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Genetics 321 From Mendel to Genomes 10 Weeks Genetics 321 From Mendel to Genomes 10 Weeks

Jeff Young, Botanist email: via contact form on web site x 3638 Office: BI Jeff Young, Botanist email: via contact form on web site x 3638 Office: BI 412 Office Hours MW: 1: 00 - 2: 00 pm, F: 10 - 11 …by appointment. Arabidopsis thaliana Genome-based study of plant physiology and environmental responses.

Class Business • Bulletin Board outside of BI 463, – Answer Keys, – etc. Class Business • Bulletin Board outside of BI 463, – Answer Keys, – etc. • Online Materials. . . http: //biol. wwu. edu/young/321 . . . via Biology Department Home Page -> Courses -> Jeff Young’s Courses -> Genetics.

Itinerary • M W F, 11: 30 - 12: 50, 5 minute break (~12: Itinerary • M W F, 11: 30 - 12: 50, 5 minute break (~12: 15). • M & F, Usually, questions and answers after break, • W, (without exception) quiz 12: 35 - 12: 50, • All midterms in class, 12: 35 - 12: 50, – Final: Friday, December 11, 10: 30 pm - 12: 30 pm

Essential Genetics: A Genomics Perspective by Hartl and Jones, 4 th ed. ISBN: 0 Essential Genetics: A Genomics Perspective by Hartl and Jones, 4 th ed. ISBN: 0 -7637 -3527 -2 Text Assignments: • Unless amended in class, all reading assignments listed on the syllabus are required, • Additional reading assignments will be made, • You will be responsible for ‘in class’ additions and changes made to the syllabus.

Grades W Three hourly exams plus final exam (450 pts), â You will have Grades W Three hourly exams plus final exam (450 pts), â You will have the full session time to complete each exam, â You will be allowed one 11” x 8. 5” crib sheet, one side, for each exam, â Exams - 150 points each, Final Exam cumulative. W Quizzes will be given every Wednesday (total 100 pts), â will cover the basics of the assigned reading (including that day's assignment), â quizzes 12. 5 points each, ~15 minutes, â quizzes may be taken in teams of two (except Q #1 and #2), â No Make-up Quizzes, absolutely no exceptions, â can drop two (2) lowest quiz scores (except Q #1 and #2). W Total course points - 550

Extra Credit • e-mail me a synopsis of a news story concerning Genetics, in Extra Credit • e-mail me a synopsis of a news story concerning Genetics, in the body of the email, 1 per email, • 1 point each for up to 15 points, – maximum, 2 per week, • journal, date, byline, who, where, what and the significance, • in English sentences, – not an automatic point, – must be well presented.

Extra Credit Sources • paper newspapers, • online newspapers, – do not just cut Extra Credit Sources • paper newspapers, • online newspapers, – do not just cut and paste, – I reserve the right to be the final judge and arbiter of valid extra credit contributions, • you will receive automatic notification(within 24 hours) that your email got to me. This is not automatic approval. • if I suspect that liberties are being taken, your extra credit account will be tallied to zero permanently, • I’ll let you know if I have a problem with your entry. • no professional journals.

Genetics 321 From Mendel to Genomes 10 Weeks Genetics 321 From Mendel to Genomes 10 Weeks

Genomicston Geneticsville Young Pass Get behind Map Nature Lake Hard Mountains Don’t work problems Genomicston Geneticsville Young Pass Get behind Map Nature Lake Hard Mountains Don’t work problems Don’t Listen Don’t read material Rt 321 You are here. . . Skip Class Unhappyham

Genetics. . . the study of heredity and variation. The most powerful tool in Genetics. . . the study of heredity and variation. The most powerful tool in the biologist’s toolbox. Not just for biologists, - societal, - personal.

Classical Genetics eucaryotic. . . the transmission of the primary hereditary material, Genes DNA Classical Genetics eucaryotic. . . the transmission of the primary hereditary material, Genes DNA Chromosomes Genomes

DNA Nucleotides “Bases” DNA Nucleotides “Bases”

Chromosomes Long Polymers Phosphodiester Bonds Backbone Hydrogen Bonds Double Helix Chromosomes Long Polymers Phosphodiester Bonds Backbone Hydrogen Bonds Double Helix

Genome. . . haploid chromosome component of an organism, • human (23), 3 Gb, Genome. . . haploid chromosome component of an organism, • human (23), 3 Gb, • fruit fly (4), 120 Mb, • nematode (5), 100 Mb, • mustard (5), 120 Mb, • yeast (16), 12 Mb, • bacteria, (1), ~5 -15 Mb. chromosome ~ 5 - 150 Mb long

Organization Units of Heredity Genome chromosome: DNA (Mb) proteins DNA (Mb - Gb) proteins Organization Units of Heredity Genome chromosome: DNA (Mb) proteins DNA (Mb - Gb) proteins gene DNA (kb) promoter: controls expression structural: codes for a protein

Transmission of Hereditary Materials (meiosis/sex) . . . Meiosis: the process of two consecutive Transmission of Hereditary Materials (meiosis/sex) . . . Meiosis: the process of two consecutive cell divisions in the diploid progenitors of sex cells.

Meiosis Cell Biology Genetics . . . the mechanism, timing and steps of cell Meiosis Cell Biology Genetics . . . the mechanism, timing and steps of cell division, …a major result of cell division is the partitioning of DNA, …how a cell divides, …transmission of genomes, …growth and repair. …via the transmission of chromosomes.

Chromosomes …self-replicating genetic structures. • two copies of each chromosome are present at some Chromosomes …self-replicating genetic structures. • two copies of each chromosome are present at some stage of an eukaryotic organism’s life cycle, – haploid: cells carrying one full set of chromosomes, – diploid: cells carrying two full sets of chromosomes, • n = number of haploid chromosomes. • 2 n = number of chromosomes in a diploid organism.

Haploid n=2 (sex cells) Chromosome I 2 n = 4 Chromosome II homologous chromosomes Haploid n=2 (sex cells) Chromosome I 2 n = 4 Chromosome II homologous chromosomes Diploid (somatic cells) homologous chromosomes Chromosome II

Homologous Chromosomes …a pair of chromosomes containing the same linear gene sequence, each derived Homologous Chromosomes …a pair of chromosomes containing the same linear gene sequence, each derived from one parent, – homologous chromosomes carry the same complement of genes, – the DNA sequence of the genes on homologous chromosomes may differ, • alleles: genes at the same location (locus) on homologous chromosomes, but that have different DNA sequences.

Alleles A- Alternative forms of the same gene. a. Heterozygous B- b- C- C- Alleles A- Alternative forms of the same gene. a. Heterozygous B- b- C- C- Homozygous Alleles occur at the same locations (loci) on homologous chromosomes.

Meiosis Homologous Chromosomes S: synthesis of DNA, chromosomes are replicated. Haploid Cell Diploid Cell Meiosis Homologous Chromosomes S: synthesis of DNA, chromosomes are replicated. Haploid Cell Diploid Cell

Synthesis A- -A represents gene A, from one parent. a- -a B- b- -B Synthesis A- -A represents gene A, from one parent. a- -a B- b- -B Homologous Chromosomes -b represents the same gene from the other parent, codes for the ~same protein, may have a slightly different DNA sequence.

Chromosome Structure (cartoons) sister chromatids M phase …after replication. centromere: region of the chromosome Chromosome Structure (cartoons) sister chromatids M phase …after replication. centromere: region of the chromosome where chromatids attach. sister chromatids

Meiosis S: synthesis of DNA, chromosomes are replicated. M: meiosis ( two divisions) after Meiosis S: synthesis of DNA, chromosomes are replicated. M: meiosis ( two divisions) after one synthesis. Haploid Cell Diploid Cell

Meiosis Prophase I … Synapsis: the highly specific parallel alignment of homologous chomosomes during Meiosis Prophase I … Synapsis: the highly specific parallel alignment of homologous chomosomes during the first division of meiosis, A A a a …tetrad: the two homologous chromosomes become attached along their length in a structure termed a tetrad. B B b b

Chiasmata Chiasmata

Meiosis Prophase I cont. A a B B b b Crossing Over: rearranges the Meiosis Prophase I cont. A a B B b b Crossing Over: rearranges the genes from each parent.

Meiosis Metaphase I -- Telophase I A a Aa B B b b A Meiosis Metaphase I -- Telophase I A a Aa B B b b A a B B b b

Meiosis Prophase II -- Telophase II Aa a. A BB no DNA synthesis bb Meiosis Prophase II -- Telophase II Aa a. A BB no DNA synthesis bb a A A a B B b b

Meiosis is critical for sexual reproduction in all diploid organisms. . . meiosis leads Meiosis is critical for sexual reproduction in all diploid organisms. . . meiosis leads to the formation of gametes, – gametes (one from each parent) conjugate to form a zygote, . . . meiosis is the basis for extensive variation among members of a population.

Genetic Recombination I Crossing over. Genetic Recombination I Crossing over.

Genetic Recombination II I-A I-a II-b II-B 2 n combinations of chromosomes, n = Genetic Recombination II I-A I-a II-b II-B 2 n combinations of chromosomes, n = haploid number of chromosomes. I-A II-b I-A II-B I-a II-b Random Assortment of Chromosomes. II-B

2 n combinations of chromosomes n = number of chromosomes • • n n 2 n combinations of chromosomes n = number of chromosomes • • n n = 1, = 2, = 3, = 5, 2 n = 2 2 n = 4 2 n = 8 2 n = 32 Arabidopsis n = 23, 2 n = 8, 388, 608 H. sapiens n = 39, 2 n = yip! dog

Mendelian Genetics • Gregor Mendel (1822 -1884), • Augustinian monk, » Botanist, • Pisum Mendelian Genetics • Gregor Mendel (1822 -1884), • Augustinian monk, » Botanist, • Pisum sativa, • Garden pea, » 1 st “Model System”.

Model Systems • Modern Biology depends largely on the ability to study simple organisms, Model Systems • Modern Biology depends largely on the ability to study simple organisms, and then apply the resulting principles to more complex systems, – i. e. , ask simple questions about immensely complex processes, – the answers are often simple, though not obvious.

Model Organisms • Ease of cultivation, • Rapid Reproduction, • Small size, • Fecund Model Organisms • Ease of cultivation, • Rapid Reproduction, • Small size, • Fecund (large brood size), • Mutants are available and easy to identify, • Broad literature and experimental background available.

Model Organisms organism aka n # genes E. coli S. cereviisae C. elegans Drosophila Model Organisms organism aka n # genes E. coli S. cereviisae C. elegans Drosophila Arabidopsis M. musculus bacteria yeast roundworm fruit fly dicot plant mouse NA 16 5 40 4, 377 5, 770 19, 000 13 379 25, 498 100, 000 25, 000 - 40, 000? H. sapiens human 23 100, 000 25, 000 -40, 000? P. sativum pea 7 ~26, 0 , 000 20, 000 - 25, 000?

General Cell Function ECOCYC General Cell Function ECOCYC

Cell Cycle ~400 of 6022 Saccharomyces cerevisiae genes are active in conjunction with the Cell Cycle ~400 of 6022 Saccharomyces cerevisiae genes are active in conjunction with the cell cycle.

Model Organisms organism aka n # DNA bases E. coli S. cereviisae C. elegans Model Organisms organism aka n # DNA bases E. coli S. cereviisae C. elegans Drosophila Arabidopsis M. musculus bacteria yeast roundworm fruit fly dicot plant mouse NA 16 5 40 4, 639, 675 12, 495, 682 100 Mb 120 Mb H. sapiens human 23 3 Gb P. sativum pea 7 5 Gb Genome Sizes

Genomics DNA: Reagent for the 21 st Century “Biology is in the midst of Genomics DNA: Reagent for the 21 st Century “Biology is in the midst of an intellectual and experimental sea change. . . . essentially the discipline is moving from being largely a data-poor science to becoming a data-rich science. ” Vukmirovic and Tilghman, Nature 405, 820 -822 (2000)

Ø > 206 Gb (Dec. 2007) Ø > 165, 000 organisms Presently Ø > 206 Gb (Dec. 2007) Ø > 165, 000 organisms Presently

Reference, GOLD Reference, GOLD

Genomics • The systematic study of genomes that begins with large scale DNA sequencing Genomics • The systematic study of genomes that begins with large scale DNA sequencing (Structural Genomics), – Functional genomics: how particular DNA sequences facilitate biological functions, – Comparative Genomics: differences between individuals, differences between species, etc. – Bioinformatics: computational discipline that has evolved to handle modern biological data. . .

Post Genomics Era Genetic Testing Drug Discovery Prostate Cancer, KLF 6 Anti-Plasmodium (malaria) Hypertension, Post Genomics Era Genetic Testing Drug Discovery Prostate Cancer, KLF 6 Anti-Plasmodium (malaria) Hypertension, WNK Kinases Breast Cancer, BCR-ABL Alzheimer’s, linked to Chr. 10 …lots of others. Gene Therapy Blindness: Leber congenital amaurosis Parkinson’s: GABA receptor Skin Cancer: T-Cell lymphocytes

More Genomics Environmental/ Ecological Bt Toxin Resistance Metagenomics Dietary studies of scat. Fundamental Research More Genomics Environmental/ Ecological Bt Toxin Resistance Metagenomics Dietary studies of scat. Fundamental Research -Baxter, IR, Young, JC, Armstrong, G, Fosters, N, Bogenschutz, N, Cordova, T, Peer, WA, Hazen, SP, Murphy, A, Harper, JF. (2005) A plasma membrane H+-ATPase is required for the formation of proanthocyanidins in the seed coat endothelium of Arabidopsis thaliana. PNAS, 102 (7): 2649– 2654 - Robertson WR, Clark K, Young JC, Sussman MR. (2004) An Arabidopsis thaliana Plasma Membrane Proton Pump Is Essential for Pollen Development. Genetics. 168(3): 1677 -87

Online Mendelian Inheritance In Man OMIM http: //www. ncbi. nlm. nih. gov/entrez/query. fcgi? db=OMIM Online Mendelian Inheritance In Man OMIM http: //www. ncbi. nlm. nih. gov/entrez/query. fcgi? db=OMIM Bioinformatics

Post-Genomics Biology “The new paradigm, now emerging, is that all genes will be known Post-Genomics Biology “The new paradigm, now emerging, is that all genes will be known (in the sense of being resident in databases available electronically), and that the starting point of a biological investigation will be theoretical. ” - Walter Gilbert Nobel Laureate, Chemistry DNA Science

"I guess there's cool stuff about science, " Watanabe continued, "like space travel and bombs. But that stuff is so hard, it's honestly not even worth the effort. "

Friday • Turn in take home quiz, beginning of class, • Read Chapter 1, Friday • Turn in take home quiz, beginning of class, • Read Chapter 1, and review Chapter 3 if you are at all shaky with meiosis.