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