Distinguishing genetically between the germlines of male monozygotic twins

There are intriguing differences in the rate of human twinning worldwide — with less than eight per 1000 live births in Asia to greater than 18 per 1000 live births in Central Africa. Such geographic variations are mainly due to differences in dizygotic (DZ; lay term is ‘fraternal twins’) twinning and probably is associated with social, environmental and (principally) genetic factors. On the other hand, the incidence of monozygotic (MZ; lay term is ‘identical twins’) twinning is rather constant at ~4 per 1000 live births worldwide.

MZ twins arise from a single zygote (fertilized germ cell representing fusion of one sperm and one egg), and, therefore, initially, the two split cells initially contain the same genome (hence, the layman’s term ‘identical’ twins). With every 1 in 250 males being a MZ twin, instances in which the presence of a genetic “clone” can hamper forensic casework are more than a theoretical possibility (e.g. in real-life examples, a 1999 case involved a Michigan female student who was raped; 5 years later, DNA analysis led to identification of an alleged rapist who happened to have a MZ twin brother, and both the person-of-interest and his brother denied their involvement. In 2009, Malaysian police in Kuala Lumpur arrested MZ twin brothers; when the case came to court, however, there was reasonable doubt as to which twin was involved, and both men walked free). The ostensible indistinguishability of MZ twins has also challenged the probative value of genetic testing in the context of paternity disputes. For example, in 2007, a woman in the US gave birth to a child after she had had sex with MZ twin brothers; a DNA test identified both likely fathers with 99.9% probability but, owing to the nature of the genetic markers included, could not discriminate between the two men (in the end, one brother was ruled the biological father on the grounds of other circumstantial evidence).

Coalescence of all cellular lineages in a single fertilization event is the basis of the generally held view that MZ twins are genetically indistinguishable. However, after the twinning event (i.e. after division of the original embryo), cell divisions along the lineages of one twin can be assumed to occur independently of the cell divisions in the other twin — at least regarding acquisition of de novo mutations (i.e. somatic mutations vs germline mutations) Therefore, given the number of cell divisions during embryonic development, and size of the human genome, there is a reasonable chance that any two tissue samples taken from MZ twins after birth may differ, due to the presence or absence of one or more post-twinning genetic alterations.

One way to overcome this problem of detecting post-twinning somatic mutations — is to use whole-genome sequencing (WGS)

technology, which represents a genome-wide search for those few mutations that occur during early embryonic development and hence allow one to distinguish between MZ twins in later life. Following this approach, the first cases of criminal sexual offense have been solved successfully by Eurofins Genomics and Forensics Campus — leading to identification of sperm sample donors from saliva reference samples taken from MZ twin suspects.

As a matter of principle, however, the residual uncertainty of the experimental results needs to be evaluated and reported as well. Authors [see attached article] therefore developed a novel mathematical framework to quantify the evidential power of genetic data — in alleged rape cases endeavoring to distinguish between MZ twin donors, based upon comprehensive DNA sequencing. Moreover, authors demonstrate that the same mathematical method can be used to resolve paternity disputes involving alleged fathers who are one of two MZ twin brothers.

[P.S. I might add that many epigenetic variations (i.e. alterations not involving DNA sequence changes) have been reported — which can distinguish one MZ twin from the other.]


PLoS Genet Dec 2o18; 14: e1007756

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