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Rare new kind of twins: boy and girl are semi-identical (cbc.ca)
125 points by pseudolus 21 days ago | hide | past | web | favorite | 61 comments



> Because of the odd combination of DNA picked up from the two sperm, doctors have been concerned that the twins might be vulnerable to cancer of the reproductive organs.

Why does 'different DNA' automatically assume cancer?


That's just the article's handwaving. The case report actually says:

> During follow-up at 3 years of age, routine ovarian surveillance showed Twin 2 to have gonadal dysgenesis, and prophylactic oophorectomy was performed.


Yea, this is highly clarifying. The OP article makes it sound like they decided to render Twin 2 sterile because of a risk of cancer inferred from some theorizing about the genetics of a these new sorts of twins. In fact, it sounds like Twin 2 was already sterile.

> Streak gonads are the defective development of the gonads in an embryo, with reproductive tissue replaced with functionless, fibrous tissue, termed streak gonads. [It is] a form of aplasia, resulting in hormonal failure that manifests as sexual infantism and infertility, with no initiation of puberty and secondary sex characteristics.


" Having both male and female pairs of sex chromosomes throughout various cells in the body is linked to certain developmental problems in the reproductive organs as well as cancer, Gabbett said"


I guess it might also be possible, then, for semi-identical twins to have different fathers?


Probably many a trillion times less likely. Already, in the history of genetic testing we’ve noticed two among billions, even with retrospective testing of ancient DNA.

While we haven’t tested all living humans, we certainly know the typical rate of fraternal twins, so, with that as a benchmark for how infrequent twins usually are, over millions of years, this happens even less. Even with lawlessness, relaxed social norms and the simultaneous sharing of sexual partners throughout history. Even with evolutionary ancestors like higher primates.


But it could be done in vitro maybe.


this happens all the time in other animals. i'd adopted two cats (boy and girl) who were littermates but had different fathers. their coat patterning and eye color were different even though their coloring and (small) size were similar.


Animals that commonly produce liters of multiple offspring typically do so by releasing multiple eggs simultaneously in each period of fertility. This also happens in humans in the case of fraternal twins (two eggs each fertilized by a different sperm).

That’s very different from one egg being fertilized by a single sperm and then splitting (which produces identical twins) or being fertilized by two sperm (which is what happened in this case).


right, that was a bad example (multiple eggs with multiple sperm from different fathers, not single egg with multiple sperm). i can't remember where, but i do remember reading about this happening in other animals.


That's fraternal twins, though, not identical.


My question here is: why is this so rare? Given how many spermatozoids are involved in every sexual contact, why doesn't it happen much more often for two of them to fertilize one egg?


Race conditions are the toughest to debug. They only show up sporadically.


https://en.wikipedia.org/wiki/Polyspermy has some short but interesting discussion of the theoretical background.

A polyploid zygote is completely nonviable, a pure waste of the egg, sperm, and other mating effort that went into it. It's in the interest of the mother and the father for the egg to be fertilized by exactly one sperm.

But it's in the interest of an individual sperm to be the one that fertilizes the egg instead of dying uselessly. So they get faster, more efficient, and more penetrant over time. When they're too effective, multiple sperm may get into an egg before the defenses are up. (Which, again, just kills the sperm that "won" the race, so you don't expect to see incredibly rapid progress in this area.)

Oceangoing eggs respond by having a fertilized egg's defenses go up really quickly, because the egg is floating around in the ocean and it's hard for the mother to influence that environment.

Female mammals have responded with slower defenses, but internal characteristics that tend to retard or hurt sperm as they make their way towards the egg, meaning that it's rare for multiple sperm to all get there at once. This is good for avoiding polyploidy, but bad for fertility -- it is not necessarily the case that even one sperm will make it.

It's interesting to see competition among sperm hurting the reproductive chances of the male and female producing and accepting it.


<3


My understanding (I'm a doctor but NOT an expert in this area) is that it usually is a long, difficult journey to the egg, and the chance of many getting there at exactly the same time is low. When a spermatozoan buries into the egg a reaction is caused which prevents other sperm from being able to penetrate.

An expert may be able to clarify, but I think this is the gist of it.


It's called the cortical reaction:

https://en.wikipedia.org/wiki/Cortical_reaction


> When a spermatozoan buries into the egg a reaction is caused which prevents other sperm from being able to penetrate.

This is an explanation I was looking for. Thanks.


I thought that was general knowledge. It certainly was part of the sexual education I got at school.


Sometimes, after many years, some people forget some of the irrelevant details of their education.

Do you remember all the steps in the ATP cycle?


"Not so irrelevant now is it"

Your teacher, maybe.


same here.. unfortunately we can't assume reproduction was a fairly covered topic at schools across the US however.


Given that this appears likely to cause the death of one or both twins (on the assumption, not true here, that there's no such thing as prophylactic surgery to remove precancerous gonads), it doesn't seem like the rarity really requires an explanation. Contra what the article says, these twins are not in good health.

If you're asking "what is the mechanism that makes sure this doesn't happen?", as opposed to "why doesn't this happen more?", that's a better question and I don't know the answer.


It's because once the egg is fertilized it gets deactivated and can't be fertilized again

For 2 or more to fertilize at same time, they've to arrive at roughly same time before the deactivation completes

So this becomes rare because the window of deactivation is quite short and not many make their way to egg.


Just goes to show how amazingly diverse and complicated sex differentiation is


I’ll probably be downvoted to the ground for being so politically incorrect, but... no.

This isn’t a “celebration of diversity” kind-of-thing. It’s an oh-fuck-look-how-this-broke kind of tragedy (particularly if you read the references posted in the commentary that indicate an amputation).

Celebrating diversity has a place. This is not it. Genetic machinery glitched majorly and these two children will have a difficult time ahead of them. Yes, we’ll get interesting one-off scientific observations, but that’s hardly a total reward.


You're reading into that comment a lot more than is warranted I think.

This does show how diverse and complicated sex differentiation is. The comment does not claim this is a virtue, or that the outcome in the article here is to be celebrated.

"Diverse" in this context I took to mean "varied", not in the sense of social diversity.


They’re not ‘varied’: one’s genotype and phenotype is female, and the other’s genotype and phenotype is male.

EDIT: Apologies, the poster below showed I am incorrect.


"The girl and boy each have male and female sex chromosomes — in other words, each twin has some cells that carry an XX pair (female) and some that carry an XY pair (male)."

They are both genetically ambiguous and present differently due to hormone generation rates.


You’re right, I’m wrong.


Interesting. This would imply that they're both genetic chimeras, as they don't carry a uniform genotype throughout their cells.


The female's sex is varied in the sense it differs from the standard female (gonadal dysgenesis).

Around 1 in 100 humans don't fit the standard male and female definitions according to http://www.isna.org/faq/frequency


Yeah I meant diverse without any kind of value judgement


Not really sure how it shows that at. Sexual differentiation is not exactly diverse at all. Genetics are complicated I'd give you that and pretty amazing that it works as it does. Though there can be complications as in this case.


The fact that humans can be XO; XXY; be XY but Androgen insensitive, and so present as female; have mosaic X/XY; or be XX/XY chimeras like the twins in this article shows that sexual differentiation can absolutely be diverse.


Wait a minute:

> The twin boy and girl were found to have 100 per cent of their mother's DNA in common, but were only 78 per cent identical in the paternal DNA they carry.

78% identical seems like a lot more than the expected 50%. How likely is it for two sperm to be 78% identical?

Also:

> Because of the odd combination of DNA picked up from the two sperm, doctors have been concerned that the twins might be vulnerable to cancer of the reproductive organs.

> "It turned out that the girl just had some changes in her ovary that people weren't comfortable with, so unfortunately she had to have her ovaries out," Gabbett said. "The boy is continuing to have his testes monitored" with ultrasound.

> "Otherwise," Gabbett said, "the two twins are beautiful kids, well and healthy."

So gee, other than the fact that they're (probably) both sterile, they're well and healthy. How reassuring.


Bearer of bad news[0], here:

>While the children were delivered by caesarean section and appeared healthy, it was found the baby girl had developed a blood clot shortly before birth. Her arm was amputated when she was four weeks old.

Odd that TFA mentions the blood clot but not the amputation, and then claims the twins are in good health besides the ovary issues.

[0] https://www.theguardian.com/science/2019/feb/27/scientists-s...


> How likely is it for two sperm to be [at least] 78% identical?

According to the paper:

> "Our results show that the twins share 78% of their paternal genome, which is 1.5 SD above the expected 50% allele sharing of independent paternal genomes."

1.5 SD and above corresponds to a 6.7% chance likelihood, or 1 in 15.


They mentioned a 3rd embryo not being viable as it only contained sperm DNA. How the DNA was divided up was probably fairly arbitrary.


Ahh, I see. They're 78% identical in paternal DNA because the same set of paternal DNA got into both embryos, not because two sperm were exceptionally similar.

This is underplayed by the terminology "semi-identical twins, with the same maternal DNA but different paternal DNA". They are significantly more identical than that. I bet twins actually matching that description wouldn't have the developmental problems these have apparently already manifested.

I wonder if the boy might have any symptoms of Klinefelter syndrome? (On the assumption that the two sperm were an X and a Y.)


> They mentioned a 3rd embryo not being viable as it only contained sperm DNA.

The CBC journalist misunderstood what the research article was saying. They did not detect Y1-Y2 cells, but cite research on bovines zygotes that found that in addition to the X-Y1 and X-Y2 cell lines, a Y1-Y2 cell line will also form, but this cell line will "undergo growth arrest before somitogenesis", accounting for why they did not find such cells in these twins. So the zygote can be presumed to have had cell lines with three different detectable gene combinations, but the paternal-paternal line cells are entirely or at least mostly terminated very early in development. Figure 3 in the original paper is a really nice illustration of how this proceeded. There was never a separate paternal-paternal embryo, contrary to the journalist's misunderstanding, but there likely was a separate paternal-paternal cell line. It's conceivable there could still be trace Y1-Y2 cells in both twins (just as both have X-Y1 and X-Y2 cells), but they are below limits that were detectable in the study and most likely they all were arrested from further division and died off.


> So gee, other than the fact that they're (probably) both sterile, they're well and healthy. How reassuring.

I'm sure it is reassuring for their parents and loved ones. Why the sarcasm?


> So gee, other than the fact that they're (probably) both sterile, they're well and healthy. How reassuring.

Does having a vasectomy make you not "well and healthy"?

I'm infertile myself, and have managed a reasonably decent quality of life despite that. Even had kids (via donation).


Many amputees also have long and fulfilling lives, but it would be misleading to describe a patient as "well and healthy" when they required an amputation as a result of the medical condition under discussion.


As it happens the girl needed her arm amputated as well because of a blood clot.


> 78% identical seems like a lot more than the expected 50%. How likely is it for two sperm to be 78% identical?

Statistics doesn't work that way. Each chromosome has a 50% chance of being shared between both children. It's possible, but unlikely, that each child would have all the same chromosomes from the father; or share none of the chromosomes from the father.

Random events have no memory. Meaning, if you flip a coin and get heads, the coin has no memory that makes it more likely to get tails on the second flip.

Thus, while each chromosome has a 50% chance of being shared, there is no "memory" that ensures that both children share half of their father's chromosomes.


> Statistics doesn't work that way.

I asked how likely it was for two sets of gamete chromosomes to be similar at levels a particular distance from the expected mean similarity. That's pretty much exactly the kind of question statistics handles.

> Each chromosome has a 50% chance of being shared between both children.

On the other hand, biology really doesn't work this way. Chromosomes recombine in meiosis; you shouldn't see a child sharing any entire chromosome, except the father's sex chromosome, with either parent.


Typically there are only 3-4 crossovers per chromosome. This means that large chunks of DNA get copied together, and as such the assortment of every base is not as simple as assuming each has an independent chance of ending up in a gamete. Rather, nearby bases are extremely likely to go into the same gamete.

This is why it's quite possible to get gametes that are similar in quantities much higher than the "expected" 50%. Instead of being 3 billion items randomly assorted, it's roughly 22 chromosomes x 4-5 chunks = 100 of so chunks of DNA, albeit split at random locations.

This simply spreads out the "normal" distribution. 50% is still the expected similarity of any two gametes, but it's not surprising for any two to be much more similar, or much less similar.


While technically accurate that headline sure doesn’t anchor feelings in the right spot. It feels inappropriate to highlight people’s tragedy as a novel scientific observation, even if true.


Why is this a tragedy? They have 2 beautiful, healthy children.


The girl has had her arm amputated and her ovaries removed, and she’s 4. “Healthy” is not the word I would use.


She was unhealthy before her arm and ovaries were removed. Now she is healthy, if partially disabled. We are fortunate to live in a time where arms and ovaries can be largely compensated for. By the time she is of child-bearing age, if she chooses, she might well have the option to undergo a semi-cloning procedure as part of in-vitro fertilization to create an embryo that contains a blend of her and her mate's chromosomes akin(ha!) to if she had functioning ovaries.


I believe that was in reference to the "first" discovered semi-identical twins, unless I misread the article.

But, it's rather unfortunate in either case.


I missed that. How terrible.

Still, having children is a miracle, not a tragedy, though tragedies may be involved.


"In addition, the girl and boy each have male and female sex chromosomes — in other words, each twin has some cells that carry an XX pair (female) and some that carry an XY pair (male). Having both male and female pairs of sex chromosomes throughout various cells in the body is linked to certain developmental problems in the reproductive organs as well as cancer, Gabbett said. When the doctors examined the girl twin's ovaries, they found some changes linked to cancer, and so "the difficult decision was made to remove them so she didn't develop cancer," he said.

The girl also developed a blood clot shortly after she was born — blood clots are a common complication for identical twins in general — and the clot cut off the blood supply to her arm. As a result, doctors also had to amputate her arm."

"When, in a separate unlikely event, the blastocyst divided into two – creating twins – more of the cells with genetic material from one sperm (which had an X chromosome) ended up in one embryo, while the other had a greater proportion of cells formed by the other, Y chromosome bearing sperm. This is why one fetus developed female characteristics and the other male, although both twins have cells from both sperm in their bodies, making them chimaeras"


> When, in a separate unlikely event, the blastocyst divided into two – creating twins – more of the cells with genetic material from one sperm (which had an X chromosome) ended up in one embryo, while the other had a greater proportion of cells formed by the other, Y chromosome bearing sperm. This is why one fetus developed female characteristics and the other male

Rather than the male embryo having more Y-chromosome bearing cells overall, I think it's more likely that the male embryo developed that way because the cells that became the gonads -- as opposed to the majority of all cells -- had Ys. Sexual development isn't done by majority vote.


Oh, interesting. That was totally missing from the original article. I had assume that the twinning was because the egg had been fertilized by two sperm cells.

Rather, it seems that it's quite possible for any single-birth pregnancy to involve two sperm cells, and would result in a chimera. The fact that this one split into twins was a separate event.


The really simple model for an egg being fertilized by two sperm is that you'd get one fertilized zygote with three sets of chromosomes, fully triploid. Such a zygote would miscarry pretty quickly.

To get a less nonviable chimera, you need the egg to divide exactly once, such that one half gets one of the sperm and the other half gets the other one. If there is a mechanism that tends to ensure this happens, then it feels like that mechanism might also be related to the twinning (tripling, apparently) of the zygote under discussion here.


Happens all the time with cats!


Not the same thing. 2 eggs, 2 sperms. Here it's one egg, two sperms.


Ahh. Yes, you are right.




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