From: Rafal Smigrodzki (rms2g@virginia.edu)
Date: Thu Sep 12 2002 - 09:50:02 MDT
Wei Dai asked:
>
> How does reproduction work naturally? Do our bodies manage to keep our
> germ cells from being damaged, or is there an internal sieve to
> filter out the damaged germ cells? Can we make use of these natural
> mechanisms for reproductive cloning?
### The sieve is during is during oogenesis, with 99% of oocytes dying after
being challenged to develop into ova. I don't know if there is a similar
sieve in spermatogenesis but I wouldn't be surprised if there was. At least
in case of ova it is a sieve and not preventative protection from damage.
Additionally, there is about 90% attrition of embryos during (especially
early) pregnancy. This works also in cloning, explaining the low success
rate of this procedure. If the natural process works only in one in ten,
then the 1/100 success rate of cloning is not that bad.
Presumably, we could develop an assay for gene expression patterns in the
preimplantation embryo (e.g. do RT-PCR with universal primers on a single
cell from the embryo, and then a microarray test for the right mRNA's), and
apply some additional selection to weed out the abnormal ones before
pregnancy begins. With total genome sequencing of the nuclear donor cells
(you take a small sample of the cells right before nuclear transfer) we
could even weed out genetic defects before cloning begins. Such a procedure,
which might become possible in the next ten years if the Perlegen project
works out, would be safer than natural procreation.
Rafal
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