<p> Date Topic 1 September 29 Lecture: Mouse Genomic facts, strains, crosses, 2 October 1 Lecture: Mapping genes 3 October 3 Paper discussion: Mapping the Clock gene (I) 4 October 6 Paper discussion: Mapping the Clock gene (II) 5 October 8 Paper discussion: Complex trait mapping 6 October 10 Paper discussion: Congenics 7 October 13 Lecture: Transgenics / Knock outs 8 October 15 Paper discussion: The mouse genome project A presentation project must have been selected by each student and approved by LM 9 October 17 Paper discussion: Comparative genomics 10 October 20 Paper discussion: Inducible transgenes 11 October 22 (to Paper discussion: The mouse genome project. Database </p><p> be rescheduled demonstration </p><p> or self-taught) 12 October 24 Paper discussion: Inducible tissue-specific knock-outs 13 October 27 Paper discussion: Genetics modifiers 14 October 29 Paper discussion: ENU mutagenesis 15 October 31 Student presentations</p><p>1 Recommended textbook: Lecture: Mouse Genetics: concepts and applications, by Lee M. Silver, 1995, Oxford University Press The book is out of print. The text is on-line at http://www.informatics.jax.org/silver/</p><p>Class Required reading 1 Silver: Chapters 1, 3.1, 3.2, 3.4, 5.1. 2 Silver: Chapters 7, 8.3.6, 9.3 – 9.5 3 Review: Takahashi J.S. et al. Forward and reverse genetic approaches to behavior in the mouse. Science, 264: 1724-33 (1994). Vitaterna M.H. et al. Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science 264: 719-725 (1994)</p><p>4 King D.P. et al. Positional cloning of the mouse circadian Clock gene. Cell, 89: 641-653 (1997). Antoch M.P., et al. Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell, 89: 655-667 (1997).</p><p>5 Review: Doerge R.W. Mapping and analysis of quantitative trait loci in experimental populations. Nature Rev. Genetics 3: 43-52 (2002). http://www.nature.com/cgi- taf/DynaPage.taf?file=/nrg/journal/v3/n1/full/nrg703_fs.html&filetype=PDF Glazier A.M., Nadeau J.H., Aitman T.J. Finding genes that underlie complex traits. Science, 298: 2345-2349 (2002). http://www.sciencemag.org/cgi/reprint/298/5602/2345.pdf http://www.sciencemag.org/cgi/data/298/5602/2345/DC1/1 Todd J.A., et al. Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature, 351: 542-6 (1991). Penha-Goncalves C. et al. Identification of a structurally distinct CD101 molecule encoded in the 950-kb Idd10 region of NOD mice. Diabetes, 52: 1551-1556 (2003). http://diabetes.diabetesjournals.org/cgi/reprint/52/6/1551.pdf 6 Wakeland E.K. et al. Speed congenics: A classic technique moves into the fast lane (relatively speaking). Immunol. Today, 18: 473-7 (1997). http://www.sciencedirect.com/science? _ob=MImg&_imagekey=B6VHW-3WJDW3Y-7- 1&_cdi=6077&_orig=browse&_coverDate=10%2F31%2F1997&_sk=999819989&view=c&wchp=dGLbVlb- zSkWb&_acct=C000010879&_version=1&_userid=130901&md5=e1764bac755e54ab3f9b997b1b292a6e&ie =f.pdf Markel P. et al. Theoritical and empirical issues for marker-assisted breeding of congenic mouse strains. Nat. Genetics, 17: 280-84 (1997) 7 Transgenics and knock-outs lecture 8 Review:</p><p>2 Green E.D. at al. Strategies for the systematic sequencing of complex genomes. Nature Rev. Genetics, 2: 573-583 (2001). http://www.nature.com/cgi-taf/DynaPage.taf? file=/nrg/journal/v2/n8/full/nrg0801_573a_fs.html&filetype=PDF Mouse Genome Sequencing consortium. Initial sequencing and comparative analysis of the mouse genome. Nature, 420: 520-562 (2002). http://www.nature.com/cgi-taf/DynaPage.taf? file=/nature/journal/v420/n6915/full/nature01262_fs.html&content_filetype=PDF</p><p>The FANTOM Consortium and the Riken Genome Exploration Research Group Phase I & II team. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature, 420: 563-573 (2002). http://www.nature.com/cgi-taf/DynaPage.taf? file=/nature/journal/v420/n6915/full/nature01266_fs.html&content_filetype=PDF 9 Review: Nadeau J.H., Sankoff D: Counting on comparative maps. Trends Genet., 14:495-501 (1998). http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TCY-3VCVF0D-C- 5&_cdi=5183&_orig=browse&_coverDate=12%2F01%2F1998&_sk=999859987&view=c&wchp=dG LbVzz- zSkWz&_acct=C000010879&_version=1&_userid=130901&md5=be51dd8058ac8b87f3301fae1f6f63 0f&ie=f.pdf</p><p>Ureta-Vidal A. et al. Comparative genomics: Genome-wide analysis in metazoan eukaryotes. Nature Rev. Genetics, 4: 251-262 (2003). http://www.nature.com/cgi- taf/DynaPage.taf?file=/nrg/journal/v4/n4/full/nrg1043_fs.html&filetype=PDF</p><p>Gregory, S. G., et al. A physical map of the mouse genome. Nature, 418:743-750 (2002). http://www.nature.com/cgi-taf/DynaPage.taf? file=/nature/journal/v418/n6899/full/nature00957_fs.html&content_filetype=PDF Thomas J.W. et al. Comparative analyses of multi-species sequences from targeted genomic regions. Nature, 424: 788-793 (2003). http://www.nature.com/cgi-taf/DynaPage.taf? file=/nature/journal/v424/n6950/full/nature01858_fs.html&content_filetype=PDF 10 Review: Lewandoski, M. Conditional control of gene expression in the mouse. Nature Rev. Genetics, 2: 743-755 (2001). http://www.nature.com/cgi-taf/DynaPage.taf? file=/nrg/journal/v2/n10/full/nrg1001-743a_fs.html&filetype=PDF Shin, M.K. et al. The temporal requirement for endothelin receptor-B signaling during neural crest development. Nature, 402: 496-501 (1999). http://www.nature.com/cgi- taf/DynaPage.taf?file=/nature/journal/v402/n6761/full/402496a0_fs.html&content_filetype=PDF Wang X. L. et al. Development of gene-switch transgenic mice that inducibly express TGFbeta1 in the epidermis. Proc. Natl. Acad. Sci., 96: 8483-8488 (1999). http://www.pnas.org/cgi/reprint/96/15/8483.pdf 11 Hand-on session: using mouse genomic databases</p><p>Varmus H. Genomic empowerment: The importance of public database. Nat. Genetics Supplement, p. 3, (Sept. 2002). http://www.nature.com/cgi-taf/DynaPage.taf?</p><p>3 file=/ng/journal/v32/n1s/full/ng963.html&filetype=pdf</p><p>Tutorials: Nature Genetics Supplement, September 2002.</p><p>Question 1: How does one find a gene of interest and determine that gene's structure? Once the gene has been located on the map, how does one easily examine other genes in that same region? pp 9 – 17. http://www.nature.com/cgi-taf/DynaPage.taf? file=/ng/journal/v32/n1s/full/ng966.html&filetype=pdf</p><p>Question 7: How would an investigator easily find compiled information describing the structure of a gene of interest? Is it possible to obtain the sequence of any putative promoter regions? http://www.nature.com/cgi-taf/DynaPage.taf? file=/ng/journal/v32/n1s/full/ng972.html&filetype=pdf</p><p>Question 12: How does a user find characterized mouse mutants corresponding to human genes? http://www.nature.com/cgi-taf/DynaPage.taf? file=/ng/journal/v32/n1s/full/ng977.html&filetype=pdf</p><p>Question 13: A user has identified an interesting phenotype in a mouse model and has been able to narrow down the critical region for the responsible gene to approximately 0.5 cM. How does one find the mouse genes in this region? http://www.nature.com/cgi- taf/DynaPage.taf?file=/ng/journal/v32/n1s/full/ng978.html&filetype=pdf 12 Meyers, E. N. et al. An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination. Nat. Genetics, 18: 136-141 (1998). Tannour-Louet, M. et al. A tamoxifen-inducible chimeric Cre recombinase especifically effective in the fetal and adult mouse liver. Hepatology, 35: 1072-1081 (2002). 13 Review: Nadeau, J.H. Modifier genes in mice and humans. Nature Rev. Genetics, 2: 165- 174 (2001). http://www.nature.com/cgi-taf/DynaPage.taf? file=/nrg/journal/v2/n3/full/nrg0301_165a_fs.html&filetype=PDF Bonyadi M. et al. Mapping of a major genetic modifier of embryonic lethality in TGF beta 1 knockout mice. Nat. Genetics, 15: 207-11 (1997) Gould K.A., et al. Genetic evaluation of candidate genes for the Mom1 modifier of intestinal neoplasia in mice. Genetics, 144:1777-85 (1996)</p><p>14 Nelms, K.A., and Goodnow, C.C. Genome-wide ENU mutagenesis to reveal immune regulators. Immunity, 15: 409-18 (2001). http://download.immunity.com/pdfs/1074- 7613/PIIS1074761301001996.pdf</p><p>Papathanasiou, P. et al. Widespread Failure of Hematolymphoid Differentiation Caused by a Recessive Niche-Filling Allele of the Ikaros Transcription Factor. Immunity, 19: 131-144 (2003). http://download.immunity.com/pdfs/1074-7613/PIIS1074761303001687.pdf Chen, Y. et al. Genotype-based screen for ENU-induced mutations in mouse embryonic</p><p>4 stem cells. Nat. Genetics, 24: 314-317 (2000). http://www.nature.com/cgi-taf/DynaPage.taf? file=/ng/journal/v24/n3/full/ng0300_314.html&filetype=pdf Munroe, R.J. et al. Mouse mutants from chemically mutagenized embryonic stem cells. Nat. Genetics, 24: 318-321 (2000). http://www.nature.com/cgi-taf/DynaPage.taf? file=/ng/journal/v24/n3/full/ng0300_318.html&filetype=pdf</p><p>5</p>