EECS 730 Introduction to Bioinformatics Genome and Gene

1. EECS 730Introduction to BioinformaticsGenome and Gene Luke Huan Electrical Engineering and Computer Science http://people.eecs.ku.edu/~jhuan/

2. Overview • Genome structure • Mendelian genetics • Linkage and recombination EECS 730

3. Chromosome Painting EECS 730

4. Chromosome structure Short arm: p long arm: q EECS 730

5. A few terms • A chromosome contains two (almost) identical copies of DNA molecules. Each copy is called a chromatid and two chromatids are joined at their centromeres. • Chromosomes and regions in a chromosome are named. For example by notation 6p21.3, we mean • 6 : chromosome number • p : short arm (from petit in French), q for long arm • 21.3 : band 21, sub-band 3 (microscope) EECS 730

6. Chromosomes in Cell Division EECS 730

7. Chromosome Structure EECS 730

8. Chromosome structure EECS 730

9. Mendelian Genetics • Mendel started genetics research before we know chromosome and gene • Phenotype-- observable difference among members in a population • For example: hair color, eye color, blood type • What controls a phenotype? • This is the question that Mendel tried to answer • Is still the central question of modern genetics • He used pea, a simple organism, and quantitative method to study phenotypes. • We call a quantitative study of biology computational biology now. EECS 730

10. Mendel’s Peas EECS 730

11. Mendel’s Peas EECS 730

12. X F0 F0 Mendel’s Experiments • He bred green peas with yellow peas • In genetics, we call this practice cross(or mating) -- sexual reproduction between 2 organisms • Parental strains (denoted by P0 or F0)-- originally crossed organisms EECS 730

13. Mendel’s Results • Mendel collected results for F1 and F2 generations • F1 generation-- offspring of the F0 generation (parents) green yellow ratio F1 generation 227 0 EECS 730

14. Mendel’s Explanation: Gene Model • Model postulated that there are something called “genes” that controls the phenotype • For the time being, let’s assumes that each organism always have two copies of the same gene. One from “father” and the other from “mother”. • Some genes are dominant: the associated phenotype is visible in the F1 generation, e.g. green seed color • Some genes are recessive: the associated phenotype is invisible in the F1 generation, e.g. yellow seed color • How could we tell whether the gene model is correct or not? EECS 730

15. Mendel’s New Experiments • F2 generation-- offspring of F1 generation crossed to itself • What should we expect to see in F2? • Green seed: ¾ • Yellow seed: ¼ • His experimental results: green yellow ratio F1 generation 227 0 F2 generation 593 193 3.07 EECS 730

16. Continuing the experiments • If we pick up yellow seed from the F2 generation and breed from them, what should we expect: • All yellow (since yellow are recessive and hence we have both genes that contribute to yellow) EECS 730

17. Continuing the experiments • If we pick up green seed from the F2 generation and cross these organisms, what should we expect: • Green seeds: 8/9 • Yellow seeds: 1/9 • If we pick up green seed from the F2 generation and cross an organism with itself, what should we expect: • Some produce only green seeds: 1/3 • Some produces both green seeds and yellow seeds: 2/3 EECS 730

18. Mendelian Genetics Importantly, Mendel went another step further looking at F3 plants 593 crosses 201 green offspring only 392 green and yellow F3 2:1 ratio green: yellow 193 crosses 193 yellow offspring only 0 green pea pods overall 1/4 F2 matings green, 1/2 F2 matings mixed, 1/4 F2 matings yellow 1:2:1 ratio for all F2 crosses EECS 730

19. Genetics by Diagram X Adult F0: X More terminology: Gamete -- reproductive cell Zygote-- fertilized egg gamete Zygote F1: Mendel's Principle of Segregation: In the formation of gametes, the paired gene separate such that each gamete is equally likely to contain either one. gamete Zygote F2: EECS 730

20. Another Rule Principle of Independent Assortment: segregation of any pair of alleles is independent of other pairs in the formation of gametes adult gametes EECS 730

21. Our Explanation of Mendelian Genetics The two chromatids belong to the same chromosome separated randomly during a cell division EECS 730

22. Gene linkage • Experiments: white eyed female flies cross with wild type males (red eye, dominant) • What should we expect: • All red eyed flies in F1 • No! We have 50% red eyed and 50% white eyed • Why? • A further study show that all red eyed are female and all white eyed are male EECS 730

23. w w w + + Y w Y Female, red eye Male, while eye Gene Linkage: • Morgan’s explanation: X EECS 730

24. Recombination • F1 generation: white eyed, miniature wing female crossed to wild type male • F2 generation (ie. heterozygous female crossed to a wm male. • We know that white eye gene and the miniature gene are in the same chromosome • What should we expect: • female: 50% wm, 50% normal • male: 50% wm, 50% normal EECS 730

25. Recombination • What we have: F2 generation (ie. heterozygous female crossed to a wm male: • white eyes, normal wings 223 • red eyes, miniature wings 247 • red eyes, normal wings 395 • white eyes, miniature wings 382 • We have some combination that does not appear in parents! EECS 730

26. Recombination • chromtides exchange their DNA components. EECS 730

27. Modern Genetics • Forward genetics: given a phenotype, how do we identify the genes that contribute to the phenotype? • Cancer, Parkinson's Disease,… • Reverse genetics: given a gene, how could we know what are the phenotype that the gene might control? • Diagnostics EECS 730

28. How are Phenotypes Caused? • Through a biochemical pathways: • Genes, mRNA, and proteins A B C D E W X Y Z EECS 730

29. Chromosome structure EECS 730

30. Chromosome Structure Chromosomes are made up of a single continuous DNA molecule can’t be straight-- would be many times length of the cell Chromatin: ordered aggregate of DNA and proteins visible in the cell cycle EECS 730

31. Chromosome Structure heterochromatin: dense, compact structure during interphase generally near the centromere and telomeres (chromosome ends) composed of long tracks of fairly short base pair repeats few genes compared to euchromatin euchromatin: less dense DNA that only becomes visible after condensing typically has genes being actively transcribed EECS 730

32. Gene Expression • genes are located at specific places on the chromosome (loci) • regions corresponding to genes are transcribed • sequences flanking the coding sequence control the start and stop of transcription • not all genes are expressed at the same rates or at the same times } EECS 730

33. Regulation of Expression • gene expression is regulated by proteins binding to promoter and regulatory regions • regulatory proteins (eg., hormones) can 'turn on' or 'turn off' genes according to other factors EECS 730

34. Steroid Hormone Action • nuclear receptors are transcription factors • hormone binding exposes DNA binding domain • binding to promoter region turns genes 'on' or 'off' • tend to have a longer lasting effect EECS 730

35. Ribosomes and Translation EECS 730

36. Translation EECS 730

37. EECS 730

38. Compartments and Sorting Secretion (export) Other Signal sequences target proteins Secretory Pathway EECS 730