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The Human Genome Project:
Impact on Human Health
Pragna Patel, Ph.D.
Institute for Genetic Medicine
University 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
Atcgtacgtaggtcagttt
accggtaccatgtatagg
tacccgggtaccctaccc
Chromosome
T
cggcacc Agcatca
tataggacacatactgat
catgcattacggatcgta
cgtaggtcagtttaccggt
accatgtataggtacccg
ggtaccctacccgggga
atcgtacgtaggtcagttt
accggtaccatgtatagg
tacccgggtaccctaccc
A
Gene
cggcacc
agcatca
tataggacacatactgat
catgcattacggatcgta
cgtaggtcagtttaccgg
accatgtataggtacccg
ggtaccctacccaggga
Normal
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
Establish
Function and
Disease Mechanism
Drug
Candidates
Cure
Genetic Mapping,
Mutation Detection
Diagnostics/
Prognostics
Gene Therapy
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
Linkage
I.
1
II.
1
2
A
N
A
N
A
N
a
D
B
B
b
B
2
3
4
5
6
A
N
a
D
A
N
A
N
A
N
a
D
A
N
A
N
A
N
A
N
A
N
a
D
B
B
B
b
B
b
B
B
B
b
B
B
FINE MAPPING AND MUTATION IDENTIFICATION
Post-genome era
1-5 Million base pairs
…..CGACCGGTATGCGATGACTGGTCATGTACTTACTATTC….
Human genome
sequence
Gene content map
Gene
Normal
.......C C T A C.........
Patient
.......C T T A C.........
DNA sequence
Cumulative Pace of Monogenic Disease Gene
Discovery: 1981 - 2008
PCR HGP
Draft sequence
Impact of Human Genome Project (HGP)
Disease
Pre- HGP
Friedreich ataxia
13 years
Huntington disease
10 years
Spinocerebellar
ataxia type 1
7 years
Post-HGP
Molar hypodontia
<2 months
Congenital tufting
enteropathy
<2 months
Current Status of DNA testing for
single gene disorders
Directory of International Testing Laboratories
www.genetests.org
575 Clinical and research laboratories
1115 Inherited diseases