Genetic Mosaics

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A genetic mosaic is a creature whose body is built of a mixture of cells of two or more different genotypes. In mammals they arise by several different mechanisms:

The Tetraparental Mouse

As the name suggests, tetraparental mice have four parents: two fathers and two mothers (not including the foster mother that gives birth to them!). This is how they are made: The photograph shows a tetraparental mouse derived from Note the intermingling of black and white patches.

(This mouse is not the same as an F1 hybrid produced by mating a white mouse with a black one. In that case, all the cells would be of the same genotype, and the coat would have been a uniform brown.)

The photograph (as well as the mouse) are courtesy of the late Dr. Thomas G. Wegmann.)

A Tetragametic Human

A report by Yu, et. al. in the May 16, 2002 issue of The New England Journal of Medicine documents the discovery of a tetragametic woman; that is a woman derived from four different gametes, not just two. She came to the doctors' attention because she needed a kidney transplant.

How were these results possible?

The most reasonable explanation is that

Although she was a mosaic for the HLA (and other) genes on chromosome 6, all her cells were XX. So both the father's successful sperm cells had carried his X chromosome.

However, tetraparental humans have been found that were mosaic for sex chromosomes as well; that is, some of their cells were XX; the other XY. In some cases this mosaic pattern results in a hermaphrodite — a person with a mixture of male and female sex organs.

So what are her chances for finding a suitable kidney donor?

The HLA region on chromosome 6 carries a set of genes that encode the major transplantation antigens; that is, the antigens that trigger graft rejection.
Link to a discussion.

Ordinarily, there is only a 1 in 4 chance that two siblings share the same transplantation antigens if both parents were heterozygous as in her case. [Link to explanatory diagram]

But because this woman has all four sets of transplantation antigens, she can accept a kidney from any one of her brothers as well as her mother (her father was dead) without fear of rejecting it.

Laboratory tests confirmed that she was unable to generate T cells able to react against the cells of either brother or her mother.

Rat-Mouse Chimeras

In the 3 September 2010 issue of Cell, Kobayashi et al. report the creation of healthy rat-mouse chimeras: Their procedure:

The Pdx-1−/− Mouse

Pdx-1 encodes a transcription factor that is essential for the development of the pancreas. Transgenic mice lacking a functioning Pdx-1 gene (Pdx-1−/−) die shortly after birth.

However, Kobayashi et al. found that injecting rat induced pluripotent stem cells (iPSCs) into mouse Pdx-1−/− blastocysts produced a few viable mouse chimeras complete with a pancreas made up almost exclusively of rat cells. The pancreas was fully functional producing both exocrine secretions (e.g., pancreatic amylase) and endocrine secretions (e.g., insulin, glucagon, and somatostatin).

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13 March 2012