Organization of the human genome

1. Organization of the human genome • Genome structure • Nuclear vs. mitochondrial genomes • Gene families • Transposable elements • Other repeated sequences

3. Organization of the human genome • Mitochondrial genome • Small (16.5 kb) circular DNA • rRNA, tRNA and protein encoding genes (37) • 1 gene/0.45 kb • Very few repeats • No introns • 93% coding • No recombination • Maternal inheritance

5. Organization of the human genome Limited autonomy of mt genomes mt encodednuclear NADH dehydrog 7 subunits >41 subunits Succinate CoQ red 0 subunits 4 subunits Cytochrome b-c1 comp 1 subunit 10 subunits Cytochrome C oxidase 3 subunits 10 subunits ATP synthase complex 2 subunits 14 subunits tRNA components 22 tRNAs none rRNA components 2 components none Ribosomal proteins none ~80 Other mt proteins none mtDNA pol, RNA pol etc.

7. Organization of the human genome • Nuclear genome • 3300 Mb • 23 (XX) or 24 (XY) linear chromosomes • 65-80,000 genes • 1 gene/40kb • Introns • 3% coding • Repetitive DNA sequences (45%) • Recombination • Mendelian inheritance (X + auto, paternal Y)

8. Organization of the human genome • Contrasting gene densities • HLA high density • Dystrophin low density

11. Organization of the human genome • Gene families • Functionally similar genes are occasionally clustered, but usually dispersed throughout the genome

13. Organization of the human genome • Genes vary in size and exon content

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17. Organization of the human genome • Genes within genes • Intron 26 of the NF1 gene contains three internal genes.

19. Organization of the human genome • Gene families defined by conserved amino acid motifs • DEAD box. • WD repeat families

21. Organization of the human genome • Ig superfamily • Cell surface receptors • Similar domain structure

23. Organization of the human genome • Clustered gene families Growth hormone 5 copies (67kb) aglobin 7 copies (50kb) Hox genes (multi) 38 four clusters Olfactory receptors 1000 in 25 large clusters

24. Organization of the human genome • Interspersed gene families Pax 9 copies Actin >20 copies Alu elements (repeats) 1.1 million LINE elements (L1) 200-500,000

26. Organization of the human genome • HLA heavy chain gene cluster • Gene fragments • Pseudogenes • Truncated genes

28. Organization of the human genome • Processed pseudogenes • Originate by reverse transcription • TPRT

30. Organization of the human genome • Chromosomal location of repeats • telomere • Centromere • LINE elements (Alu Elements) • Minisatellites

32. Organization of the human genome • Formation of higher order repeat units

34. Organization of the human genome • Human transposable elements

36. Organization of the human genome • Transposable elements with RNA intermediates • Endogenous retroviruses • Retrotransposons • Retropseudogenes

38. Organization of the human genome • Human transposable elements • Alu elements • LINE elements

40. Organization of the human genome • Mobile elements and gene structure • RB1 region • Alu • LINE • Simple sequence repeats