DE isenberg Part 1 by 7L6t10

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									   Genetic Statistic Application in
         Forensic Science

                         Arthur J. Eisenberg, PhD
Professor and Chairman Department of Forensic and Investigative Genetics
            Co-Director UNT Center for Human Identification
                    Institute of Investigative Genetics
             University of North Texas Health Science Center
                          Fort Worth, Texas USA
The Science of DNA for Human Identification
DNA is Responsible for Transmitting
    Hereditary Characteristics
Human Cells Contain Two Kinds of DNA


   Nuclear DNA and Mitochondrial DNA




           *

                              *
The Nucleus Contains 23 Pairs of Chromosomes
DNA in the Cell




          Target Region for PCR
   DNA Amplification with the
Polymerase Chain Reaction (PCR)


                5’                          3’
                5’                          3’
                                                  Starting
                3’                         5’      DNA
                3’                         5’
                                                 Template
                           Separate
                            strands
                          (denature)
      Forward
    5’ primer        3’                    5’                 3’

                          Make copies
                          Add primers
                        (extend primers)
                                                         3’        5’
     3’              5’    (anneal)
                                                         Reverse
                                                          primer
PCR Copies DNA Exponentially through
      Multiple Thermal Cycles
                 Original DNA target region




                       Thermal cycle


                       Thermal cycle

                       Thermal cycle



In 32 cycles at 100% efficiency, 1.07 billion copies
        of targeted DNA region are created
  13 CODIS Core STR Loci
     TPOX

          D3S1358


                                 D8S1179       TH01
                    D5S818
                                                      VWA
               FGA           D7S820
                    CSF1PO



                                               AMEL


D13S317                                           AMEL
                        D18S51
             D16S539                  D21S11
Alleles – Contain Varying Numbers of
          4 Base Pair Repeats



 Allele:

   5       AATG AATG AATG AATG AATG

   6       AATG AATG AATG AATG AATG AATG

   7       AATG AATG AATG AATG AATG AATG AATG



           Flanking region of unique sequence
 Typical DNA Profile

D3S1358   14,16 D13S317      11,12
vWA       14,19 D7S820       10,10
FGA       21, 21 D16S539     12,13
D8S1179   11,15 THO1          7, 9
D21S11    30, 32 TPOX         8,12
D18S51    15,17 CSF1PO       11,13
D5S818    12,12 Ameloginin   X,Y
Multiplex PCR

       •   Over 15 Markers Can Be
           Copied at Once
       •   Sensitivities to levels less than
           1 ng of DNA
       •   Ability to Handle Mixtures and
           Degraded Samples
       •   Different Fluorescent Dyes
           Used to Distinguish STR Alleles
           with Overlapping Size Ranges
 310 Genetic Analyzer
Capillary Electrophoresis
Current CODIS Acceptable Kits
       AmpFlSTR® Identifiler™
       D8S1179          D21S11          D7S820          CSF1PO    6FAM
                                                                  (blue)

                 TH01
   D3S1358                    D13S317       D16S539                VIC
                                                       D2S1338
                                                                 (green)

                                 TPOX
D19S433           VWA                         D18S51
                                                                   NED
                                                                 (yellow)

AMEL      D5S818                 FGA
                                                                   PET
                                                                   (red)

                  GS500 LIZ size standard

                                                                    LIZ
                                                                 (orange)
Current CODIS Acceptable Kits
COMBINED DNA INDEX SYSTEM
          CODIS MISSION

• The FBI Laboratory's Combined DNA Index
    System (CODIS) blends forensic science and
    computer technology into an effective tool
    for providing investigative leads to assist in
    solving crimes.
•   CODIS enables federal, state, and local crime
    labs to exchange and compare DNA profiles
    electronically, thereby linking crimes to each
    other and to convicted offenders, as well as
    in the identification of missing persons and
    human remains.
      What is a Database?

 A database is an organized file or files
 of data that can be searched to retrieve
 information
 DNA databases compare crime scene
 evidence to a database of DNA profiles
 obtained from known individuals to
 provide the Police with investigative
 leads
CODIS ARCHITECTURE

NDIS                       National



  California                 Florida                   Texas




SDIS   CalDOJ                     FDLE
                                                           DPS




LDIS
                 LDIS          LDIS            LDIS
               Tampa, FL   Tallahassee, FL   Orlando, FL
CODIS INDICES
OFFENDER
  Convicted Offenders
  Arrestee
FORENSIC
  Forensic Crime Scene Samples
MISSING PERSONS
  • Unidentified Human Remains
  • Missing Persons Direct Reference Samples
     (baby teeth, tooth brush, hair brush, etc.)
  • Family Reference Samples
                Question 1
     How common or rare is the
        evidence profile?
• This can be calculated by either the random
 match probability (RMP) or by using the
 likelihood ratio (LR) using the Hardy-Weinberg
 Equilibrium Formula.
                 p12 + 2p1p2 + p22 = 1
    A1A 1 = p 12      A1A2 = 2p1p2     A2A2 = p 22
            freq(A1) = p1       freq(A2) = p2
   For homozygous loci, a Theta correction () is used to
          account for population substructure
     Homozygous locus frequency = p2+p(1-p)
PART 2
                  Paternity Exclusion




                        Dual
Obligate allele    Obligate alleles         Obligate allele




X                   X                   X
                  Paternity Exclusion




Obligate allele            Obligate allele Obligate allele   Obligate allele




X                           X               X                X
Paternity Exclusion




        Dual
   Obligate alleles   Obligate allele




   X                              X
                               Paternity Inclusion




Obligate allele   Obligate allele   Obligate allele   Obligate allele   Obligate allele
                      Paternity Inclusion




                       Dual                                                 Dual
Obligate allele   Obligate alleles Obligate allele   Obligate allele   Obligate alleles   Obligate allele
                  Paternity Inclusion




Obligate allele      Obligate alleleObligate allele   Obligate allele
If the Alleged Father Cannot be Excluded

Several Statistical Values are Calculated to
Assess the Strength of the Genetic Evidence

      PI         Paternity Index

      CPI        Combined Paternity Index

      W          Probability of Paternity

      PE         Probability of Exclusion
           Paternity Index
• Summarizes the genetic information
  provided by the DNA analysis of the
  Mother, the Child, and the Alleged Father
• The Numerator is the Probability of
  observing the genetic results for the three
  individuals tested under the assumption
  that they are a true trio
• The Denominator is the probability of
  observing the same genetic results for the
  three individuals under the assumption
  that they are a false trio.
         Probability of Paternity
•   The probability of paternity is a measure of
    the strengths of one’s belief in the hypothesis
    that the tested man is the father.
•   The correct probability must be based on all
    of the evidence in the case.
•   The non-genetic evidence comes from the
    testimony of the mother, tested man, and
    other witnesses.
•   The genetic evidence comes from the DNA
    paternity test.
      Probability of Paternity
•   The prior probability of paternity is the strength of
    one’s belief that the tested man is the father based
    only on the non-genetic evidence.
•   P = Prior Probability; it is a number greater than 0
    and less than or equal to 1. In many criminal
    proceedings the Probability of Paternity is not
    admissible.
•   In criminal cases, the accused is presumed innocent
    until proven guilty. Therefore, the defense would
    argue that the Prior Probability should be 0. You
    cannot calculate a posterior Probability of Paternity
    with a Prior Probability of 0.
     Probability of Paternity

• In the United States, the civil court
    system has made the assumption that
    the prior probability is equal to 0.5.
•   The argument that is presented is that
    the tested man is either the true father
    or he is not. In the absence of any
    knowledge about which was the case, it
    is reasonable to give these two
    possibilities equal prior probabilities.
        DNA Paternity Testing
•   No test available can prove with a probability
    of paternity or maternity of 100% that a man
    or woman is the biological parent of a child.
•   Currently available DNA testing will routinely
    provide greater than a 99.9999% probability
    of paternity/maternity when the biological
    mother is tested in conjunction with the child
    and the alleged father. This is in excess of the
    99% or 99.9% requirement of most U.S. civil
    courts.
     Probability of Exclusion
• The probability of exclusion (PE) is defined as
    the probability of excluding a random
    individual from the population given the alleles
    of the child and the mother.
•   The genetic information of the tested man is
    not considered in the determination of the
    probability of exclusion
•   The probability of exclusion (PE) is equal to the
    frequency of all men in the population who do
    not contain an allele that matches the obligate
    paternal allele of the child.
PART 3
            Arthur J. Eisenberg, PhD
             Professor and Chairman
  Dept of Forensic and Investigative Genetics
Co-Director UNT Center for Human Identification
       Institute of Investigative Genetics
University of North Texas Health Science Center
              Fort Worth, Texas USA
                   817 735-0555
 Arthur.eisenberg@unthsc.edu

								
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