The student will perform genomic nucleic acid extraction, resolution and detection, analysis and characterization of nucleic acids, and nucleic acid amplification. Laboratory procedures will adhere to clinical laboratory quality control and assurance guidelines.

Section 7: Introduction to Cell Culture 

The course introduces students to the history, theory, and techniques of maintaining live cells in suspension and adherent culture. Main topics covered include safety considerations in cell culture, aseptic techniques, identification and eradication of culture infections, culture initiation, tissue dissociation methods, maintenance, subculture, and harvesting.  Cell viability, media design, cryopreservation and resuscitation of cells, as well as metaphase preparation, banding and chromosome analysis will also be highlighted.

Section 8: Microarray Cytogenetics 

The principles, protocols and interpretation of microarray data for cytogenetic analysis. Pre-requisite: familiarity with chromosomes/karyotyping or GPAH 5720 Section 4, or 5.

Section 9: Principles of Teratology

Principals of teratology and known teratogens presented through discussion and case reviews. Students will identify and appropriately use resources to identify teratogens, occupational exposure effects, and be provided with the skills to present data in plain language and supportive counseling with an appreciation for the psychological effects of exposure.

Section 10: Occupational Health and Safety in Laboratory Management  (2 credits)

This course aims to provide students with a practical knowledge of Occupational Safety and Health (OSH) laws in the USA and how they apply to the scientific community, with an emphasis on management of health and safety in laboratories.  Reference will be made to the Occupational Safety and Health Administration (OSHA) website for relevant reading materials throughout the course. Students will be provided with an introduction to safety and health in the workplace, the role of OSHA, risk management principals and general aspects of laboratory safety. This interactive class will provide students with practical experience in identifying hazards, assessing risks and learning how to select appropriate controls based on those risks.

Section 11: Next Generation Sequencing

The advent of Next Generation Sequencing (NGS) technologies has transformed how genetic research and clinical testing is being performed. Today, a human genome can today be sequenced in very short time for costs lower than ever expected allowing scientists and clinicians unprecedented possibilities for investigating human traits, mutations, and diseases. Students will generate a library, perform quantitative and quality analyses, and sequence using the Illumina platform. Students will be able to interpret results pre-and post-raw data processing as well as interpret, explain and report next-generation sequencing results for a clinical specimen in plain language, incorporating relevant sample information and patient phenotype.

Section 13: Cancer Panels and Tumor Profiling

Profiling somatic mutations of genes to inform about tumor evolution, prognostics and treatment as a tool in clinical oncology. In silico analysis of input candidates for panel design, evaluation of utility of commercially available cancer gene panels, and review of questions to consider when determining if genomic tumor testing is an appropriate method. Testing assessment will include sensitivity, sample requirements, limitations, panel types, and targeted versus genome profiling. Federal regulations, clinical actionability, as well as variant and tumor classifications will be reviewed.  Online and in-person weekend module training.

Instructor: Cara Statz, PhD, Clinical Analyst, Jackson Laboratory for Genomic Medicine.