The Human Genome Project: Impact on Human Health

							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

                            T
                    cggcacc Agcatca
                                          Normal
     Chromosome     tataggacacatactgat
                    catgcattacggatcgta
                    cgtaggtcagtttaccggt
                    accatgtataggtacccg
                    ggtaccctacccgggga



                    atcgtacgtaggtcagttt
                    accggtaccatgtatagg
                    tacccgggtaccctaccc

                    cggcacc A  agcatca
                                          Patient
                    tataggacacatactgat

        Gene        catgcattacggatcgta
                    cgtaggtcagtttaccgg
                    accatgtataggtacccg
                    ggtaccctacccaggga
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                         Genetic Mapping,
Genome
               Find Genes        Mutation Detection



             Establish               Diagnostics/
             Function and            Prognostics
             Disease Mechanism


Drug
Candidates
                    Cure          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                         2

                         A   A                 A           a
                         N   N                 N           D




                         B   B                 b           B




   II.
             1       2            3                4               5       6


         A   a   A   A       A    a        A       A           A   A   A   a
         N   D   N   N       N    D        N       N           N   N   N   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


                                                Human genome
  …..CGACCGGTATGCGATGACTGGTCATGTACTTACTATTC….
                                                sequence

                                                Gene content map

                                                Gene




     Normal      .......C C T A C.........
                                                 DNA sequence
     Patient     .......C T T A C.........
Cumulative Pace of Monogenic Disease Gene
          Discovery: 1981 - 2008




             PCR HGP         Draft sequence
    Impact of Human Genome Project (HGP)

       Disease       Pre- HGP     Post-HGP



Friedreich ataxia    13 years
Huntington disease   10 years
Spinocerebellar      7 years
  ataxia type 1


Molar hypodontia                  <2 months
Congenital tufting                <2 months
  enteropathy
    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