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Genomes and genomics

Genomes and genomics. Credits: Teaching resources from School of Forest Resources and Environmental Science Michigan Tech University. Origin of terms Genomes and Genomics. The term genome was used by German botanist Hans Winker in 1920 Collection of genes in haploid set of chromosomes

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Genomes and genomics

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  1. Genomes and genomics Credits: Teaching resources from School of Forest Resources and Environmental Science Michigan Tech University SBL201 Lec 6-7

  2. Origin of terms Genomes and Genomics The term genome was used by German botanist Hans Winker in 1920 Collection of genes in haploid set of chromosomes Now it encompasses all DNA in a cell In 1986 mouse geneticist Thomas Roderick used Genomics for “mapping, sequencing and characterizing genomes” New terms: Functional genomics, transcriptomics, proteomics, metabolomics, phenomics (Omics) SBL201 Lec 6-7

  3. What is the genome? Entire genetic complement of an organism SBL201 Lec 6-7

  4. How many types of genomes are there in this world? Prokaryotic genomes Eukaryotic Genomes Nuclear Genomes Mitochondrial genomes Choloroplast genomes SBL201 Lec 6-7

  5. Why should we study genomes? • Each and everyone is a unique creation! • Life’s little book of instructions • DNA blue print of life! • Human body has 1013 cells and each cell has 6 billion base pairs (A, C, G, T) • A hidden language/code determines which proteins should be made and when • This language is common to all organisms SBL201 Lec 6-7

  6. Genome sequence can tell us… • Everything about the organism's life • Its developmental program • Disease resistance or susceptibility • How do we struggle, survive and die? • Where are we going and where we came from? • How similar are we to apes, trees, and yeast? SBL201 Lec 6-7

  7. How will the study of Genomics impact this century? • Biotechnology: more products • GMOs: More food-More problems? • Our society will not be the same! • Individualized medicine • Gene therapy • Disease free life? SBL201 Lec 6-7

  8. Now look at your neighbor What do you see? Someone is different than you! Could be that your friend differs in his/her sex, looks, nature, smartness, or simply the way he/she dresses and talks How much similarity you think you share with your friend at the gene level? 99.9% so we could fix genes if we want SBL201 Lec 6-7

  9. Now look at your own hands and legs Do they look similar? No! But they contain the same DNA in each of their cells DNA makes RNA makes proteins Different genes are expressed differently in different cells, tissues and organs of an organism Having a gene does not mean it will be expressed. SBL201 Lec 6-7

  10. Someone has a cancer gene! It is a normal gene that got mutated or changed and does not perform same job But having a gene does not mean you will get cancer Because environment has a big role in turning a gene on or off Different genes and their products also interact: microecosystem Genes do not work alone (G+E) SBL201 Lec 6-7

  11. Genomics is the study of all genes present in an organism SBL201 Lec 6-7

  12. Science of Genomics? A marriage of molecular biology, robotics, and computing Tools and techniques of recombinant DNA technology e.g., DNA sequencing, making libraries and PCRs High-throughput technology e.g., robotics for sequencing Computers are essential for processing and analyzing the large quantities of data generated SBL201 Lec 6-7

  13. Origin of Genomics Human Genome Project Goal: sequence 3 billion base pairs High-quality sequence (<1 error per 10 K bases) ACGT Immensity of task required new technologies Automated sequencing Decision to sequence other genomes: yeast and bacteria Beginnings of comparative genomics SBL201 Lec 6-7

  14. Technical foundations of genomics Molecular biology: recombinant-DNA technology DNA sequencing Library construction PCR amplification Hybridization techniques . . Log MW . . Distance SBL201 Lec 6-7

  15. Genomics relies onhigh-throughput technologies Automated sequencers Fluorescent dyes Robotics Microarray spotters Colony pickers High-throughput genetics SBL201 Lec 6-7

  16. Technology Revolution Sequencing by‘synthesis nanotechnology’approach From a Few Billion $ to $5000 Sequencing genomes in Months and Years Sequencing genomes in Minutes (14 min precisely)!! SBL201 Lec 6-7

  17. Industrial-scale Genomics Lab SBL201 Lec 6-7

  18. Bioinformatics: computational analysis of genomics data Uses computational approaches to solve genomics problems Sequence analysis Gene prediction Modeling of biological processes/network SBL201 Lec 6-7

  19. Genome sequencing Analogy: Complete works of an author in partially understood language Two approaches Page by page All at once SBL201 Lec 6-7

  20. Page-by-page sequencing strategy Sequence = determining the letters of each word on each piece of paper Assembly = fitting the words back together in the correct order SBL201 Lec 6-7

  21. All-at-once sequencing strategy Find small pieces of paper Decipher the words on each fragment Look for overlaps to assemble SBL201 Lec 6-7

  22. Genome size and gene number SBL201 Lec 6-7 Amoeba dubia: 670 billion base pairs

  23. Lessons from sequencing Variability of genome structure: Non-coding (junk?) Duplication events Transposons Microsatellites Repetitive DNAs 1 2 3 4 5 SBL201 Lec 6-7

  24. Functional Genomics Once we know the sequence of genes, we want to know the function The genome is the same in all cells of an individual, except for random mutations However, in each cell, only a subset of the genes is expressed The portion of the genome that is used in each cell correlates with the cell’s differentiated state SBL201 Lec 6-7

  25. Gene-by-gene approach to understand biological processes Analogous to understanding circuitry by following wires Choose one wire Follow circuit to transistor Follow from transistor to capacitor Follow from capacitor to power source Do again SBL201 Lec 6-7

  26. Genomics provides a parts list Provides list of all parts Parts list in itself doesn’t say how the machine works Can use to get global picture e.g., RNA expression SBL201 Lec 6-7

  27. Expression microarrays Global expression analysis RNA levels of 30x103 genes in the genome analyzed in parallel Compare with Northern blot Microarrays contain more information by many orders of magnitude SBL201 Lec 6-7

  28. Biological networks: Systems Biology Neuronal network Transcriptional network Food chain SBL201 Lec 6-7

  29. Regulatory network of sea urchin development SBL201 Lec 6-7

  30. Future of sequencing We have the genome! What’s next?(post genome era) Sequencing costs Dropping each year Could go down to $1,000/genome Opens possibility of sequencing genomes of individuals: 23andMe Greatly facilitates comparative genomics SBL201 Lec 6-7

  31. Comparative Genomics What is conserved between species? Genes for basic processes Understand the uniqueness between different species Their adaptive traits What makes closely related species different? Analyzing & comparing genetic material from different species to study evolution, gene function, and inherited disease SBL201 Lec 6-7

  32. What is compared? • Gene location • Gene structure • Exon number • Exon lengths • Intron lengths • Sequence similarity • Gene characteristics • Splice sites • Codon usage • Conserved synteny SBL201 Lec 6-7

  33. Figure 1   Regions of the human and mouse homologous genes: Coding exons (white), noncoding exons (gray}, introns (dark gray), and intergenic regions (black). Corresponding strong (white) and weak (gray) alignment regions of GLASS are shown connected with arrows. Dark lines connecting the alignment regions denote very weak or no alignment. The predicted coding regions of ROSETTA in human, and the corresponding regins in mouse, are shown (white) between the genes and the alignment regions. SBL201 Lec 6-7

  34. Improved disease diagnostics from genomics Microarray analysis of gene expression from four different types of tumors Grouping of gene expression patterns shows very clear differences among the tumors Used to tailor therapy to individuals SBL201 Lec 6-7

  35. Pharmacogenomics: drug therapies tailored to individuals Design therapies based on the individual’s genome Subtle, but important, differences in genomes Cause differences in how one responds to drugs Identify those who will suffer harmful side effects from particular drugs SBL201 Lec 6-7

  36. Prescreening based on genomes All patients with same diagnosis 1 Remove Toxic and Nonresponders 2 Treat Responders and Patients Not Predisposed to Toxic SBL201 Lec 6-7

  37. Genomics applied to agriculture Sequencing of crop-plant genomes Gene discovery for useful traits Genomewide regulatory networks to improve traits SBL201 Lec 6-7

  38. Farm-animal genomics Genome sequencing of pigs, cows, sheep, and poultry EST sequencing Agricultural pathogens Potential bioterrorism agents SBL201 Lec 6-7

  39. Ethical issues raised by genomics(ELSI) (Ethical legal, societal implications) Individual’s genome holds key to disease susceptibility Potential for misuse recognized by founders of Human Genome Project SBL201 Lec 6-7

  40. Genetic testing in the workplace Major railroad company decided to perform DNA tests on employees Wanted to identify susceptibility to carpal tunnel syndrome Equal Employment Opportunity Commission filed suit to block action SBL201 Lec 6-7

  41. Genetic modification of humans Once we know the genes responsible for particular diseases, should we “cure” the diseases? Should we also modify genes responsible for traits such as height or beauty? Should we allow the cloning of human beings? SBL201 Lec 6-7

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