What is the Human Genome Project

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Celera Genomics
Public Consortium
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Sequence Genomes
Genetic Mapping, Mutation Detection
Find Genes
Establish Function and Disease Mechanism
Diagnostics/ Prognostics
Drug Candidates
Gene Therapy
Cure
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Sequence the 3 billion () base pairs of human
DNA and identify all genes contained in the human
genome
DNA Sequence Reads - Need 60,000,000 of them!!
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Time Line of the Human Genome Project
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BCM-HGSC Sequencing Throughput
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Standard Molecular Biology techniques running
agarose gels.
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CS-Packard DNA Production Robotic Systems (x 3)
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Multiplexed (104) Capillary Array for
Electrophoresis
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State of the Art - ABI 3700 Prism DNA Sequencer
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US 300,000 Each!
A room full of 3700 Sequencers total price tag
of US 22.5 Million
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State of the Art Assembly
Whole Genome Shotgun (WGS)
BAC by BAC
Versus
-Front end loaded, - Tractable Assembly
Problem
-Efficient front end, - Huge Assembly Problem
BCM- HGSC
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Linux Farm
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Very small changes in technology have had a huge
impact on the HGP.. Imagine what a large
change in technology would do
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The Future More Genomes!!
Rat, Mouse, Rabbit, Dog, Chimp, Rhesus,
Zebrafish, Fugu, Hamster, Cow, Sheep, Pig,
Chicken, Honey Bee, Silk Worm, Shark, Dolphin,
Whale, Frog, Sea Urchin, Sea Squirt, Sea Turtle,
Salmon, Hydra, Wallaby, Platypus, Rice, Wheat,
Maize, Sorgum, Soy, Banana, Poplar, Potato,
Corn, Sea Turtle, Wheat, Pine .
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COMPLETE (HETEROZYGOUS) MUTATION DETECTION
ABI 370 Universal Primer Tag PCR
exon
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OMIM - 10,000 Entries
BCM- HGSC
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Dextrocardia and Situs Inversus
Disorders of laterality occur in 2 3 per 10,000
live births
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BCM- HGSC
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SCREENING 160 SPORADIC PATIENTS IN NODAL
SIGNALING PATHWAY
NODAL LEFTYA competing for receptor components
RECEPTORSTYPE 1 (ALK2 ACVR1ALK4 ACVR1B
ALK7 (mouse) TYPE 2 (ActRIIA ACVR2ActRIIB
ACVR2b)
EGF-CFC Co-Factor Proteins Cripto and
Cryptic Interacts with ALK4 receptor
INTRACELLULAR MEDIATORS, SMAD2, SMAD3, SMAD4
SMADS INTERACTS w/FAST1 to activate gene
SMADS INTERACTS w/TGIF to repress pathway
Human mutations in all loci marked in read
Target Genes PITX2 NODAL LEFTYB
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Epigenetics/Methylation
Epigenix web site
Genomic DNA can be different in Different cells
of the same person..
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230 Personnel
BCM-HGSC