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Re: Telomere? Centromere?


 

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Just to give some further idea of the complexity that is involved when cells divide. This Nature paper is from 2023, but key reference papers within it go back to 2008.

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? Structural basis of centromeric cohesion protection

The gist of what the paper is about is contained within these sentences in the summary.? Very often there are acronyms used in these types of science papers which you have to spend time reading and deciphering in order to understand what on earth they are talking about.

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They often seem to assume the reader spends most of his time knee-deep in the cell biology world of how chromosomes really exchange genetic information as and when they divide, and how cells actually accomplish that.

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¡°In the early stages of mitosis, cohesin is released from chromosome arms but not from centromeres. The protection of centromeric cohesin by SGO1 maintains the sister chromatid cohesion that resists the pulling forces of microtubules until all chromosomes are attached in a bipolar manner to the mitotic spindle.

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SGO1¨Ccohesin binding is maintained until the formation of microtubule¨Ckinetochore attachments and is required for faithful chromosome segregation and the maintenance of a stable karyotype.¡±

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It always amazes me when this sort of thing gets investigated by X-ray crystallography, as has happened here.

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I interpret this as meaning the force used to pull the two pairs of chromosomes apart does not fully manifest itself and is carefully controlled until the cell has received all the signals that everything is aligned correctly on all the chromosomes, they are all attached appropriately to the mitotic spindle - and now it is safe as it will ever be to proceed onwards with cell division.

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A bit like giving birth ¨C you have to go through all those preliminary phases, but once everything has been gone through, aligned up and attached correctly ¨C there is not much point in hanging around any longer, better to proceed as fast as is reasonably possible.

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I do have a Table of the positions of the STR units on the Y Chromosome ¨C but there are still some 4 Y-STR positions on STR markers 1-111 whose locations are not flagged on Ybrowse - DYS425, DYS395S1, DYS406S1 and Y-GATA-H10.

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Iain and myself have very occasionally exchanged ideas whether there should be a book covering some of these aspects of cell biology for genetic genealogists.

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In practice, it would be sensible to wait until the update of this book appears and to take it from there.? Any such book would benefit appreciably by having some illustrations in colour.

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Brian

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From: [email protected] <[email protected]> On Behalf Of Iain via groups.io
Sent: Saturday, April 6, 2024 10:31 AM
To: [email protected]
Subject: Re: [R1b-U106] Telomere? Centromere?

Hi Mary

The biologists might again provide more accuracy, clarity and detail than I can, but. . .

To answer your earlier question, I don't think that the centromeres of the X and Y recombine like the autosomes: the centromere forms part of the male-specific Y-chromosome (MSY) and does contain inheritable Y-SNPs. The centromere's DYZ3 region contains comprised of almost exactly repeating 171 base-pair sequences, grouped into 5.8 kbp higher-order repeats. This can't be easily read by short-read technology like Big Y, which only has read lengths of 100 base pairs, so each read only captures a fraction of one of these repeats, and it's impossible to securely tell in which one a SNP is found. Equally, like Y-STRs, the number of repeats will change between individuals - we don't yet know a lot about this kind of larger-scale variation, but it is slowly being uncovered by the T2T consortium.

That doesn't mean that there is no swapping of genes between X and Y. In addition to the pseudo-autosomal regions at the end of the Y chromosome, which do recombine with the X, there is substantial gene conversion between the two chromosomes. The most familiar part of this is the X-transposed region (the several-million-base-pair regions which represents the major difference between BigY-500 and BigY-700 tests), which our Y-DNA ancestor inherited from his X chromosome about two million years ago. However, gene conversion of much smaller units of a few hundred base pairs or less occurs frequently, notably in a few gene-conversion hotspots. The rate of conversion per base pair that of the rate of Y-SNP formation within these regions. This contributes to both "flaky" SNPs and poor mapping in parts of the Big Y test, and localised differences in the mutation rate (but these average out on large scales). There is a slippery rabbit hole of information here, which requires a steep learning curve and is definitely beyond my pay grade to say much more about!

For your recent question on the definitions of the telomeres and centromeres, this depends on the reference sequence that's used. Most of the time, we refer to the hg38 (or GRCh38) reference sequence, and this is what FTDNA, YFull, etc., now use as convention anyway. As I understand it, the pseudo-autosomal regions aren't telomeres in the strict sense, but parts of the X and Y chromosomes that retain their autosomal recombination. You can find them in YBrowse by typing in their names: PAR1 and PAR2. Similarly, the centromere can be found by typing in CEN and selecting chrY, which represents the centromere in the hg38 reference. Positions are listed in the search box.

Cheers

Iain

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