1. Genomics
A Systematic Study of the Locations, Functions and Interactions of Many Genes at Once

2. Genomics Overview Structural Genomics characterizes the
Organization and sequence of the DNA in the whole genome
Functional Genomics characterizes the
Transcriptome: mRNA production as an indicator of gene expression
Proteome: protein production
Comparative Genomics compares the structure and functions of genomes of different organisms

3. Size of the Human Genome
Per haploid
genome
New estimate 32,000 genes

4. Structural Genomics: Maps
Genetic Maps (Linkage Maps)
Gene locations relative to other known genes
Based on recombination, measured in centimorgans or map units
Physical Maps
Gene distances measured in numbers of base pairs
Based on direct analysis of DNA

5. Increasing Resolution of Maps

6. Mapping of Restriction Fragments

7. Solution

8. Map-Based Sequencing Approach for the Human Genome Project
Contig=uninterrupted stretch of genome derived from two or more partially overlapping cloned DNAs

9. Whole-Genome Shotgun Sequencing Approach for the Human Genome Project

10. Other Sequencing Discoveries
Single-Nucleotide Polymorphisms
Single-base-pair differences between individuals of the same species
Can be inherited together in a specific set or haplotype
Used to study disease-causing genes

11. Other Sequencing Discoveries
Expressed-Sequence Tags
Small sequences derived from cDNA fragments produced from RNA of a specific cell type
Act as markers to identify a larger DNA fragment
Used to study gene activity

12. Genomic DNA
Transcriptome
Proteome
DATABASE

13. Functional Genomics: Microarray Analysis
DNA sequences arranged in a matrix
Tests for binding to complementary sequences

14. A cDNA microarray containing 19,200 ESTs was used to identify genes that may be involved in colon tumor metastasis (spreading).
cDNA from a colon tumor with low metastatic activity is labeled green. This shows genes that are down-regulated during metastasis.
cDNA from a colon tumor with high metastatic activity is labeled red. This shows genes that are up-regulated during metastasis.

16. Steps in Microarray Analysis
Arrange DNA or cDNA in an ordered array on a glass slide
(can also build oligonucleotides directly on a slide)
Incubate array with fluorescently-labeled probe
Detect probe hybridization using a laser
Record and store data with computers

17. Building specific
oligonucleotides for
microarray analysis

18. Applying Structural Genomics: Identifying Genotypes at the Molecular Level
Lane 2: Deletion Mutation affecting codon 39
BRCA1 Mutations
Lane 3: Insertion Mutation affecting codon 40

19. Functional Genomics: Studying Gene Expression
Northern Blotting
-separate mRNA from specific cell
type by size using gel electrophoresis
-transfer mRNA to filter
-use DNA probe to detect complementary mRNA sequences

21. Using Human Genome Information
Pharmacogenomics
Using DNA Microarrays to select individual drug treatments
Mutations in Gene for
Affect the following disease conditions
Cytochrome P450
Affects rate of metabolizing drugs
5-10% of Caucasians and African Americans have low rates
Apo E4
Gene dose affects
Age of onset for Alzheimer's disease
Response to drug Tacrine

23. Bioinformatics Bioinformatics is an information science focused on
-storage of genetic data
-organization of data
-indexing sequence information

24. Applications of Bioinformatics
DNA
-identifying gene sequences
-predicting protein sequences
-exploring evolutionary relationships
Protein
-identifying protein products of genes

25. Databases
DNA
GenBank (links to protein sequences, scientific literature and genetic information)
Exons
GenScan
Transcriptome
Unigene
Restriction Sites
WebCutter
Protein
ExPASy= Expert Protein Analysis System