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Introduction to: MOLECULAR DIAGNOSTICS Past, Present and Future Omer Yahia M.Sc. Molecular medicine
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Introduction to:
MOLECULAR DIAGNOSTICS
Past, Present and Future
Omer Yahia
M.Sc. Molecular medicine
Content:
• Molecular medicine.
• Genetic diseases VS environmental diseases
• Development of diagnosis.
• Molecular diagnostics.
• Role of molecular diagnostic through out life.
• Areas of molecular diagnostics.
• Drug selection in cancer.
Molecular medicineThe application of molecular biology to medicine.
• Molecular biology applications are
Genetics Genomics Proteomics
The study of the form, function and interactions of the proteins of an organism.
Deals with the laws of inheritance and the properties of genes.
The study of the form, function and interactions of the genes of an organism.
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It is a field of applied sciences, that deals with the molecular basis of diseases, or in other words the molecular mechanisms underlying health problem that characterize the type of diagnosis and treatment. it is deffer from that symptomatic medicine in which doctors respond to fever, joint pain and anemia by pain killer and anti-pyratics in place of asking about patient history and ordering a request to check for sickle cell anemia for example
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Mendel's Laws: (1) principle of segregation: each member of chromosome pair separate from each other during gamete formation. (2) principle of independent assortment: each pair of chromosome assort independently of the another pair of chromosome during the production of gametes we have two important terms in pedigrees; genotype and phenotype. the genotypes: is a list of the alleles present at one or a number of loci Phenotype: is the observable properties of an organism A locus: (plural loci) is a unique chromosomal location defining the position of an individual gene or DNA sequence Alleles: are alternative versions of a gene. For example, A, B, and 0 are alternative alleles at the ABO locus
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while pedigrees make use of Mendelian disorders (either autosomal dominant, autosomal recessive and X-linked diseases) which are build on SNP , the genomics and proteomics are deal with multi factorial diseases that are affected by many genes many traits don't fall into discrete categories ( e.g. height for example theses are called quantitative trait) quantitative trait may follow Mendelian patterns of inheritance or may deviate from it (called complex trait e.g. Cancer , Diabetes ...etc ) they can be further studied by genome wide scan and candidate gene studies.
Genetic Diseases VS environmental diseases
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Mendelian disorders (in the aggregate) are present in ~2-3% of all newborns, although disease may not be manifest for years to decades, if ever! Simple” Mendelian Disorders are not so simple because of *New Mutation *Mosaicism – The exception to every cell having the same DNA *Decreased Penetrance – Disease genotype without phenotype *co-dominance: Disease in Carriers of Recessive Disorders – Not always “silent”
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Infectious diseases can be a genetic disease when the individual become more susceptible for certain infectious agent due to mutation in genes control immune system and/or structural protective layers or defective lymphoid organs. e.g..adenosin deaminase deficiency This autosomal recessive deficiency causes a type of severe combined immunodeficiency (SCID),involving T-cell, B-cell and NK-cell depletion (lymphocytopenia).
Genetic diseases
Aneuploidy SNP Cancer isa complex disease
Genetic + environmental
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genetic diseases are ranged from single nucleotide polymorphism(SNP) to addition of complete chromosome (e.g. aneuploidy in down syndrome) however, it can manifested it self by more than one tumor suppressor and oncogene as in colorectal cancer.
How gene mutation cause disease
Eye Observation light Microscopic observation Electron microscopic observation molecular diagnostic
Development of Diagnostics
J. Herrick 1910. Rudolf Virchow (1821–1902)
Giovanni Battista Morgagni(1682–1771)
Hans Busch (1926)
Vernon Ingram 1950
AmpliChip CYP450 test 2003
Z
O
O
M
Main events affect
Molecular diagnostics
Molecular Diagnostics:
Is a technique used to analyze biological markers in the genome
and proteome by applying molecular biology to medical testing
Pre-natal testing
Disease predisposition
Disease detection
Drug selection
Recurrence monitoring
Key questions
-> Need for Molecular tests
“Is the baby
healthy? ““What diseases
is this patient at
risk for?”
“Has this
patient a
disease?”
“What drugs
should I
prescribe?”
“How has the
disease
returned?”
Role of molecular diagnostics through out the life
Angelina
Jolie
HIV viral load
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This group range from day zero to the 20th week of gestation. We can do either carrier screening according the the common RACE associated diseases (high cost)or selectively do test for the highly under-risk families according to family history. Test result lead to a decision either to terminate gestation or not which is associated with many ethical,religious, and tradition issues. In best situation the patient referred to clinic to do gene therapy. e.g. sickle cell anemia , thalacemia and cystic fibrosis
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Angelina Joli is a famous Hollywood actress but now days she is also a famous example of a disease predisposition test case. She made two preventive surgery for her breast, ovaries and fallopian tubes because she had inherited the faulty BRCA1 gene, which placed her at high risk of developing breast cancer and also gave her an elevated lifetime risk of developing ovarian cancer
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Ziehl–Neelsen staining. this technique is good, close to 95 per cent, but the sensitivity is low (40–60 per cent) as bacteria are emitted in an intermittent fashion that makes repetition of the sampling indispensable. The principal problem comes from the delay for a positive test, which varies from 3 to 50 days. However, molecular biological techniques have been developed with the goal of differentiating between different clinically interesting species of mycobacteria. Currently, certain commercially available kits based on the use of DNA probes marked that specifically complement the different types of bacterial ribosomal RNAs. The results are available in around 1 hour
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They result in faster diagnostic results, more targeted therapies and shorter hospitalization, which in their turn reduce health care costs..
Infectious diseases molecularTesting.
Areas of molecular diagnostics
Molecular oncology testing.
Inherited diseases molecularTesting
Tissue type testing HLA typing or histocompatibility testing
Identity testing DNAFingerprinting
Pharmacogenetics testing
For the first time in the history of medicine, diagnosis and therapy are meeting on common ground
Diagnosis Treatment
Molecular Diagnostic
Pharmacogenetics testing
Treat:
Responders and Patients
Not Predisposed to Toxicity
All patients with same diagnosis
Remove:
(1) non-responders
(2) toxic responders
Drug selection in Cancer
A. Increased growth factor production
B. Increased growth factor receptors
C. Transducer Mutations
D. Mutant transcription factors
Identity testing DNA
Fingerprinting
Inherited diseases molecular
Testing
Molecular oncology testing.
