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Autosomal trisomy syndromes are usually lethal but sex chromosome number related abnormalities do not lead to that much fatality. why?

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  • $\begingroup$ To support mdperry's answer: ncbi.nlm.nih.gov/pmc/articles/PMC2429870 Figure 2 in particular should draw your attention as it shows the previously mentioned correlation between chromosome size, transcripts and embryonic viability. Apologies, I would have added this in comment form but I do not have enough reputation. $\endgroup$ – user15037 Mar 21 '15 at 16:27
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It has to do with dosage compensation:

  • The Y chromosome contains relatively few genes. Interestingly, chromosome 21 and 18, which are over represented in the most common viable trisomies, are also relatively small.
  • Humans already possess a mechanism to compensate for additional X chromosomes: X-inactivation. Normally this inactivates one of the two X chromosomes in females but can also inactivate two in cases of X trisomy.

Humans are much more able to tolerate extra sex chromosomes than extra autosomes. … Compared to autosomal trisomies, … sex chromosome trisomies are fairly benign. Affected individuals generally show reduced sexual development and fertility, but they often have normal life spans, and many of their symptoms can be treated by hormone supplementation. The ability of humans to tolerate supernumerary sex chromosomes is quite remarkable, as individuals can survive with as many as four sex chromosomes. This tolerance most likely relates to both X inactivation and to the small number of genes on the Y chromosome. In fact, when cells from individuals with more than one copy of the X chromosome are analyzed under a microscope, all but one of the X chromosomes appear as condensed Barr bodies, the cytological manifestations of X-chromosome inactivation. Supernumerary copies of the Y chromosome may be tolerated because the few gene products of the Y chromosome are not required for survival.

From: Chromosomal Abnormalities: Aneuploidies by Clare O'Connor (emphasis added)


An added bonus (and I feel as though I should actually write something myself), I recently read a paper studying trisomy 21:

Jiang J, Jing Y, Cost GJ, Chiang JC, Kolpa HJ, Cotton AM, Carone DM, Carone BR, Shivak DA, Guschin DY, Pearl JR, Rebar EJ, Byron M, Gregory PD, Brown CJ, Urnov FD, Hall LL, Lawrence JB. 2013. Translating dosage compensation to trisomy 21. Nature 500(7462):296-300.

Using zinc finger nucleases, they inserted a XIST transgene into chromosome 21 of cells derived from Down syndrome patients. XIST is a gene centrally involved in X-inactivation. They found that, by inserting it into chromosome 21, they were able to silence one and revert the trisomic cells to a more normal phenotype.

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First it depends on the species in question. I assume that you are referring to humans and/or mice. In diploid organisms the toxicity of losing or gaining a chromosome is related in part to the size of the chromosome, but also determined by which genes are on the chromosome in question. Some genes could be lethal if their copy number is increased or decreased (dose sensitive). The longer the chromosome the more genes it is likely to have and therefore the greater the chance of a problem. In humans viable trisomics usually involve the shortest chromosomes. Human X is very large but it is dosage compensated.

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    $\begingroup$ This is an interesting answer. A reference or two would cheer things up. $\endgroup$ – AliceD Mar 20 '15 at 4:38
  • $\begingroup$ @AliceD: Thank you for the feedback. I am just learning to use markdown, and so thus far my answers and comments lack formatting. I am also limited to using mobile devices when composing, and have not mastered the skills required to cut and and paste images and URLs between Apps. My working hypothesis is that individuals posting questions here are familiar with search engines (and so any references I insert would be largely redundant). Therefore I limit my posts to material that might not be easily found on the Internet. I have also updated my profile to explain my knowledge base. $\endgroup$ – mdperry Mar 20 '15 at 11:18
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    $\begingroup$ Yes folks will probably be aware of how to use google, but without references answers are generally scrutinized and not upvoted, or even downvoted. Everyone can write up unfounded fancy stuff. The art of answering is to give folks the opportunity to do further reading and confirm the answer. That's how this site works. The fact that half of your answers remains not voted upon supports this notion. Don't generate your own working hypotheses. The help center is a good source of info. $\endgroup$ – AliceD Mar 20 '15 at 11:22
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The morbidity is high because autosomal trisomies affect somatic / autosomal chromosomes, which are essential to the process of life. In fact, the majority of fetuses affected by autosomal trysomy are miscarried, with a few exceptions (Down syndrome is one). The sex cells have only half the number of chromosomes,23, of which the affected ones are usually the XX or XY. Their functions are different and although tremendously important, they are not vital, people can survive and live normal lives with these disorders: X, XXX, XXY, XYY. Mader, chapter 24.

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    $\begingroup$ X chromosome contains many vital genes. $\endgroup$ – WYSIWYG Jun 21 '15 at 5:35
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Assuming you are discussing our species, sex chromossomes abnormalities do not lead to such fatality because of it's purpose, i.e a gene in these chromossomes mainly affects sexual related hormone producing which do not play any role (there are exceptions like steroid hormones) in general metabolism or imune responses so a mutation in those genes or a duplication of chromossomes does not cause the death of the individual and it survives during the embryonic and fetal stages becoming later a healthy individual but with serious sexual problems like infertility and sterility . In the other hand, a mutation or duplication in autosomal chromossomes is likely dangerous to survival of the organism and many times it cannot survive in the early stages. Those who survive many times face serious health problems in their life because unlike sexual activity, autosomal gene functions are necessary for cells to survive. Sexual activity is just a way to pass genes between generations not to survive in one generation !

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  • $\begingroup$ the fact that a trisomy 21 results in serious mental and physical disabilities proves that "i.e a gene in these chromossomes mainly affects sexual related hormone producing...] is not true. $\endgroup$ – AliceD Mar 20 '15 at 1:54

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