1. Diagnostic Testing Noelle Lewis Molecular Biology

2. Principles of Genetic testing A genetic diagnostic test identifies a specific indicator that shows whether a person will have or develop a disorder A genetic diagnostic test identifies a specific indicator that shows whether a person will have or develop a disorder Positive test results indicate a person has the indicator Positive test results indicate a person has the indicator Negative test results indicate the indicator is absent Negative test results indicate the indicator is absent

3. Principles of Genetic testing False positives and negatives are common False positives and negatives are common A false positive could result in a person having unnecessary anxiety and often unnecessary treatment A false positive could result in a person having unnecessary anxiety and often unnecessary treatment A false negative could result in the person thinking they do not have the disease when they actually do A false negative could result in the person thinking they do not have the disease when they actually do Clinical tests are adjusted to minimize the occurrence of false results Clinical tests are adjusted to minimize the occurrence of false results

4. Principles of Genetic testing Sensitivity and specificity are used to judge the clinical validity of a test Sensitivity and specificity are used to judge the clinical validity of a test Sensitivity is the fraction of correctly identified people who truly have the indicator- TP Sensitivity is the fraction of correctly identified people who truly have the indicator- TP TP+FN TP+FN Specificity is the fraction of people who do not have the indicator- TN TN+FP A condition is likely present when a test is positive and specificity is high.

5. Testing for genetic disorders A test used to identify an inherited disorder A test used to identify an inherited disorder The indicator may be a chromosome, protein, metabolite, or nucleic acid sequence The indicator may be a chromosome, protein, metabolite, or nucleic acid sequence Chromosome abnormalities are detected by karyotype staining or fluorescent in situ hybridization (FISH). Chromosome abnormalities are detected by karyotype staining or fluorescent in situ hybridization (FISH). Biochemical and immunological assays of blood and urine test amino acids, organic acids, and metabolites or proteins Biochemical and immunological assays of blood and urine test amino acids, organic acids, and metabolites or proteins -The Guthrie test-Phenylketonuria in infants

6. Genetic testing Accumulation or deficiency of a metabolit can be detected by tandem mass spectromery Accumulation or deficiency of a metabolit can be detected by tandem mass spectromery The m/z pofile is compared to known standards to identify and quantify the indicator The m/z pofile is compared to known standards to identify and quantify the indicator Tandem MS is efficient and can detect and measure the amounts of many different indicators Tandem MS is efficient and can detect and measure the amounts of many different indicators

7. Genetic testing Other methods include assays that use the known human genetic sequence to identify mutations, single-strand conformation polymorphism, denaturing gradient gel electrophoresis, and denaturing high- performance liquid chromatography Other methods include assays that use the known human genetic sequence to identify mutations, single-strand conformation polymorphism, denaturing gradient gel electrophoresis, and denaturing high- performance liquid chromatography