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378    Chapter 11    Analyzing Genomic Variation


              CODIS database. All 50 states mandate the collection of   conclusive evidence in paternity suits, and DNA finger-
              DNA fingerprint data for CODIS from felons convicted of   prints can be used to identify human remains, as was the
              certain crimes, such as sexual offenders; the database also   case for the victims of the World Trade Center disaster
              includes profiles from missing persons.              on September 11, 2001. The benefits of this technology
                  As of 2016, CODIS has assisted more than 300,000   are not restricted to DNA fingerprints of humans. Wildlife
              criminal investigations. Typically, forensic investigators   biologists study populations of endangered species by
              use the database to match the DNA profile of evidence   fingerprinting individual animals to increase the chance
              left at crime scenes with that of a felon. But DNA can   for success of captive breeding programs or to identify
              also establish innocence: Suspects can be excluded if no   illegally poached animals. Owners of valuable domesti-
              match with crime scene evidence exists. In fact, a public   cated animals such as show dogs, thoroughbred horses,
              policy organization called the Innocence Project has used   or cattle can in some cases establish lineage through
              DNA fingerprint evidence to help exonerate more than   DNA fingerprints. In one fascinating if bizarre case from
              300 people convicted of capital crimes, including several   Argentina, scientists were enlisted to help apprehend a
              who were awaiting execution.                         butcher who moonlighted as a cattle rustler. Meat hang-
                  The  power  of  DNA  fingerprinting  technology  raises   ing in the butcher’s shop had the same DNA profile as a
              many concerns about privacy and possible discrimination in   tissue sample that a rancher had taken from one of his
              the collection of data. Just to give one interesting example,   cows before it was stolen.
              consider that siblings will share 50% of all SSR alleles; the
              same is true of parents and children. As a result, it is possi-
              ble to identify the perpetrator of a crime not by a match to   DNA Microarrays Genotype
              his or her own DNA, but instead by a partial match to the   Millions of SNPs
              DNA of a close relative. This kind of familial DNA search
              was critical for the apprehension in 2010 of the major sus-  Nucleic acid hybridization, the ability of complemen-
              pect for the “Grim Sleeper” serial killer in Los Angeles. The   tary single strands of DNA or RNA to come together to
              suspect’s son had recently been convicted on a felony weap-  form double-stranded molecules, is the basis for many
              ons charge, so his DNA was analyzed. The son’s DNA pro-  techniques in molecular biology. We have already dis-
              file partially matched DNA fingerprints from semen and   cussed the importance of hybridizing oligonucleotide
              saliva found on the Grim Sleeper’s victims. Policemen fol-  primers to DNA templates in Sanger DNA sequencing
              lowed the father, and one detective posing as a waiter ob-  and in PCR. Both DNA sequencing and PCR assume that
              tained a partially eaten slice of pizza with the father’s DNA.   a perfect complementary match exists between all the
              Stunningly, this DNA was a perfect match with the crime   nucleotides in the primers and templates. But what will
              scene evidence. (The trial has just begun as of this writing   happen if a mismatch exists between two single strands
              in early 2016.) Should criminal investigators be allowed to   of nucleic acid?
              conduct such familial searches given that family members   Consider a 21-base oligonucleotide that hybridizes to a
              of felons who have not committed any crime are in effect   target strand that differs at a single base in the middle of the
              under lifelong genetic surveillance?                 sequence (Fig. 11.16). The resulting double-stranded
                  DNA fingerprints have many important uses beyond     hybrid is significantly less stable than a similar hybrid in
              forensics for capital crimes. They now provide the most   which all the nucleotides match. The reason is that the




              Figure 11.16  Short hybridization probes can distinguish single-base mismatches. Researchers allow hybridization between a
              short 21-base probe and two different target sequences. (a) A perfect match between probe and target extends across all 21 bases. When
              the temperature rises, this hybrid has enough hydrogen bonds to remain intact. (b) With a single-base mismatch in the middle of the probe,
              the effective length of the probe-target hybrid is only 10 bases. When the temperature rises, this hybrid falls apart.
                               (a)  21-base probe/target hybrid with no mismatches
                                            Probe            Raise
                                                             temperature
                                    Completely complementary
                                          target strand
                               (b)  21-base probe/target hybrid with middle mismatch
                                                             Raise
                                                             temperature

                                             Mismatch at base 11
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