Genomics

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Genomics

• A Systematic Study of the Locations, Functions
  and Interactions of Many Genes at Once

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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

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Size of the Human Genome
Per haploid genome
New estimate 32,000 genes
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Structural Genomics Maps

• Genetic Maps (Linkage Maps)
• Gene locations relative to other known genes
• Based on recombination, measured in centimorgans
• Physical Maps
• Gene distances measured in numbers of base pairs
• Based on direct analysis of DNA

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Increasing Resolution of Maps
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Mapping of Restriction Fragments
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Solution
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Two Sequencing Approaches for the Human Genome
Project
Contiguninterrupted stretch of genome derived
from two or more partially overlapping cloned DNAs
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Other Sequencing Discoveries

• Single-Nucleotide Polymorphisms
• Single-base-pair differences between individuals
  of the same species
• Used to study disease-causing genes
• Expressed-Sequence Tags
• cDNA fragments produced from RNA of a specific
  cell type
• Used to study gene activity

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Applying Your Knowledge

1. Physical Map
2. Sequence Map
3. Genetic Map
4. None of these is correct.

• Which type of map
• Is based on recombination frequencies?
• Presents the order of the nucleotides in the DNA?
  
• Shows the number of nucleotides between regions
  on the map?

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Genomic DNA
Transcriptome
Proteome
DATABASE
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Functional Genomics Microarray Analysis

• Microarray
• DNA sequences arranged in a matrix
• Tests for binding to complementary sequences

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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.
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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

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Building specific oligonucleotides for
microarray analysis
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Array of 1046 cDNAs probed with bone marrow based
cDNA probe
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Applying Structural Genomics Identifying
Genotypes at the Molecular Level
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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
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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 30-40 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
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Applying Your Knowledge

1. Southern Blot
2. Sanger DNA Sequencing
3. Northern Blot
4. Microarray Analysis

• Which method would be best for determining
  whether
• Sequences on two genomic clones overlap?
• A thyroid cancer cell is producing different
  proteins from a non-cancerous thyroid cell?
• The size of a mRNA for a specific gene sequence?

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Bioinformatics
Bioinformatics is an information science focused
on -storage of genetic data -organization of
data -indexing sequence information
Ask me about summer internships in Bioinformatics
at NIST!
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Applications of Bioinformatics

• DNA
• -identifying gene sequences
• -predicting protein sequences
• -exploring evolutionary relationships
• Protein
• -identifying protein products of genes

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Databases
DNA GenBank(links to protein sequences, scientific literature and genetic information)http//www.ncbi.nlm.nih.gov80/
Restriction Sites WebCutterhttp//www.firstmarket.com/cutter
Protein ExPASy Expert Protein Analysis System http//www.expasy.ch/