Plan Z

Balanced Translocations: 101

This is still bothering me, so excuse me while I declare a few moments of silent scientific concentration here at the Hippo. Now this Normal_4is what chromosomes one and four look like in a genetically normal person, provided they are made of playdough. The red ones are an exquisite squishy rendering of the first chromosomes, while the more diminutive fourth chromosomes are in blue.

And this is what Playdough Steve looks like.Balanced Can you see how he has both copies of one and both copies of four but one part of one copy of each chromosome has switched places? Excellent! THAT is a balanced translocation.

All cells in the genetically normal human body have two copies of each chromosome except sperm (I originally wrote that both the egg and the sperm have only one copy but it turns out I was wrong- how embarrassing for me BUT please for the love of god always point it out when I make an error like that.) Those cells are created by randomly grabbing one of each of a person's twenty-three pairs of chromosomes, so Normal_sperm_1this what the first and fourth chromosomes look like in a normal sperm cell.

Only one of each.

While it is possible for a person with a balanced translocation to create normal sperm cells (exhibit A: Patrick) they frequently get this instead.Unbalanced_sperm Chromosome one is all there plus an extra, partial copy of the one. The extra is bad, by the way. Also, only half of the fourth chromosome is present. All of the genes located on that half of the fourth chromosome are gone. That absence is bad too, in case you were wondering.

When this unbalanced sperm cell hooks up with a lovely normal egg and creates the first cell in a new embryo it looks like this. Unbalanced_cell_1Two and a half copies of the first chromosome and only one and a half copies of the fourth. THIS is the starter cell. THIS is the only genetic information that this embryo will have to work with from these two chromosomes. So, again, I ask, how could a mosaic situation exist?

This last miscarriage was caused by an unbalanced translocation. It was inherited  [unless you want to imagine a new and yet identical de novo (spontaneous) situation of such mind-blowingly coincidental proportions even typing it makes me laugh out loud, Ho ho ho] so we know that the sperm that created it was unbalanced. Therefore that very first cell was unbalanced as well. If that embryo carried normal cells as my IVF clinic would have me believe, well, I ask you, WHERE DID THE MISSING PIECES OF THE FOURTH CHROMOSOME MATERIALIZE FROM? The Piggly-Wiggly? That half of the fourth chromosome was GONE. It DID NOT EXIST.

The Playdough doesn't lie, people.

Do you want to know what I think? I think they transferred the wrong embryo, that's what I think.

And do you know what else? It does not matter one iota. It just... happened. But I did feel a need to explain why I do not think an inherited unbalanced translocation can display patterns of mosaicism.

I expect you will be seeing me and my playdough in Sweden for my Nobel prize quite soon.....

(Aw damn it. This looked much prettier in my browser window. I keep trying to move the little images so it is all slick and informative but I do not know how. I DO know this is boring, however, and I am sorry. But it is also good for you, like spinach, so buck it up campers. I did just get permission from Steve to write about his adoption and finding his birthmother so if you like more human interest and less genetics stick around.)   

Edited for clarification (I hope): Whoa, the human egg carries 46 chromosomes?? Really? Is that true? So much for Sweden...

Mosaicism is when an embryo has both chromosomally normal and chromosomally abnormal cells. Patrick won't let me have the playdough back so we are just going to have to squinch our eyes and try some Imagination Time to visualize this. It is sort of easy to see how this can happen with trisomies (trisomies occur when there are three copies of the same chromosome; Down's Syndrome is an example of this.) You could start with a trisomy and during cell division the extra chromosome could be shed and voila you have a normal cell replicating itself right along with the abnormal ones. Or, conversely, you start with a normal cell and during cell division an extra chromosome gets tacked in and voila you have an abnormal cell replicating itself right along with the normal ones. That makes sense, doesn't it? The reason I do not think that mosaicism is a reasonable explanation in our case is that the embryo must have started with missing genetic information that could not be replaced (See Playdough, above.)

If this last miscarriage had carried any other abnormality than the one it did I would say ah, yes, well, such is the mystery of meiosis (or maybe mitosis; if I got the egg thing wrong I am clearly not to be trusted too much with the biology, although my logic is flawless, thank you) but it carried Steve's very very specific translocation. Not just the same chromosomes but the q break at 33.1. Like I said, specific. 

It is easier for me to imagine a mis-labeled embryo than it is for me to imagine strange coincidences at the cellular level. I am simple like that. But but BUT I do not know. They do not know. Collectively we will never know, which absolutely kills the mystery reader in me, but other than that I can live with it.

Believe it or not, I think the clinic did a great job, over all. I am even impressed by the way they researched the cause of the miscarriage, down to bringing Steve's original karyotyping slide to DC via courier. And while I appreciate your righteous vehemence on my behalf, I still think it was decent of them to offer us anything at all towards another cycle. I know, I know, you guys believe they should cover the whole thing AND send me orchids every day but I am satisfied with less. I would certainly use them again if they were not so far away and if IVF had added one damn thing to my life. I still might, I suppose, who knows. IF the wrong embryo was transferred then I believe such an occurrence falls under the banner of easily understood human error. Frequently someone has to bear the burden of living with imperfect individuals in an imperfect world. When I was 17 I was a hostess in a nice DC restaurant. One night a couple came in to wait for a table and I completely forgot about them. Eventually I started seating people as they walked in the door and the guy who had been waiting for over an hour lost it and told me that I had ruined dinner for them, not just for that night but FOREVER. See, in that situation, he was the victim of my imperfection. Maybe it just was my turn with the PGD.

Personally, I like Ms Sisyphus' excellent theory that I was Caligula in a past life and I am paying for it now.