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The Application of Validation and Proficiency Testing Concepts From Current Clinical Genetic Diagnostics
For the Implementation of New Genetic Technologies
Genomics 2015Kathleen S. Wilson, M.D.
The University of Texas Southwestern Medical Center
Advent of new genetic technologies utilized for clinical diagnostics is rapid.
Advent of new genetic technologies utilized for clinical diagnostics is rapid.
Implementation of these evolving technologies is challenging.
Next Generation SequencingMultiple, fragmented sequence reads assembled based on overlapping areas
https://en.wikipedia.org/wiki/DNA_sequencing
Whole Exome Sequencing
https://en.wikipedia.org/wiki/Exome_sequencing#/media/File:Exome_Sequencing_Workflow_1a.png
College of American Pathologists/American College of Medical Genetics Cytogenetics Resource Committee
College of American Pathologists/American College of Medical Genetics Cytogenetics Resource Committee
Fluorescence in situ hybridization (FISH)
College of American Pathologists/American College of Medical Genetics Cytogenetics Resource Committee
Fluorescence in situ hybridization (FISH)
Cytogenomic microarray analysis (CMA)
College of American Pathologists/American College of Medical Genetics Cytogenetics Resource Committee
Fluorescence in situ hybridization (FISH)
Cytogenomic microarray analysis (CMA)
Relevance for the rapidly evolving sequencing technologies
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
UTSW FISH Probe Validation
UTSW FISH Probe Validation
1. Metaphase probesa. Unique sequence
1. Localization2. Analytical validation
b. Repeat sequence/whole chromosome paints1. Localization2. Analytical validation
2. Interphase probes (unique sequence and repeat sequence only)a. Localizationb. Analytical validation
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
Smear preparationsDropped cell suspensions from culturesMonolayer culturesUncultured amniocytesCytospin preparationsTouch preparationsFFPE (formalyn fixed parraffin embedded tissues) (CYJ/K/L)Urine
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
BCR/ABL1RUNX1T1/RUNX1PML/RARAMicrodeletion cocktails
ETC…
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
Dropped cell suspensions from cultures (CYF)Urine (Urovysion) (CYI)FFPE (formalyn fixed parraffin embedded tissues) (CYJ/K/L)HER2 (CYH)
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
Dropped cell suspensions from cultures (CYF)Urine (Urovysion) (CYI)
Cytogenomic Microarray Analysis
This was the fifteenth CAP/ACMG Survey mailing for whole genome copy number changes by microarray technology. This was the eleventh GRADED CYCGH Survey. The number of participants enrolled in this Survey has been 27, 34, 50, 63, 72, 80, 92, 96, 123, 124, 144, 147, 158, 161, and 170 in the first through fifteenth Surveys, respectively. CYCGH-01 and CYCGH-02 reached participant consensus of greater than 80% and were graded.
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
2. Vendor provided Quality Control measures as part of assay development and validation
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
2. Vendor provided Quality Control measures as part of assay development and validation
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
2. Vendor provided Quality Control measures as part of assay development and validation
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
2. Vendor provided Quality Control measures as part of assay development and validation
3. DNA quality
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
2. Vendor provided Quality Control measures as part of assay development and validation
3. DNA quality
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
2. Vendor provided Quality Control measures as part of assay development and validation
3. DNA quality
4. Computer technology
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
2. Vendor provided Quality Control measures as part of assay development and validation
3. DNA quality
4. Computer technology-interface checks
Lessons learned from prior technology have relevance for the clinical genetic diagnostics of the future.
1. Method not analyte based
2. Vendor provided Quality Control measures as part of assay development and validation
3. DNA quality
4. Computer technology-interface checks
5. Scope of validation
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