Wednesday, October 19, 2005

How do you like your eggs in the morning?

The answer is "damaged" according to this story.
Many eggs used for IVF carry genetic errors that can cause miscarriage, even those from young women, experts say.

The risk of miscarriage and chromosomal abnormalities or aneuploidy increases as a woman ages.

Until now, many had thought eggs from younger women were more likely to be defect-free.

However, the three new studies suggest that on average 42% of eggs from all women have serious genetic defects that could prevent embryos surviving to term.

Dr Jeffrey Nelson of the Huntingdon Reproductive Center in California used PGD to screen 289 embryos from 22 healthy egg donors, all of whom were under 30.

Overall, 42% of the embryos had aneuploidy or abnormal chromosomes.

To those of us who actually know something about genetics, this will not come as a massive surprise. There are several reasons why this high level of defects should occur.
  • Firstly, DNA replication is not as reliable as everyone thinks: errors occur quite frequently. Often these are not in important places, but in the so-called "junk genes", i.e. genes that do not appear to actually do anything in humans.

  • Secondly, DNA has a shelf-life. Since a woman in born with all of her eggs—whereas sperm are constantly manufactured in the testes—there is deterioration over her life-time. There is a reason why the menopause exists. It is also why—from the point of view of having a higher chance of a healthy child—it is advisable for women to have a child as young as possible.

  • There are very often defects in the single strand of DNA in sperm and eggs (since there is no "opposite key" strand deployed to check errors). This is why we reproduce sexually; the hope is that, although a gene may be damaged in, for instance, the egg, this defect will be masked by a healthy counterpart in the sperm. Usually, though not always, defective genes are recessive, and will be successfully masked by the working gene.

This last is the reason that genetic abnormality is relatively rarely expressed in humans. There are, of course, relatively standard exceptions, e.g. sickle cell disease.

Sickle cell is an interesting example of genetic deformity. If we imagine that A is the normal gene, and B is the gene for sickle cell, we can illustrate the combinant effect.
  • A + A = normal red blood cells

  • A + B = slight cell deformity only in low-oxygen conditions (heterozygous form)

  • B + B = red blood cells are severely sickle shaped, tending to cause capillary blockage, internal haemorrhaging, organ and bone damage. Sickle-cell anaemia (homozygous form).

Sickle-cell tends to occur more often in Africans, and this is for a very good "selective pressure" reason: sickle-cell confers a strong resistance to malaria. The homozygous form, whilst conferring a near-immunity to malaria, does tend to severely shorten the lifespan of the sufferer, and causes acute pain. Treatment, which typically includes blood transfusions, is also wearing, both physically and financially. The heterozygous form, on the other hand, is obviously the best form to have since it confers this resistance and has very few side-effects (unless you are climbing a mountain).

Unfortunately, the heterozygous person is a carrier and, as the number of carriers increases (as it will as malaria continues to increase) we will see more and more homozygous victims (if two carriers mate, there is a 1 in 4 chance of no B gene, 2 in 4 of one B (heterozygous) gene and 1 in 4 of homozygous B). We will then see an interesting battle between which is the more likely to confer a selective advantage: a resistance to malaria and short lifespan, or no sickle-cell and no resistance to malaria. Even more interesting, of course, is that our medical technology is the thing most likely to be a telling factor.

I just throw that in for you to mull over...

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