The cellular and molecular basis of inheritance

1. The cellular and molecular basis of inheritance Dr.Mohammed T Tayeb

2. Emery's Elements of Medical Genetics Mueller RF and Young ID 11th edition 2001

3. This lecture : • Introduction: • Definition of Genetics • Cell • Chromosome • DNA • Gene • DNAComposition • Structure of DNA • The process of DNA replication • The types of DNA sequences • The genetic code • The processes of transcription and translation • The various types of mutations • Mutagenic agents and DNA repair.

4. What is genetics? • Genetics is the study of heredity, or what makes organisms differ from one another… • the transmission of characteristics from one generation to the next…

5. Genetics • Study of inheritance • How traits are passed from one generation to the next

6. Cell • The fundamental unit of life • Trillions in each human • Differentiated cells • Cells that have specialized • Only use a small part of genome • Stem cells • Can differentiate in many possible kinds of cells

7. Nucleus contains the genetic material

8. Chromosomes • Made of DNA and protein • 23 pair • Autosomes • Pair 1-22 • Sex chromosmes • X and Y • Karyotype • Picture of chromsomes

9. DNA • Made of building blocks • Adenine (A) • Thymine (T) • Cytosine (C) • Guanine (G) • Can copy itself • Is passed from one generation to another • Stores genetic information

10. Gene • Unit of inheritance • Made of DNA • Contain instructions for making a specific protein

12. The hereditary material is present in the nucleus of the cell. • Protein synthesis takes place in the cytoplasm. What is the chain of events which leads from the gene to the final products?

13. Chromosomes, DNA, and Genes Gene Nucleus Cell Chromosomes Protein

14. DNA: The hereditary materialA-Composition • Nucleic acid is composed of a long chain of individual molecules called nucleotides. • Each nucleotide is composed of nitrogenous base, a sugar molecule and a phosphate molecule.

15. 5’ end phosphate C 5’ P base Sugar S G One nucleotide A 3’ U

16. The nitrogenous bases fall into two types, purines and pyrimidines. • The Purines include adenine (A) and guanine (G). • The pyrimidines include cytosine (C), thymine (T), and uracil (U).

17. Structure of Bases Purines Pyrimidines cytosine thymine uracil adenine guanine

19. There are two different types of nucleic acid: 1- Ribonucleic acid (RNA) which contains five carbon sugar ribose. 2- Deoxyribonucleic acid (DNA) in which the hydroxyl group at the 2‘ position of the ribose sugar is replaced by a hydrogen, i.e. an oxygen molecule is lost.

20. SUGAR-PHOSPHATE BACKBONE Phosho-diester link between 3-OH of ribose and 5 phosphate of next nucleotide

21. DNA and RNA both contain A, G & C but T occurs only in DNA while U is only found in RNA. • RNA is present in the cytoplasm and in particularly high concentrations in the nucleolus of the nucleus. • DNA is found mainly in the chromosomes (nucleus and mitochondria).

22. Comparison of DNA & RNA

23. B- Structure of DNA • The DNA molecule is composed of two chains of nucleotides arranged in a double helix. • The backbone of each chain is formed by phosphodiester bonds between the 3' and 5' carbons of adjacent sugars. • The two chains being held together by hydrogen bonds between the nitrogenous bases which point in towards the centre of the helix.

26. The DNA chain end terminated by the 5' carbon atom of the sugar molecule is referred to as the 5' end (5 prime), and the end terminated by the 3' carbon atom is called the 3' end (3 prime). • In the DNA duplex the 5' end of one strand is opposite the 3' end of the other.

28. The arrangement of the bases in the DNA is not random: • G in one chain always pairs with C in the other chain. • A always pairs with T i.e. this base pairing forming complementary strands.

29. Base Pairing DNA Base Pairs DNA-RNA base pairs A A One strand of DNA RNA

30. Base Pairing DNA Base Pairs DNA-RNA base pairs One strand of DNA RNA

31. Structure of DNA 3’ end 5’ end T ------- A S 3’ 5’ P G ---------C A --------- T 3’ 5’ T ---------- A

32. Structure of RNA 5’ end phosphate C 5’ P base Ribose S G One nucleotide A 3’ U

33. DNA Bases

34. Base Pairing Hydrogen bonds adenine = thymine (in DNA) adenine = uracil (in RNA) cytosine =guanine

35. C- DNA replication

36. How genetic information is transmitted from one generation to the next? The process of DNA replication provides an answer to this question.

37. During nuclear division the two strands of the DNA helix separate through the action of enzyme DNA helicase. • Each DNA strand directing the synthesis of a complementary DNA.

38. The process of DNA replication is termed semi-conservative, as only one strand of each resultant daughter molecule is newly synthesised.

39. DNA replication, through the action of the enzyme DNA polymerase, takes place at multiple points known as origins of replication forming Y-shaped structure known as replication forks. • The synthesis of both complementary DNA strands occurs in the 5` to 3` direction. • The two strands joined together by the enzyme DNA ligase.

41. Types of DNA sequences Nuclear genes It is estimated that there are up to 80,000 genes in the genome. The distribution of theses genes varies greatly between different chromosomes. • Unique single copy genes: most human genes are unique single copy genes coding for polypeptides which are involved in or carry out a variety of cellular functions. These include enzymes, hormones, receptor and structural and regulatory proteins.

42. Multigene families: Many genes have similar functions making up what are known as multigene families. Multigene families can be split into two types: 1- classical gene families which show a high degree of sequence homology. 2- gene superfamilies which have limited sequence homology but are functionally related.

43. ORGANISATION OF GENES • Exons: are the functional portions of gene sequences that code for proteins. • Introns: are the noncoding sequences which separate the coding sequence (exons).

44. 3. The open reading frame: a sequence with variable length that dose not contain stop codons and therefore can be translated. The sequence beginning with ATG which exist at the 5' end of genes. 4. TATA boxes: These regions are about 20-30 bases to the 5' end (left) of the open reading frame (ATG). TATA boxes are thought to help direct important enzymes to the correct initiation site for transcription.

45. 5. Termination codon: the end of translation is signified by a termination triplet at the 3' end of genes. The triplet could be TAA, TAG, or TGA.

46. Gene structure Regulatory elements, promoter Coding region Start codon Stop codon CAAT TATA AUG Introns discarded TATA AAAAAAA Mature transcript AUG

47. Extragenic DNA • The reminder, 70-75%, of the human genome is made up of repetitive DNA sequences which are predominantly transcriptionally inactive.

48. Mitochondrial Chromosome • It is a circular, double-stranded DNA molecule. • All genes in mitochondrial DNA have been defined (37 genes). • They are responsible for genes necessary for mitochondrial protein synthesis, and for proteins essential to oxidative phosphorylation.

49. Transcription • Transcription is the process whereby genetic information is transmitted from DNA to RNA. • The information stored in the genetic code is transmitted from the DNA of a gene to messenger RNA or mRNA. • Every base in the mRNA molecule is complementary to a corresponding base in the DNA of the gene but with uracil replacing thymine in mRNA.

50. 1. DNA Template sense strand antisense strand 5’ 3’ 3’-OH 5’PPP RNA DNA Direction of elongation of RNA