BiologyDept. |
BIO 290Genomics
|
|
BiologyDept. |
BIO 290Genomics
|
|
Texts: A Primer of Genome Science by Greg Gibson & Spencer V. Muse. 2002. Sinauer Associates, Inc., Publishers Applied Molecular Genetics by Roger L. Miesfeld. 1999. Wiley-Liss publishers Recommended Supplements: (1) Introduction to bioinformatics by T.K. Attwood & D.J. Parry-Smith. 1999. Addison Wesley Longman Publishers. (2) "Trends Guide to Bioinformatics: Database Searching, Sequence alignment, Gene finding, Functional Genomics, Protein Classification, Phylogenies." Trends Supplement, 1998. Elsevier Publishers. (3) An excellent text for learning the programming language, Perl (Practical extraction and report language), an ideal language for biological data analysis: oreilly.com -- Online Catalog Beginning Perl for Bioinformatics |
| Bio 290 Genomics and Bioinformatics: An introduction to the structural properties,
functional dynamics, and genetic architectures of genomes from a diverse
selection of model organisms, ranging from microbes to humans.
Scientists analyze these
genomes by both molecular genetic techniques and
bioinformatics, including proteomics. A major topic is the Human
Genome Project and its implications for treating human diseases; a
central theme of the course is the development and analysis of
evolutionary relationships among diverse organisms, including humans.
Prerequisites: BIO 120 and BIO 140;
recommended: BIO 220 and CHEM
120.
All students enrolled in this course have heard my many references to "structure, function, organization, and evolution." Now add "sequence" to the start of the list, and insert "genomics" before evolution to generate: "sequence, structure, function, organization, genomics, evolution." In this course, we will sort out, discuss, and analyze the relationships and implications of the terms in this new list. Adding "sequence" and "genomics" to the standard list creates a modern, state-of-the-art, Molecular Biological focus. One of the "Primary Directives" of modern Genetics remains the same: to determine the relationship of the genotype to the phenotype. Now with the advent of Genomics and Bioinformatics, the experimental approaches to fulfilling the Primary Directive are different from those used in the past decades of genetic research. Instead of dissecting a biological process displaying a known phenotype with a battery of mutants paired in all possible cross combinations to determine the number and types of genes responsible for the process, and eventually to isolate the genes in question by recombinant DNA technologies (to get the final genotype, i.e. the gene sequences), modern and future geneticists will start with a gene sequence of unknown function and then proceed to identify and characterize its function and roles in biological processes. In other words, modern geneticists start with the genotype and work towards elucidating the phenotype, and how that phenotype is produced by local and global gene expression interactions and patterns. The new DNA and protein technologies include "knock-out" mutants, microarrays on DNA chips, protein interaction assays, sophisticated microscopic methods to locate expressed proteins. One common experimental approach underlies all these different, biochemical and genetic techniques: Bioinformatics! The Goal is not only to know all the gene sequences in many organisms, but also to understand all the genes' functions in all these organisms, and how all the genes interact locally to produce a phenotype, and how they interact globally to explain the similarities and differences observed in the great, wonderful diversity of life. Genomics (structural, functional, and comparative -- see below) with Bioinformatics will lead the way to answering these genotype/phenotype questions. Pre-requisites: BIO 120 and BIO 140 half courses; recommended: one semester of chemistry, and BIO 220; or permission of instructor. click here for all course registration information. |
| Genomics
is rapidly becoming a multifaceted sub-discipline of biology, and aims
to understand: (1)
the molecular organization and (2) information content of the
entire genome (= the collection of all the
genes in a gamete, or the haploid set of chromosomes) and its gene
products (the transcriptome and proteome
-- see below).1 Genomics
includes the development and application of new mapping, sequencing, and
computational procedures for the (molecular) analysis of the entire
genome.2 Genomics
has 3 distinct subfields: (a) Structural genomics = the genetic and
physical mapping, and sequencing of entire genomes, (b) Functional
genomics = the analysis of gene (and non-gene) sequences, particularly
all those genes that make RNA (mRNA, tRNA, rRNA, snRNA, etc.), or the transcriptome,
and all those genes that make only mRNA for translation into protein, or
the proteome, (c) comparative genomics =
the comparison of entire genomes from different organisms to understand
functional and evolutionary relationships.2
1.
An Introduction to Genetic Analysis by A.J.F. Griffiths, J.H.
Miller, D.T. Suzuki, R.C. Lewontin, and W.M. Gelbart. 2000. Ch. 14, p.
436. W.H. Freeman and Co., Publishers. |
|
Bioinformatics* fuses biology with mathematics (especially statistics) and computer science (algorithms and their implementations in a scripting language like Perl above) to:
"Bioinformatics** is the application of computational tools and techniques to the management and analysis of biological data." *Definition (except for parenthetical phrases) taken from: Genetics
by P.J. Russell. 2002. Glossary, p. 729. Benjamin Cummings,
Publihsers. |
| The lecture portion
of the course serves two purposes:
(1) to introduce you to the basic, core concepts of Genomics as provided by both history and key experiments. How are genomes studied and characterized molecularly? What key experiments led to greater understanding of the structure to function relationships of whole genomes? Which bioinformatic methods reveal and conceptualize the raw information provided by genomics research? (2) to provide you with a solid theoretical basis for not only methodology but also more importantly for hypothesis construction and testing by proper experimental design (i.e., the scientific method used in genomics and bioinformatics).* Every attempt will be made to integrate major concepts to show the unity of the various sub-disciplines comprising molecular biology by applying the knowledge and techniques of genomics and bioinformatics. Every attempt will be made to collect a seemingly overwhelming amount of details into regular, concept-based patterns forming the over-arching themes and principles of modern biology. Yes, these patterns and themes exist! Reductionism will lead to Holism, especially by way of Bioinformatics, and to an increased awareness of how sets of regularly repeating themes and patterns, first observed in macromolecular sequences, combine in myriad ways to generate the wonderful, rich diversity of living organisms. *In other words, together we will try to get at least a glimpse of the subtle variations in relatively simple biological structures, and how these variations combine in numerous ways to contribute to a wonderful and exciting biological complexity and hence diversity. As always with all my courses, the pedagogy rests on two main themes: (1) Knowing, understanding, and analyzing major concepts, and how these concepts relate to each other, to the major concepts of all biology, and to disciplines and ideas outside the normal realm of biological science; (2) Understanding the theory and practice of the scientific method, and then how it transforms questions, observations, problems, etc., into concept and ultimately theory by way of well designed experiments coupled with informed interpretation of the experimental data. A note about your text for this course: a constant, repeating theme throughout the entire book, in each chapter, almost like a fractal image, is the fundamental relationship of structural genomics to functional genomics to comparative genomics, which is interlaced always with Bioinformatic analyses. |
(PGS = A Primer of Genome Science text; AMG = Applied Molecular Genetics text
Review of the Basics I: Molecular
Biology
Review of the Basics II: Recombinant DNA Technology
Chap. |
Topic |
Questions & Problems |
AMG-1 |
Biochemical Basis of Applied
Molecular Genetics: p.3-7, Central Dogma; DNA structure (fig.1.3) p. 12-17, DNA metabolizing enzymes p. 17-22, Biochemical methods to study DNA and RNA |
|
| AMG-4 |
Characterization of Genomic DNA: p. 83-88, Overview of Genome organization in bacteria, yeasts, & humans p. 88-94, Genomic Mapping p. 97-99, Cosmid Vectors, fig. 4.11 p. 99 and 101, BAC vectors, fig. 4.13 |
|
| AMG-9 |
Contemporary Applied Molecular Genetics: p. 244-250, Accessing Molecular Genetic Information through the Internet |
|
Appendix
B,C,D, p.275-280; |
Properties of Nucleic Acids, Properties of Amino Acids, Properties of Common Restriction Enzymes |
|
Useful Internet Resources |
I. Introduction and Overview:
Genomics and Model Organisms;
Methods Survey, basic Bioinformatics.
Chap. 1 |
Topic |
Questions & Problems |
| PGS-1 | p. 1-4, Core
Aims of Genome Science. |
|
II. Structural Genomics & Bioinformatics
Chap. |
Topic |
Questions & Problems |
PGS-2 |
p. 63-76, Automated
DNA sequencing (includes Box. 2.1, p.
72-75) (see also AMG, p.19-20, fig.1.13, p.21; p. 237-238, fig. 9.1, p.239) p. 78-84, Genome Sequencing: Hierarchical p. 84-90, Genome Sequencing: Shotgun (includes Box 2.2, 86-87) p. 90, Sequence Verification p. 91-101, Genome Annotation: EST sequencing, Ab initio gene dis- covery, non-protein coding genes p. 101-105, Structural features of Genome Sequences p. 105-117, Functional Annotation and Gene Family Clusters; note COG's, p. 109-111 with Orthologs and Paralogs |
|
III. Functional Genomics & Bioinformatics: the Transcriptome.
Chap. |
Topic |
Questions & Problems |
PGS-3 |
p.
123-126: cDNA Microarray technology |
IV. Functional Genomics & Bioinformatics: the Proteome.
Chap. |
Topic |
Questions & Problems |
| PGS-4 |
p. 183-188
(without Box 4.1): Web and Internet Sites for comparing and identifying
protein domains p. 188-193: 2D-PAGE, fig. 4.4 p. 202-204: Yeast two-hybrid screens, fig. 4.12 (see also AMG, p. 128-130, and fig. 5.9) p. 204-207: Structural Proteomics and defining a Protein Domain p. 207-209: Protein Structure Determination, fig. 4.14 |
V. The Importance of SNP's: Theory and Practice.
Chap. |
Topic |
Questions & Problems |
PGS-5 |
(to be included in full course) |
VI. Comparative Genomics & Bioinformatics
Chap. |
Topic |
Questions & Problems |
PGS-6 |
(to be included in full course) |
|
Grade categories, distributions, scaling,
and Exam dates: |
|
(A) Bioinformatics: |
(B) Model Organisms:
|
(C) Genomics & Proteomics: |
|
(D) Programs: |
(E) Methods:
|
(F) General/Miscellaneous: |
Links Collections for Specific Tasks in Genomics & Bioinformatics: Protein Motif and Domain Analyses |
