Globin gene defect in humans

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.

7. Micro Array
Ref: http://en.wikipedia.org/wiki/DNA_microarray

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