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The Human Genome Project: Impact on Human Health
Pragna Patel, Ph.D.Institute for Genetic MedicineUniversity of Southern California
Variation in DNA sequence can be “silent” or lead to disease
DNA Genetic Code dictates amino acid identity in a protein
Variation in DNA sequence in gene can change the protein produced by the Genetic Code
Types of Inherited Human Diseases
• Single gene disorders – rare, familial (Eg. Hemophilia)
• Chromosomal abnormalities – typically sporadic (Eg. Down’s syndrome)
• Multifactorial disorders (Eg. Arthritis, diabetes) -Several genes involved, complex
inheritance- Environmental factors
Human chromosomes
Challenge of discovering a mutation in the genome
Genome
Chromosome
Gene
Atcgtacgtaggtcagtttaccggtaccatgtataggtacccgggtaccctaccc
cggcaccTAgcatca
tataggacacatactgatcatgcattacggatcgtacgtaggtcagtttaccggtaccatgtataggtacccgggtaccctacccgggga
Normal
atcgtacgtaggtcagtttaccggtaccatgtataggtacccgggtaccctaccc
cggcaccAagcatca
tataggacacatactgatcatgcattacggatcgtacgtaggtcagtttaccggaccatgtataggtacccgggtaccctacccaggga
Patient
Goals of the Human Genome Project (1990)
• Identify all the genes in human DNA (now estimated at ~25,000)
•Determine the sequence of 3 billion chemical base pairs that make up human DNA
•Determine the sequence of model organisms for comparison to human DNA sequence
Goals of the Human Genome Project (1990)
• Store the information in databases •Improve tools for data analysis
•Transfer related technologies to the private sector
•Address the ethical, legal, and social issues (ELSI) that may arise from the project
The Human Genome Project: Why?
Sequence Genome
Find Genes
EstablishFunction andDisease Mechanism
Genetic Mapping,Mutation Detection
DrugCandidates Gene Therapy
Diagnostics/Prognostics
Cure
Requisites for genetic mapping of a disease to a chromosome
1. Families with the disease
2. Accurate diagnosis
3. Defined pattern of inheritance
4. Polymorphic DNA markers
Tracking a disease mutation-bearing chromosome in a family
I.AN
B
AN
B
1 2
AN
b
aD
B
1 32 4 5 6
AN
B
aD
B
AN
B
AN
b
AN
B
aD
b
AN
B
AN
B
AN
B
AN
b
AN
B
aD
B
Linkage
II.
FINE MAPPING AND MUTATION IDENTIFICATION Post-genome era
Gene
Normal
Patient
.......C C T A C.........DNA sequence
.......C T T A C.........
Human genome sequence
…..CGACCGGTATGCGATGACTGGTCATGTACTTACTATTC….
Gene content map
1-5 Million base pairs
Cumulative Pace of Monogenic Disease Gene Discovery: 1981 - 2008
2008
Draft sequencePCR HGP
Impact of Human Genome Project (HGP)
Disease Pre- HGP Post-HGP
Friedreich ataxia 13 years
Huntington disease 10 years
Spinocerebellar ataxia type 1
7 years
Molar hypodontia <2 months
Congenital tufting enteropathy
<2 months
Current Status of DNA testing for single gene disorders
Directory of International Testing Laboratories Directory of International Testing Laboratories www.genetests.orgwww.genetests.org
575 Clinical and research laboratories
1115 Inherited diseases