GENETICS an Introduction

1. GENETICS an Introduction

2. Aim of These Sessions By the end of these sessions, the students should be able to demonstrate the ability to discuss the normal and genetic mechanisms that underlie several normal and disease processes. • The Aim of these session is to provide the student with a sound understanding of normal and disease processes at the genetic level. • These sessions will be comprised of two different modalities of expressions such as SEMINARS & LECTURES. • Each session will cover the general features of the normal and disease condition(s), and will focus on current understanding of the biochemical effects of normal conditions as well as biochemical defects (metabolic, structural or genetic) which underlie the disease state.

3. Lectures • Chemistry, classification and characteristics of Purine and Pyrimidine Bases • Chemistry, classification and characteristics of Nucleosides and Nucleotides. • Classification, Function and occurrence of nucleotides in human tissue and role of Nucleotides in the Human Body. • Role of Cyclic AMP and Cyclic GMP in the body. • Protein Synthesis • Chromosome structure, classification and abnormalities • Genetic Variation and mutations • Genetic patterns of inheritance • Inborn errors of metabolism • Cancer genetics, • Gene therapy, • Genetic counseling, and ethical issues and decision making in medical genetics. • Genetic screening

4. Genetic Information • Gene – basic unit of genetic information. Genes determine the inherited characters. • Genome – the collection of genetic information. • Chromosomes – storage units of genes. • Human has 23 pairs of chromosomes • These 46 chromosomes contain 6 billions individual characters of the genetic code. • Human body is made up of 75 trillion cells • Every cells has a nucleus • In the nucleus they contain Genes • 99.9 % of genes are present in nucleus • Few genes are present in Mitochondria • Genes are small part of DNA • DNA - is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life • DNA is made up of Nucleotides • Nucleotides is comprised of Sugar, Nitrogenous base and phosphate

5. Human Genome Human diploid cells contain 46 chromosomes arranged in 23 pairs • 2 sex chromosomes (X,Y): XY – in males. XX – in females. • 22 pairs of chromosomes named autosomes. • Chimpanzee contain 24 pairs of chromosomes • Cow contain 30 pairs of chromosomes • Chicken contain 39 pairs of chromosomes • Bnana contain 11 pairs of chromosomes

6. Who determines the male or female Gender • Is the mother • Is the father • Or is it by chance from any of the two 50% Girls 50% Boys

7. Genotypes Phenotypes • At each locus (location of a gene/marker on the chromosome) there are 2 genes. These constitute the individual’s genotype at the locus. • The expression of a genotype is termed a phenotype. For example, hair color, weight, or the presence or absence of a disease.

8. Genetics Review DNA T A C G C T T C C G G A T T C A A Transcription RNA A U G C G A A G G C C U A A G U U Translation Protein Amino Acids ABCDE

9. Protein Synthesis Translation of the Genetic Code

10. Proteins/ Gene Expression • Proteins make up all living materials

11. Proteins are composed of amino acids – there are 20 different amino acids • Different proteins are made by combining these 20 amino acids in different combinations

12. Proteins are manufactured in the ribosomes under the strict control and order of DNA. • The DNA language is made up of letters which are ATGCATATGGAATCAG • These letters forms Words • ATC GCA GGA AUU AUG • These words make sentences

13. Protein Synthesis

14. DNA and Protein Synthesis • DNA contains the genetic information to make amino acids • Amino acids combine to make proteins • These proteins determine the physical traits of an organism and control cellular functions. • Proteins do everything, and DNA gets all the credit!

15. Transcription & Translation • Transcription is the Reading of the DNA and Changing the code to mRNA. • Translation is changing the mRNA into a trait by Using tRNA to interpret the mRNA.

16. Introns & Exons • DNA has regions of coding and non-coding. The regions of DNA that code for proteins or traits are called EXONS, while the regions that do not code for proteins are called INTRONS.

17. Making a Protein—Transcription • First Step: Copying of genetic information from DNA to RNA called Transcription • Part of DNA temporarily unzips and is used as a template to assemble complementary nucleotides into messenger RNA (mRNA).

18. Site of Transcription&Translation • Transcription occurs inside the nucleus in a two step sequence of events. • Pre-mRNA includes both introns and exons for the gene. • mRNA is only the coding portion (exons). • Translation occurs in the cytoplasm at the ribosomes. • Reminder: The are three (3) types of RNA • Messenager (mRNA) • Transfer (tRNA) • Ribsomal (rRNA)

19. A U G G G C U U A A A G C A G U G C A C G U U Messenger RNA • This is a molecule of messenger RNA. • It was made in the nucleus bytranscription from a DNA molecule. codon mRNA molecule

20. ribosome A U G G G C U U A A A G C A G U G C A C G U U Ribosome A ribosome on the rough endoplasmic reticulum attaches to the mRNA molecule.

21. Amino acid tRNA molecule anticodon U A C A U G G G C U U A A A G C A G U G C A C G U U Transfer RNA A transfer RNA molecule arrives. It brings an amino acid to the first three bases (codon) on the mRNA. The three unpaired bases (anticodon) on the tRNA link up with the codon.

22. U A C C C G A U G G G C U U A A A G C A G U G C A C G U U Transfer RNA Another tRNA molecule comes into place, bringing a second amino acid. Its anticodon links up with the second codon on the mRNA.

23. Peptide bond C C G U A C A U G G G C U U A A A G C A G U G C A C G U U Transfer RNA A peptide bond forms between the two amino acids.

24. C C G U A C A U G G G C U U A A A G C A G U G C A C G U U Transfer RNA The first tRNA molecule releases its amino acid and moves off into the cytoplasm.

25. C C G A U G G G C U U A A A G C A G U G C A C G U U Transfer RNA The ribosome moves along the mRNA to the next codon.

26. C C G A A U A U G G G C U U A A A G C A G U G C A C G U U Another tRNA molecule brings the next amino acid into place.

27. C C G C C G A U G G G C U U A A A G C A G U G C A C G U U Polypeptide chain A peptide bond joins the second and third amino acids to form a polypeptide chain.

28. G U C A C G A U G G G C U U A A A G C A G U G C A C G U U Termination (stop) codon The process continues. The polypeptide chain gets longer. This continues until a termination (stop) codon is reached. The polypeptide is then complete.

29. DNA and Protein Synthesis - Summary

30. Use one of the codon charts on the next page to find the amino acid sequence coded for by the following mRNA strands. CAC/CCA/UGG/UGA ___________/___________/___________/____________ AUG/AAC/GAC/UAA ___________/___________/___________/____________

31. 2nd Base 1st Base 3rd Base CAC/CCA/UGG/UGA ___________/___________/___________/____________ Histidine Proline Tryptophan Stop

32. AUG/AAC/GAC/UAA ___________/___________/___________/____________ Methionine Asparagine Aspartic Acid Stop

33. DNA and Mutations • Mutations are any changes that take place in DNA: • Can be spontaneous or caused by mutagens • ex: Chemicals, high temperatures, UV light, • radiation • Can change the genetic code, and be replicated • when forming new body cells. • In sex cells, can be passed on to offspring.

34. DNA and Mutations – Lets looks at different mutations THE DOG BIT THE CAT

35. DNA and Mutations - Substitution • THE DOG BIT THE CAT • Substitution - Replace just one letter: • THE DOG BIT THE CAR

36. DNA and Mutations - Deletion THE DOG BIT THE CAT Deletion: Delete just one letter (T): THE DOG BIT HEC AT

37. DNA and Mutations-Insertions • THE DOG BIT THE CAT • Insertion - Add just one letter (E): • THE DOE GBI TTH ECA T

38. Knowing exact cause of disease at molecular level –better understanding of etiopathogenesis of disease process. Correction at level of missing biochemical end product e.g. thyroxine administration Correction at level of excess substrate e.g. low Phe diet in PKU Replacement of a defective enzyme e.g. Gaucher disease. Advantages of Knowing Genetics

39. Replacement of defective protein e.g. Factor VIII in hemophilia Increasing the action of less active mutant enzyme by giving more cofactor or co enzyme e.g. Vit. B12 for methylmalonic aciduria Gene therapy – an ongoing area of research which would is expected to offer the final solution to genetic diseases. Advantages of Knowing Genetics

40. Gene Therapy • Gene therapy is a technique used for correcting defective genes responsible for disease development • Gene therapy is permissible in humans at present for somatic cells only. • Major problem is complexity and efficacy

41. Gene Therapy • Types of gene therapy : • Replacement : Mutant gene removed and replaced with a normal gene • Correction : Mutated area of affected gene would be corrected and remainder left unchanged • Augmentation : introduction of foreign genetic material into a cell to compensate for defective product of mutant gene “ only gene therapy currently available today's”.