Lecture7,8
- 1. Pharmacogenetics Refers to the genetic differences in individuals Different metabolic pathways Affecting response to drugs 106,000 deaths in US Vitamin E helps cure cardiovascular disease in some. Pharmacogenetics VS Pharmacogenomics -Germline mutations -Somatic mutations in tumor cell lines Pharmacogenomics: Dihydropyrimidine dehydrogenase (DPD); UDP- glucuronosyltransferase 1-1 UGT1A; thiopurine S- methyltransferase (TPMT); Cytidine deaminase CDA Ref: http://en.wikipedia.org/wiki/Pharmacogenetics
- 2. Somatic Cell Genetics Somatic Cell mutations Cancer Ageing Mosaicism PKU: Phenylketonuria hyperphenylalaninemia Most Mutations are recessive
- 3. type of mutation mechanism frequency per cell division 1. mistakes in DNA replication ~10-10/basepair point mutation 2. DNA damage by chemical ~10-5/gene mutagens (or by radiation) ~0.5/cell and misrepair 1. unequal crossing over 2. misalignment during DNA replication submicroscopic deletion or 3. insertion of mobile included in the above insertion element 4. DNA damage by chemical mutagens (or by radiation) and misrepair 1. unequal crossing over microscopically visible 2. DNA damage by chemical deletion, translocation or 6 x 10-4 mutagens (or by radiation) inversion and misrepair loss of a whole chromosome missegregation at mitosis 1 in 100
- 4. Genetics Of Globin Triplet Disorder Ref: http://en.wikipedia.org/wiki/Hemoglobin
- 5. Genetics of Haemoglobin triplet disorder Sickle Cell Anemia: Mutation in HBB CTC -> CAC; Glutamic acid -> Valine Ref: http://en.wikipedia.org/wiki/Sickle-
- 6. Prevalence of Sickle Cell Anemia Heterozygotes have distinct advantages over homozygotes. Selective advantages in case of malaria infection.
- 8. MicroArray Ref: http://www.reproduction-online.org/content/130/1/1/F1.expansion.html
- 9. MicroArray http://en.wikipedia.org/wiki/DNA_microarray
- 10. MicroArray Bioinformatics 1. Experimental Design 2. Standardization 1. Background correction 2. Normalization 3. Differential expression Analysis 3. Statistical Analysis 4. Data Warehousing Probes and Genes
- 11. Application of MicroArray Expression Profiling Comparative Genome Hybridization Detecting protein bound region (Chip-Seq) Alternate Splicing Fusion Genes Tiling Array
- 12. Physical Map of Chromosome
- 13. Genetic Mapping
- 14. SSR Loci Micro-satellite markers Simple sequence Repeats (2-6 nt) Variable Number of Tandem Repeats (VNTR) (CA)n repeat varies between alleles. Repetitive regions vary in different alleles because of slipped strand mispairing