Re: Is there any physical evidence of a 'Chimera twin' other than DNA?

Chimera twins are very rare, resulting from the fusion of two separate embryos early in 
development. There are a number of examples of clinical cases of somatic mosaicism that were 
apparent from techniques other than DNA analysis.

The OMIM entry for the XG blood group describes a chimera twin apparent because red blood 
cells had different ABO types:
 http://www.ncbi.nlm.nih.gov:80/entrez/dispomim.cgi?id=314700

The citation is:

Ducos, J.; Morty, Y.; Sanger, R.; Race, R. R. :
Xg and X chromosome inactivation. Lancet II: 219-220, 1971. 
PubMed ID : 4104885

There is also a report of a possible chimera twin in which one genotype was affected by 
Duchenne muscular dystrophy:
 http://www.ncbi.nlm.nih.gov:80/entrez/dispomim.cgi?id=310200

There is a dramatic first-person account of the difficulty of being a chimera twin in which the two 
genotypes were male and female. Because the fusion of twins occurred relatively late in 
development, after sexual differentiation had begun, the affected individual was born with an 
intersexual phenotype:
 http://www.medhelp.org/www/ais/stories/jane2.htm

In general, a chimera twin could be suspected if the two genotypes differ with respect to some 
trait that is evident through medical tests or observation. This trait must be cell autonomous, 
meaning that the phenotype of an individual cell is wholly determined by its genotype and is not 
influenced by other genotypes present in that individual. Ordinarily, we would not expect 
chimera twins made up of cells of the opposite sex to be intersexual, because sexual 
differentiation is driven by the production (or lack of production) of androgens by cells in the 
presumptive gonad. Half of all chimera twins are made up of genotypes of the opposite sex, so 
these would be very easy to spot if sex determination were cell autonomous.

As another example, consider a chimera twin in which one genotype is albino. This individual 
would be suspected of somatic mosaicism because of their appearance. There are other 
mechanisms of somatic mosaicism besides chimera twins.

To take a very common example, all females are somatic mosaics for X-linked traits because of 
X-inactivation. In the case of women heterozygous for color blindness, they have mosaic retinas 
with some cells that are color blind, which can be detected by very sensitive tests for color vision. 
In some individuals, there will be a large clone of color-blind cells in the center of the visual field 
and these individuals will be effectively color blind in one eye.

To fully answer your question, I am sure that there are undetected cases of chimera twins. If the 
two genotypes are not different with respect to some obvious phenotypic difference that is cell 
autonomous, somatic mosaicism will not be apparent, although it might be discovered 
accidentally during medical tests of some kind.

Yours,

Paul Szauter
Mouse Genome Informatics