April 4, 2009

Identical twins and Forensic Genetics

The main interest of Forensic scientist is to establish minimal differences between two individuals. The unique situation in which we cannot conclude this is in the case of identical twins or monozygotic twins. There are two types of twins: fraternal and identical. Fraternal, or dizygotic, twins are different in their genetic make-up whereas identical, or monozygotic, twins are genetically the same. Monozygotic twins develop from the same ovum, are always the same sex and share identical genetic information. They also tend to be alike in both physical and mental characteristics. Furthermore, in the last years a few cases published in the media have shown this conflict on the DNA application in the Court. With identical twins, even if you sequenced their whole genome you would not find differences, they are practically clones. There is simply no test that explains the difference between two identical twins, at least for now.

The cases are:

Case 1: Two years ago, identical twin brothers Raymon and Richard Miller both had sex with the same woman who became pregnant. In May 2007, the judge decided that Raymon is the legal father of the child although the DNA paternity test couldn’t provide definitive proof, and the child support was split between the two brothers.
Who's Your Daddy? Paternity Battle Between BrothersJudge Uses Old-Fashioned Detective Work to Determine Who the Father Is... When the paternity test came back with the same results, he took the matter to the courts where Judge ruled that even in light of the identical DNA tests and overlapping relationships, Raymon would remain the legal father of the child. Raymon hopes to continue appealing the decision. In Missouri, a paternity test must come back with 98 percent or higher probability that DNA matches in order for a man to be named the legal father.
Case 2: In February, millions of dollars worth of jewelry was stolen in Berlin. Two of the suspects are identical (monozygotic) twins, Hassan and Abbas O. DNA analysis showed that one or both of them were probably at the scene of the crime but it’s impossible to tell. If only one of the brothers is guilty, investigators can’t tell for sure which one it is.
Berlin's Massive Jewelry Heist
Perfect Genes for a Robbery - Investigations into the spectacular heist at Berlin's luxury department store KaDeWe have run into a problem: The suspected robbers may be identical twins. That means that the traces of DNA found at the crime scene could be useless under German law. Investigators identified the brothers using clearly identifiable traces of DNA from a glove found at the scene of the crime, according to police… Then there's the fact that the DNA, which ordinarily would serve as powerful evidence, may prove worthless in obtaining convictions for the KaDeWe case. It is impossible to distinguish between the DNA of identical twins using the kind of genetic analysis typically used in law enforcement,... German law limits the amount of genetic analysis that can be carried out by investigators.
Case 3: In Malaysia, investigators were unable to figure out which one of a pair of identical twins trafficked 166 kilograms of cannabis and 1.7 kilograms of opium. A judge dismissed the case and both twins were set free.
Identical twin escapes hanging in Malaysia after judge fails to tell brothers apart. An identical twin has escaped execution in Malaysia after a judge ruled it was impossible to determine which brother was the drug trafficker. The twins wept and embraced after judge dismissed the case. According to the judge there was no doubt that either Sathis Raj or Sabarish Raj, both 27 years old, was guilty of trafficking 166 kilograms of cannabis and 1.7 kilograms of opium, but because they looked the same and had the same DNA it was impossible to determine which one.
In reality, identical twins do not have perfectly identical DNA due to epigenomic chemical modifications and DNA copy number variations.


Epigenomic chemical modifications
Human monozygotic (MZ) twins occur in about 1 in 250 live births. Since they are derived from a single zygote, they are considered genetically identical. However, discordance is well known for many phenotypic traits and diseases. This discordance is typically attributed to differences in placenta, amniotic sac and vascularization of separate cell masses or even mosaicism in their genetic and cytogenetic composition. Epigenetic factors that influence expression of genes represent another potential difference that could explain phenotypic discordance between MZ twins. There are 2 major classes of epigenetic alterations of genes: methylations of cytosine at cytosine-guanine (CpG) dinucleotides and acetylations and methylations of DNA bound histones. Cytosine methylation at regions of gene promoters rich in CpG dinulceotides usually silences genes, whereas histone acetylation is frequently associated with activation of genes.
The largest twin study on epigenetic profiles yet reveals the extent to which lifestyle and age can impact gene expression, an international research team reports in PNAS journal. Senior author Manel Esteller of the Spanish National Cancer Center in Madrid and colleagues found that 35% of twin pairs had significant differences in DNA methylation and histone modification profiles. DNA methylation can be caused by environmental exposures, such as diet and physical activity.
Methylation can lead to differences in gene expression and as we age, the amount of DNA methylation increases.
DNA copy-number-variation profilesAnother way in which the genomes of identical twins may differ is in copy number variation (CNV) that appears as segments of DNA that are missing, occur in multiple copies, or have flipped orientation in the genome. Identical (monozygotic) twins have been found to have different CNVs which could explain why even identical twins are not truly identical in appearance or other physical characteristics despite similar environmental exposures. For example, one twin sometimes develops a disease while the other does not.