Monday, March 23, 2015

Mary Lyon (1925 - 2014)

Mary Lyon died on Christmas day last December. She was 89 years old.

She was a famous mouse geneticist who spend most of her working career at the MRC labs in Harwell, United Kingdom (near Oxford). The labs are known as an international center for mouse genetics.

Mary Lyon is famous for discovering the phenomenon of X chromosome inactivation. This is when one the the X chromosomes of female mammals is selectively inactivated so that the products of the X chromosome genes are quantitatively similar to the dosage in males where there's only one X chromosome. The phenomenon used to be referred to as Lyonization.

I never met Mary Lyon but from what people say about her, I'm sure I would have liked her. Here's an excerpt from the obituary in Nature: Mary F. Lyon (1925 - 2014).
Lyon was a central figure in twentieth-century mouse genetics. She laid the intellectual foundations and developed the genetic tools for the use of mice as model organisms in molecular medicine, cell and developmental biology and in deciphering the function of the human genome. Lyon was editor of Mouse News Letter from 1956 to 1970, a publication that had a key role in establishing a mouse-focused research community in the pre-Internet age. She also helped to develop a common language for the field by chairing the Committee on Standardised Genetic Nomenclature for Mice from 1975 to 1990. Her pivotal contribution was recognized by the naming of the Mary Lyon Centre, an international facility for mouse-genetic resources, opened at Harwell in 2004, and by the creation of the Mary Lyon Medal by the UK Genetics Society in 2014.

Because everything Mary said was so carefully thought through, she could be difficult to talk to: on the phone, it was easy to think you had been cut off. She did not suffer fools gladly, but was a great supporter of the bright young scientist, often eschewing authorship of publications to enhance the profile of junior collaborators. She was intellectually rigorous but not dictatorial. When I began my PhD with her in 1977, she gave me a handful of papers, showed me the genetic tools — mice carrying the various mutations and chromosomal rearrangements — and said, “do something on X-inactivation”. That degree of academic freedom was exhilarating, coupled as it was with the safety net of robust critique.

... Her first love was mice, although she always had a cat — a tortoiseshell, of course.
X chromosome inactivation is one of the classic examples of epigenetics, sensu stricto. It was the subject of one of my most popular posts of all time: Calico cats. Calico cats almost always have to be female but there are very rare examples of male calico cats. Can anyone figure out why?



19 comments :

  1. If a male is XXY then wouldn't it work similar to female cats? Would that be how male calico cats are made?

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    1. You comment does indeed seem to be confused, but it contains the germ of the right answer: male calico cats are the catty equivalent of Klinefelter's syndrome, i.e. they are cats that are phenotypically male (but sterile) with an XXY genotype.

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    2. Confused found himself a nice wiki...the standard answer is simply found on wikipedia

      There is an alternative, however, translocation or even fusion (of parts) of the sex chromosomes.

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    3. There could even be another solution to male calico cats: local derepression of epi-codes du to TE-insertions.

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    4. Actually, now I think about it, is it really the feline form of Klinefelter? Any evidence for that? Or has it just a theoretical solution propagated as the cause?

      Any references, prof Moran?

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    5. now I think about it

      Hey Peers, this is a most uncharacteristic but welcome change in behaviour.

      And the answers to your questions are no, no and no.

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    6. Some of us know little about biology and like to try and figure these things our on their own, Peer.

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  2. And almost all orange cats are male. And, in my opinion, the coolest cats ever.

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  3. I first heard about X chromosome inactivation from George Wald in the 1970s. The context was human colour vision. It turns out that, in humans, retinal opsins are established before X chromosome inactivation occurs. Thus, in a human female, half the opsins are being governed by the X chromosome inherited from the mother and the other half by the X chromosome inherited from the father. Not unlike the story for a calico cat (as I understand it). Even if there is a colour vision defect inherited from one X chromosome, this does not lead to functional colour blindness unless the defect also is present in the second X chromosome.

    I'm not a life scientist. I have, over the years, done some reading about X chromosome inactivation in the context of colour vision. In that reading, I encountered the work of Mary Lyon. I'm sorry to learn of her passing.

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  4. For colour visions blind subjects, like myself, calico cats are not orange, but brownisch...

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  5. Sometimes the Repy button works, but this is not one og those times. This is an answer to Peer:

    Actually, now I think about it, is it really the feline form of Klinefelter? Any evidence for that? Or has it just a theoretical solution propagated as the cause?

    Of course there is evidence. It took about 10 seconds to find this reference:

    Am J Vet Res. 1975 Sep;36(9):1275-80. An animal model for the XXY Klinefelter's syndrome in man: tortoiseshell and calico male cats. Centerwall WR, Benirschke K.

    If you learn how to use PubMed you'll have no trouble finding if there are more recent ones.

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  6. The abstract reads: An XXY-complement was included in the chromosome makeup of 16 of the 25 cats

    confirming my point that ther might be more than one answer to Morans question (although he did not know it himslef)

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    1. confirming my point that ther might be more than one answer to Morans question (although he did not know it himself)

      I've been teaching this stuff for 35 years. The calico cat was in the first edition of my textbook.

      What in the world makes you believe that I don't know ALL the possible answers to my question?

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  7. Did you read and understand the whole paper, or are you just quote-mining the abstract?

    Did you follow my suggestion to search for more recent references? I'm not going to do your work for you, but I'd be surprised if nothing has been published since 1975.

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  8. There is a mouse model for XXY, as you should know.

    But your reference showed there is more than one answer to Morans question. Ans yes I have access to all science papers, so if you have more: be my guest.

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  9. What does the existence of a mouse model tell us about male calico cats?

    Anyway, I didn't ask if you had access to all science papers; I asked if you had read and understood a particular one. I take your evasive answer as a no.

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  10. I know that only 16/25 have the XXY karyotype. That's sufficient. Of course, you know the whole paper. I comprise and keep space available for self-thinking (so I do not have to parrot main-streamers).

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    1. Hey Peer,

      I think you need to "comprise" some more and keep more space available for "self-thinking" - what other type of thinking is there, by the way ?

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  11. non-self thinking...i.e. parroting mean stream media propogated non-science .

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