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  1. 1. PHARMACOGENETICS •"Genotype" is an organisms full hereditary information• "Phenotype" is an organisms actual observed properties,such as morphology, development or behavior •An organisms genotype is a major (the largest by far for morphology) influencing factor in the development of its phenotype •Monozygous (i.e. identical) twins: Identical twins share the same genotype, since their genomes are identical; but they never have the same phenotype, although their phenotypes may be very similar. •Their fingerprints are never completely identical •The terms "genotype" and "phenotype" were created by Wilhelm Johannsen in 1911.
  2. 2. PHARMACOGENETICS• Elementary genetics - Genetic Control. The genes control the lifeprocesses of each body cell. In an individual, eachcell has identical genes. Overall, genes determine therange of potentiality of an individual, and theenvironment develops it - Through the arrangement of its nucleotides,the gene provides coded information for theconstruction of proteins -A chromosome is a very long double-helixthread of DNA. Thus, each chromosome consists of alarge number of genes. The genes have very specificlocations along the length of each chromosome
  3. 3. ELEMETARY GENETICS CONT….• The 46 chromosomes of the human cell occur in pairs. Thus, we may say that there are two sets, with 23 chromosomes in each set• Of the 23 different pairs of chromosomes, 22 deal with the body in general and are called autosomal chromosomes. The last pair is called the sex chromosome• There are two kinds of sex chromosomes--X and Y. When an individuals cells each have two X chromosomes (XX), the individual is genetically a female. On the other hand, when an individuals cells each have one X and one Y chromosome (XY), that individual is genetically a male
  4. 4. GENE AND ALLELEDefinitions:a gene is the basic instruction—a sequence of nucleicacids (DNA or, in the case of certainviruses RNA), while an allele is one variant of thatgene. Referring to having a gene for a disease forexample, sickle-celldisease is caused by a mutant allele of a haemoglobingene. allele is an alternative form of a gene (one• An member of a pair) that is located at a specific position on a specific chromosome. These DNA codings determine distinct traits that can be passed on from parents to offspring.
  5. 5. ELEMENTARY GENETICS• The two types of cell division are:(1) Mitosis. New cells must be produced for replacement of worn-out cells and for growth and development of the individual. For these purposes, the existing cells undergo cell division and produce new cells. The usual process of cell division is called mitosis.(2) Meiosis: Meiosis is a type of cell division which occurs only in the gonads. It results in the formation of the gametes, or sex cells. Here the two sets of chromosomes separate, andone set of 23 goes to each of the gametes. Thus, meiosisinvolves a reduction division. The final result is that eachgamete has only one set of 23 chromosomes (haploidcondition).
  6. 6. • Genotype/Phenotype.The genotype is the actual genetic makeup of anindividual. The phenotype is the physical andfunctional makeup of an individual as determinedboth by the genotype and the environment.• Dominant/Recessive. Consider a gene in one set of chromo-somes and thecorresponding gene in the other set. If one of thegenes alone can produce a characteristic of thephenotype, the gene is said to be dominant. If bothgenes must be the same to produce a characteristic ofthe phenotype, then the genes are recessive. In asituation where one of the pair is dominant and theother is recessive, the dominant gene determines theultimate characteristic
  7. 7. • Homozygous/Heterozygous. Again, consider a gene in one set of chromosomes andthe corresponding gene in the other set. If the two genes arethe same, we say that the individual is homozygous for thattrait. If the two genes are different, we say that the individual isheterozygous for that trait.• Fraternal/Identical. In multiple births, two or more of the newborn may ormay not resemble each other closely. They may resemble eachother in sex (gender) and other physical and functional traits. (1) If two of the individuals are different, they are calledfraternal twins. (2) If they closely resemble each other, they are calledidentical twins. Identical twins are believed to originate in acommon zygote, which separates into two entities at a veryearly stage. Thus, identical twins have the same geneticmakeup. However, one is often right-oriented and the otherleft-oriented
  8. 8. • Rarely the spontaneous alterations in the base sequence of a particular gene arise from a number of sources e.g. as errors in DNA replication and the aftermath of DNA damage. These errors are called mutations
  9. 9. A. PM poor metabolizer, absent or greatly reduced ability to clear or activate drugs.B. IM intermediate metabolizer. Heterozygotes for normal and reduced activity genes.C. EM Normal Metabolizer. The norm.D. UM Ultra Metabolizer. Greatly increased activity accelerating clearance or activationPOPULATION FREQUENCY OF CYTOCHROME P450 (CYP) GENOTYPESGene PM IM EM UMCYP2D6 10% 35% 48% 7%CYP2C9 2-4% >35% ~60% N/ACYP2C19 2-20% 24-36% 14-44% 30%
  10. 10. • Gene therapy is an experimental form of treatment whereby sequences of nucleic acids (i.e., genes) are delivered to cells to change their biologic function.• For the genetic disorders, the aim is to replace a defective gene with the normal counterpart.• The delivered genetic material undergoes transcription and translation using the host cell’s machinery, leading to in situ production of the normal protein and thereby correction of the phenotypic defect.• The replacement to one of using genes as an indirect method for delivering a variety of therapeutic proteins.• These proteins may be identical to the natural human protein, whereby therapy occurs via the magnitude and location of expression, or the delivered genes may be engineered to produce novel proteins with distinct therapeutic properties
  11. 11. • From a medical perspective, it is helpful to divide the genetic contribution to disease into three categories: high- penetrance monogenic or chromosomal disorders, monogenic versions of common disorders, and complex multifactorial disorders. Each of these has an impact on medical practice in distinctive ways.• High-penetrance monogenic or chromosomal disorders are the “genetic conditions.” They include single gene disorders, such as neurofibromatosis Marfan syndrome cystic fibrosis, and chromosomal abnormalities, such as trisomy 21 (Down syndrome)• They include mendelian dominant or recessive disorders, sex- linked disorders, and more recently discovered conditions that are due to mutations within the 16.6 kb mitochondrial genome.• They also include major chromosomal aneuploidy syndromes and syndromes resulting from duplication or deletion of small regions of the genome that result in either reproducible syndromes, such as Williams syndrome (deletion of the elastin locus on chromosome 7), or nonspecific mental retardation.