1. Human Genome Structure & Organization
Professor Samar Kamal Kassim, H3ABioNet/H3Africa
Co-Chair, Genomics Education and Coordinated Training Working Group (ECTWG), H3Africa Consortium
Medical Biochemistry & Molecular Biology Department
Faculty of Medicine, Ain Shams University

2. Ain Shams University

3. Learning Objectives Understand the DNA structure
Understand genes and their relation to organism characters
Explain the relation of genes to chromosomes
Understand how chromosomes are formed
Define what is meant by genome
Have a basic background about epigenetics

4. The fingerprint that’s inside your body!!
DNA
The fingerprint that’s inside your body!!

5. DNA ….Where?
Chromosomes in nucleus of eukaryotes
In mitochondria,

6. DNA
All of the genetic information in any living creature is stored in deoxyribonucleic acid (DNA)
DNA is a polymer of four simple nucleic acid units, called nucleotides.

7. DNA Four nucleotide bases: Purines: adenine (A) and guanine (G)
Pyrimidines: cytosine (C) and thymine (T)
Each nucleotide consists of
One base (a purine or a pyrimidine)
sugar (ribose in RNA and deoxyribose DNA)
one or more phosphate groups.

8. Pairing T A C G DNA G A C T U A RNA C G X 1.08 nm 1.08 nm N N O O H H

9. H-bonding of adjacent antiparallel DNA strands form double helix structure

10. Single strand of DNA

11. The Notation for Nucleic AcidsG A T C G 5’ 3’ P OH
5’ pApTpCpGpApTpCpG-OH 3’
5’ pATCGATCG-OH 3’
ATCGATCG

12. DNA
DNA and its building blocks. DNA is made of four types of nucleotides, which are linked covalently into a polynucleotide chain (a DNA strand) with a sugar-phosphate backbone from which the bases (A, C, G, and T) extend. A DNA molecule is composed of two DNA strands held together by hydrogen bonds between the paired bases. The arrowheads at the ends of the DNA strands indicate the polarities of the two strands, which run antiparallel to each other in the DNA molecule. In the diagram at the bottom left of the figure, the DNA molecule is shown straightened out; in reality, it is twisted into a double helix, as shown on the right.

13. Genes and Chromosomes
Genetic information can be stored in several DNA molecules (chromosomes) that are present in pairs.
Each chromosome pair contain two similar DNA molecules, one from each parent

14. Chromosomal structure and human genome
A typical human cell contains 23 pair of chromosomes.
Each chromosome is composed of 2 chromatids joined at centromere.
Each chromatid contains a DNA molecule.

15. Eukaryotic chromosome

16. Homologous chromosomes
Cell
Nucleus
23 paternal
directories
Replication
3,000 MB
Total 35,000 files
23 maternal
equivalents
In 46 chromosomes
Nucleus
23 x 2
¤Hأ‏ 23 ±ّ¬V¦âإ餤،F³o ±ّ¬V¦âإé،C (X «¬)،C
23 ­س¤l¥ط؟‎¤¤،C³o 23 (إم©ت°ٍ¦])،C¦س³o¨â®M¤l¥ط؟‎،A¬O¤ہ§O¥ر¨â­س¤£¦Pھ؛¨س·½ (؛ë¤l¤خ§Z¤l) ©ز±o¨ىھ؛،C
­س¤l¥ط؟‎¥‎½ئ»s©ز§tھ؛ہة®× (¤W¹د¥k°¼ X §خ¬V¦âإé)،A¨C­س X 46 ­س¤l¥ط؟‎،A»P­ى¥‎ھ؛؛د¤ù¨S¤°»ٍ¤£¦P،A©ز¥Hإé²س­M¤ہµُ«ل،A¤l²س­M»P­ى¥‎ھ؛²س­M¬غ¦P،C 23 ±ّ،C
Before cell
division
Homologous chromosomes
Juang RH (2004) BCbasics

17. Chromosomal structure and human genome
The total DNA of these chromosomes is called human genome. The DNA of one human genome (23 chromosomes), placed end to end, would extend for about one meter long. Most human cells are diploid and each cell contains a total of 2 m of DNA.
It contains information equal to some 600,000 printed pages of 500 words each!!!
(a library of about 1,000 books)

18. Chromosomal structure and human genome
Can you imagine how much large DNA should be packaged into the small nucleus?

19. Chromosomal structure and human genome
The long DNA interacts with many proteins (Nucleoproteins) to form Nucleosomes

20. Packaging of DNA

21. Chromosomal structure and human genome
Nucleosomes are arranged to form Chromatin that can be effectively packaged into the nucleus

22. Chromatin fibers
A group of nucleosomes about six are further supercoiled to form a more condensed structure called chromatin fibers

23. Chromosomes
The chromatin fibers are further supercoiled to form loops and condensed to form chromosomes.

25. Genes Units of heredity
Encode proteins that form the shape and characters of the organism.
Gene is present on the chromosome in a site called Locus
As chromosomes are present in pairs, each gene is also present twice, each one is called an allele

26. Genes Each pair of Genes carries the code for a certain character.
Each single gene of the pair is called an allele,
The two alleles although carry the same character, however, may be different forms of this character.

27. Organization of Genes
The organization of genes on a human chromosome. (A) Chromosome 22, one of the smallest human chromosomes, contains 48 × 106 nucleotide pairs and makes up approximately 1.5% of the entire human genome. Most of the left arm of chromosome 22 consists of short repeated sequences of DNA that are packaged in a particularly compact form of chromatin (heterochromatin). (B) A tenfold expansion of a portion of chromosome 22, with about 40 genes indicated. Those in dark brown are known genes and those in light brown are predicted genes. (C) An expanded portion of (B) shows the entire length of several genes.

28. Some chromosomes are richer in genes than others
Number of Nucleotides In Exons

29. Chromosomes
Two closely related species of deer with very different chromosome numbers. In the evolution of the Indian muntjac, initially separate chromosomes fused, without having a major effect on the animal. These two species have roughly the same number of genes. (Adapted from M.W. Strickberger, Evolution, 3rd edition, 2000, Sudbury, MA: Jones & Bartlett Publishers

30. Eukaryotic Genome
Genome is total DNA content in all the chromosomes of a cell.
It contains more than 30,000 genes.

31. Epigenetics

32. Epigenetics
The modification of chromatin structure and activity without change in the DNA base sequence is known as Epigenetic Changes or Chromatin Remodeling.

33. Epigenetics
This modification results is either expression or inhibition of the gene.

34. Chromatin remodeling
The inter-conversion of active and inactive forms of chromatin (genes) is called chromatin remodeling.

35. Chromatin Remodeling
Examples of Chromatin Remodeling (Epigenetic Changes) is attaching a modifying group as Methyl or Acetyl group

36. Regulation of Gene expression
Methylation
Acetylation

37. Regulation of Gene expression
Gene Inhibition
Methylation
Acetylation
Gene Stimulation

38. DNA Methylation

39. DNA Methylation

40. Thanks You