1. THE ROLE OF NEXT GENERATION SEQUENCING IN CLINICAL PRACTICE
Prof. HATEM EL-SHANTI

2. NUCLEIC ACID STRUCTURE
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

3. DNA PROCESSING TRANSCRIPTION TRANSLATION
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

4. GENE STRUCTURE
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

5. DNA SEQUENCING
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

6. NEXT GENERATION SEQUENCING
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

7. BIOINFORMATIC TECHNOLOGY
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

8. BURDEN OF MENDELIAN DISORDERS
Birth defects include genetic disorders that are present at birth, such as metabolic disorders, as well as, congenital anomalies [>7,000]
About 6% of total births world-wide are born with a major birth defect of genetic etiology
Birth defects are commonly lethal
Survivors have a life-long disability
About half of those born with a major birth defect will die before their 5th birthday
About half of those born with a major birth defect who survive their 5th birthday will be disabled for life
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

9. CONVENTIONAL UNIVARIATE GENETIC TESTING
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

10. COMPREHENSIVE GENETIC TESTING
Gene or disease panels
Target (exons within genes and splice sites) enrichment
PCR based or Microarray based
Genes with one or overlapping phenotypes
Whole exome sequencing
Target (all possible exons and splice sites) enrichment
Phenotype driven analyses
Whole genome sequencing
Random shearing of the genome
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

11. NGS AND MENDELIAN DISEASE
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

12. NGS AND GENE DISCOVERY
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

13. CLINICAL APPLICATIONS
Gene or disease panels
Duchenne/Becker muscular dystrophy
Hearing loss
Neurodegenerative diseases / leukoencephalopathy
Early-onset neuromuscular diseases
Retinopathies
Whole exome sequencing
Mental retardation syndromes
Autism Spectrum Disorder (ASD)
Undetermined phenotype
Whole genome sequencing
Non-invasive prenatal diagnosis
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

14. BENEFITS Potential for reducing mortality and morbidity
Genetic counseling
Use of investigational drugs
Improving quality of life
Psychosocial benefits
Narrowing the differential diagnosis
Increased understanding of disease mechanisms
Improved variant database
Population-based screening
Lower average cost
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

15. Variants of unknown clinical significance
DRAWBACKS
Variants of unknown clinical significance
Incidental and unsolicited findings
Informational privacy and family relations
Commercial applications
Psychosocial drawbacks
Insufficient bioinformatic tools
Insufficient ethnic databases
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

16. LABORATORY AND CLINICAL STANDARDS
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

17. FIVE-TIER TERMINOLOGY SYSTEM
PATHOGENIC
LIKELY PATHOGENIC
UNCERTAIN CLINICAL SIGNIFICANCE
LIKELY BENIGN
BENIGN
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

18. NT5E mutations and arterial calcifications
GENOMIC MEDICINE
The influencing or basing the clinical care of a patient on the knowledge of the specific genomic variants the patient has
Whole Exome Sequencing in a child with intractable inflammatory bowel disease
NT5E mutations and arterial calcifications
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

19. PERSONALIZED MEDICINE
Advances the use of genomic medicine while shifting health care from being reactive to being predictive and preventive
Integrates unique clinico-pathological, genetic, genomic and environmental information to create an optimized care plan
Utilizes the molecular knowledge of common diseases to enhance prevention during wellness and begin therapy early
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

20. INTEGRATION INTO CLINICAL PRACTICE
Advance in genomic and computational technologies led to an exponential accumulation of genomic data
Exposure of the gaps in the infrastructure needed for the implementation of genomic data into clinical practice
Paucity of standardization into clinical tests
Physicians are unprepared to deliver the information
Deficiency in genetics knowledge amongst the average health-care provider
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018

21. THANK YOU FOR YOUR ATTENTION
Laboratory Medicine: Current Aspects and Future Prospects
6/5/2018