Thanks again Raymond.? Nice to have a few more ancient dna!? I was thinking there might be some overlap with the ancient remains being used for the Barrie et al study because of the CGG labels.? I look forward to your spreadsheet updates.
|
There are 10 individuals in this paper who fall under U106. They all are dated between 1000 AD to as recent as the 18th Century, CGG100454 was dated 1536-1806 so will not be included in the ancient DNA spreadsheet I maintain. Only six of these individuals will be appearing as the rest are too recent (Post-medieval).
Ray
The Barrie . paper is actually a different paper.??I just downloaded the supplementary material and will need to extract the U106+ individuals from it.
Ray
I've been watching my Ancient Connections under Family Tree DNA's Discover reports to see if they add any samples from this new study to my list of connections.? I just noticed they have one sample they called?Vor Frue Kirkeg?rd 454 which is apparently ancient dna sample?CGG100454_4 from Barrie et al. 2024.? I see William Barrie was one of the contributors to the McColl et all 2024 study this thread refers to.? McColl et al has a lot of samples starting with CGG.? Could CGG100454_4 be one of the samples we've been waiting for more detailed information on from McColl et al 2024?
I don't see CGG100454_4 listed in Raymond Wing's spreadsheet.? I assume he would be sub U106 to be one of my ancient connections as I am R-FTE9331 which is sub R-FGC12993/R-A321.
|
The Barrie . paper is actually a different paper.??I just downloaded the supplementary material and will need to extract the U106+ individuals from it.
Ray
I've been watching my Ancient Connections under Family Tree DNA's Discover reports to see if they add any samples from this new study to my list of connections.? I just noticed they have one sample they called?Vor Frue Kirkeg?rd 454 which is apparently ancient dna sample?CGG100454_4 from Barrie et al. 2024.? I see William Barrie was one of the contributors to the McColl et all 2024 study this thread refers to.? McColl et al has a lot of samples starting with CGG.? Could CGG100454_4 be one of the samples we've been waiting for more detailed information on from McColl et al 2024?
I don't see CGG100454_4 listed in Raymond Wing's spreadsheet.? I assume he would be sub U106 to be one of my ancient connections as I am R-FTE9331 which is sub R-FGC12993/R-A321.
|
I've been watching my Ancient Connections under Family Tree DNA's Discover reports to see if they add any samples from this new study to my list of connections.? I just noticed they have one sample they called?Vor Frue Kirkeg?rd 454 which is apparently ancient dna sample?CGG100454_4 from Barrie et al. 2024.? I see William Barrie was one of the contributors to the McColl et all 2024 study this thread refers to.? McColl et al has a lot of samples starting with CGG.? Could CGG100454_4 be one of the samples we've been waiting for more detailed information on from McColl et al 2024?
I don't see CGG100454_4 listed in Raymond Wing's spreadsheet.? I assume he would be sub U106 to be one of my ancient connections as I am R-FTE9331 which is sub R-FGC12993/R-A321.
|
Re: Telomere? Centromere?
Thank you, Iain, for the detailed information on some of the characteristics of the Y chromosome.? Like Brian's email, I'll need to read through your message a few times to get a basic understanding, but I look forward to doing that.?
Thank you for letting me know I can look at the centromere and PAR1 and PAR2 locations on the Y chromosome through YBrowse.? I just took a look.
Appreciatively,
Mary
On Saturday, April 6, 2024 at 05:31:15 AM EDT, Iain via groups.io <gubbins@...> wrote:
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.
_._,_._,_
|
Re: Telomere? Centromere?
...oh - I see you are one of the authors, Iain!? I eagerly await the expected 2025 release!
On Saturday, April 6, 2024 at 11:55:13 AM EDT, Iain via groups.io <gubbins@...> wrote:
> 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. ...and if anyone has time and expertise to write it, that'd be great! :) ? > 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. >https://www.amazon.co.uk/Tracing-Your-Ancestors-Using-DNA-ebook/dp/B07SHHP33G Hah! We're waiting on a draft of the one remaining chapter and a few remaining issues among the other drafted chapters, so probably early 2025 by the time the publishers have had their input. ?
|
Re: Telomere? Centromere?
Thank you, Brian, for this detailed explanation - and your more understandable summary, which I needed :-) I think I sorta get the basic gist from your summary - that the centromere holds the sister chromatids together, while recombination, etc. is taking place, and thus doesn't participate in recombination(?).??
I'll read through your message a few more times and also look at the Nature article to try to get a basic understanding.
I was hoping the book link was going to be a book you had written - or you and Iain - in which case I would have submitted my order immediately :-)? I'll watch for an update of the book, though - looks like the most recent version was 2019.
With appreciation,?
Mary
On Saturday, April 6, 2024 at 09:15:55 AM EDT, Brian Swann <brian_swann@...> wrote:
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.
?
?
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.
?
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.
?
¡°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.
?
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.¡±
?
It always amazes me when this sort of thing gets investigated by X-ray crystallography, as has happened here.
?
----------
?
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.
?
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.
?
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.
?
------
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.
?
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.
?
??
|
Re: Telomere? Centromere?
> 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. ...and if anyone has time and expertise to write it, that'd be great! :) ? > 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. >https://www.amazon.co.uk/Tracing-Your-Ancestors-Using-DNA-ebook/dp/B07SHHP33G Hah! We're waiting on a draft of the one remaining chapter and a few remaining issues among the other drafted chapters, so probably early 2025 by the time the publishers have had their input. ? - Iain. ?
|
Re: Telomere? Centromere?
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.
?
?
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.
?
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.
?
¡°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.
?
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.¡±
?
It always amazes me when this sort of thing gets investigated by X-ray crystallography, as has happened here.
?
----------
?
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.
?
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.
?
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.
?
------
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.
?
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.
?
?
Brian
?
toggle quoted message
Show quoted text
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
|
Re: 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.
|
Hi, all!
In follow up to my question about determining the location of a SNP on the Y chromosome, I've been poking around Y Browse (thank you, again, for pointing me to this).? My question now is - if a SNP is close to the centromere or close to the end of the Y chromosome, how do I know if it's technically considered to be at the centromere or the telomere?? Are the telomeres delineated by exact location?? Or is it more vaguely defined as being in the general area?
For example, SNP BY26754 below is close to the end, but is that technically the telomere? And SNP?BY26110 is close to the centromere - is it technically considered to be at the centromere? Thank you!
Mary
|
Wow!? Lots for me to absorb, Vince!? Thank you so much for providing the links to the detail on the Y chromosome centromere.? This helps me visualize the issues with mapping in the centromere and specifically with?BY26995.
Appreciatively,
Mary
On Thursday, March 28, 2024 at 09:20:56 PM EDT, vince@... <vince@...> wrote:
HI Mary, Ybrowse.org lists the various cytobands for the Y-chromosome here: Specifically for the centromere, build hg38 index range chrY:10072351..11686750 You can view the hg38 reference nucleotides for this range either at Ybrowse: https://ybrowse.org/gb2/gbrowse/chrY/?plugin=FastaDumper;plugin_action=Go;view_start=10072351;view_stop=11686750 or NCBI: https://www.ncbi.nlm.nih.gov/nuccore/NC_000024.10?report=fasta&from=10072351&to=11686750 As you scroll through the sequence, you'll notice that there are: (1) several regions of populated by N's, resulting from indeterminate gaps in this assembly where mapping is not available, and (2) many swaths of repeating or highly similar motifs, making accurate mapping of short sequences (such as the 100 nucleotide base-pair fragments generated by Big-Y) problematic. For the 1001 nucleotide long sub-region containing BY26995 (chrY:10744351) : https://ybrowse.org/gb2/gbrowse/chrY/?plugin=FastaDumper;plugin_action=Go;view_start=10743851;view_stop=10744851 you can see both these issues at play. -- Best regards, Vince T.
_._,_._,_
|
HI Mary,
Ybrowse.org lists the various cytobands for the Y-chromosome here:
Specifically for the centromere, build hg38 index range chrY:10072351..11686750
You can view the hg38 reference nucleotides for this range either at
Ybrowse: https://ybrowse.org/gb2/gbrowse/chrY/?plugin=FastaDumper;plugin_action=Go;view_start=10072351;view_stop=11686750
or NCBI: https://www.ncbi.nlm.nih.gov/nuccore/NC_000024.10?report=fasta&from=10072351&to=11686750
As you scroll through the sequence, you'll notice that there are: (1) several regions of populated by N's, resulting from indeterminate gaps in this assembly where mapping is not available, and (2) many swaths of repeating or highly similar motifs, making accurate mapping of short sequences (such as the 100 nucleotide base-pair fragments generated by Big-Y) problematic.
For the 1001 nucleotide long sub-region containing BY26995 (chrY:10744351) : https://ybrowse.org/gb2/gbrowse/chrY/?plugin=FastaDumper;plugin_action=Go;view_start=10743851;view_stop=10744851
you can see both these issues at play.
--
Best regards,
Vince T.
|
Thank you for the information you shared, Brian!? I knew the PAR regions of the X and Y chromosomes can undergo recombination but didn't realize the centromeres of a male's X and Y could also recombine.? That makes sense, then, that the instability referenced has to do with recombination
Mary
On Wednesday, March 27, 2024 at 02:50:17 AM EDT, Brian Swann <brian_swann@...> wrote:
Hi Mary
?
I think this makes sense.? We are talking about different domains of the Y-Chromosome.
?
The PAR regions are at the ends of the X- and Y-Chromosomes, whereas as its name suggests the centromere is at that pinch point between the long arms and the short arms of the
chromosomes. Recent work on cell biology has done a lot of work to examine in detail how the centromere and associated cell features such as histones and chromatin go to form the mitotic spindle, which is the cell apparatus which pulls the two sets of chromosomes
apart when copying has been completed.
?
During this copying process the genes from the father and mother get shuffled (recombination) ¨C except for certain regions of the Y-Chromosome.? That is what enables us to track
male lines with surnames. But that shuffling can happen in the PAR regions, and I think in areas around the centromere too.
?
Somewhere, I have listed out the ¡°start¡± and ¡°stop¡± marker positions of the human reference Y-Chromosome sequence which relates to the various domains of the Y-Chromosome.? This
is all moderately simple until you start to ask cell biology type questions ¨C like ¡°What really determines marker mutation rates¡±, or ¡°How does the Y-Chromosome really get copied¡±. ?Or ¡°Is the Y Chromosome relevant to any medical problems outside of fertility-type
problems¡±; ¡°What is the function of that huge tail of heterochromatin on the Y-Chromosome, if anything¡±.
??
??
|
23andMe Raw DNA Data Download Instructions
FYI:
Update from 23andMe DNA: Anyone with files from this company can once again?.
https://mytrueancestry.com/en/23Upload.html
|
Hi Mary
?
I think this makes sense.? We are talking about different domains of the Y-Chromosome.
?
The PAR regions are at the ends of the X- and Y-Chromosomes, whereas as its name suggests the centromere is at that pinch point between the long arms and the short arms of the
chromosomes. Recent work on cell biology has done a lot of work to examine in detail how the centromere and associated cell features such as histones and chromatin go to form the mitotic spindle, which is the cell apparatus which pulls the two sets of chromosomes
apart when copying has been completed.
?
During this copying process the genes from the father and mother get shuffled (recombination) ¨C except for certain regions of the Y-Chromosome.? That is what enables us to track
male lines with surnames. But that shuffling can happen in the PAR regions, and I think in areas around the centromere too.
?
Somewhere, I have listed out the ¡°start¡± and ¡°stop¡± marker positions of the human reference Y-Chromosome sequence which relates to the various domains of the Y-Chromosome.? This
is all moderately simple until you start to ask cell biology type questions ¨C like ¡°What really determines marker mutation rates¡±, or ¡°How does the Y-Chromosome really get copied¡±. ?Or ¡°Is the Y Chromosome relevant to any medical problems outside of fertility-type
problems¡±; ¡°What is the function of that huge tail of heterochromatin on the Y-Chromosome, if anything¡±.
?
Trust this helps a bit.? The one thing for sure in this field is at present you never stop learning.
?
Brian
?
toggle quoted message
Show quoted text
From: [email protected] <[email protected]>
On Behalf Of mlh via groups.io
Sent: Tuesday, March 26, 2024 4:02 PM
To: [email protected]
Subject: Re: [R1b-U106] Find location of SNP
?
Thank you, Brian and Vince, for additional information on this question.? I'm enjoying the additional discussion.
One of the reasons I asked the question was because of this response from the FTDNA helpdesk regarding a Y test:
The?T>C BY26995..."mutation is in a region that's less that ideal for genetic genealogy, in the centromere. We can think of the centromere as the region where the two chromatids (the two chromosomes, one from each parent) cross with
each other, leading to "cross mutations" that are not useful for paternal genetic genealogy."
I understand Vince's point that the X and Y (23rd chromosomes for a male) only recombine in the pseudoautosomal regions (PAR). But then does the comment above about the Y mutation being in the centromere make sense???
On Tuesday, March 26, 2024 at 05:56:46 AM EDT, Brian Swann <brian_swann@...> wrote:
Hi Vince, All
Your comment here has sent me down a bit of a rabbit hole, Vince ¨C but quite an interesting rabbit hole.? Let me check first ¨C I am assuming your sentence ¡°Because
of this Y-SNPS found in the Y¡¯s PAR1 and PAR2 are excluded from phylogenetic classification¡± ¨C means they are not used in constructing the Haplotree of Mankind.
I clicked through the link to the pseudoautosomal regions on the X- and Y-chromosomes and rediscovered this comment.
Pairing () of the X and Y chromosomes and crossing over ()
between their pseudoautosomal regions appear to be necessary for the normal progression of male?.?Thus, those cells in which X-Y recombination does not occur will fail to complete meiosis.
Structural and/or genetic dissimilarity (due to??or?) between the pseudoautosomal
regions of the X and Y chromosomes can disrupt pairing and recombination, and consequently cause male infertility.
I guess this is sister chromatid exchange in action in these two PAR regions.
This shows that these pseudoautosomal regions are key regions as to how the Y-chromosome actually gets copied. Even if they are excluded from constructing the Haplotree of Mankind.
That then took me to this diagram, as to what genes and proteins are coded for by the PAR1 and PAR2 regions.? This is a composite diagram from the Wiki entry.
The genes here which caught my eye ¨C and are also commented on in the Wiki entry ¨C are the IL3R (Interleukin 3 Receptor) and the IL9R (Interleukin 9 Receptor).
That led me to find out what on earth was YWHAZ ¨C and that is an interesting, separate rabbit hole.
If I just show the first paragraph of the Wiki entry for YWHAZ:
14-3-3 protein zeta/delta?(14-3-3¦Æ) is a??that in humans is encoded by the?YWHAZ??on
chromosome 8.?The protein encoded by this gene is a member of the??family and a central hub protein for many??pathways.?14-3-3¦Æ is a major regulator of??pathways critical to cell survival and plays a key role in a number of??and?.
If you drill down this article on YWHAZ you get to the paragraphs which discuss its Clinical Significance.? That is worth reading.
Again, what caught my eye was the last paragraph, as I know most about this area of biology.
Furthermore, recent studies have shown the 14-3-3¦Æ plays a significant clinical role in the suppression of the RA symptoms in experimental animals. The 14-3-3¦Æ KO [Knock Out] animals had early onset and severe inflammatory
arthritis compared to wild-type. A significantly greater bone loss and immune cell infiltration in the synovial joints was observed in the arthritic 14-3-3¦Æ KO animals. It plays an active role in promoting collagen synthesis and bone preservation, thereby
significantly impacting bone remodelling. Rescue with antibodies failed to suppress the arthritis, however, a 14-3-3¦Æ immunization in pre-symptomatic rats, both KO and wild type, resulted in significant suppression of the arthritis. Mechanistically, it was
observed that 14-3-3¦Æ downregulates IL-1¦Â and upregulates the IL-1 receptor antagonist, which results in arthritis suppression.
The bottom line to me is that these pseudoautosomal regions of the Y chromosome may not be important for genetic genealogy ¨C but look to be pretty important indeed to measure if you are interested in human disease
conditions, how cell division happens and is controlled ¨C including regulatory control of some key cytokines and their corresponding cell receptors.
I have the feeling that without long read DNA technology it is very difficult to distinguish between the PAR1 and PAR2 regions of the X-Chromosome versus the Y-Chromosome and I may even have papers on that buried
in my archives.
But like much scientific progress in this area ¨C until you can measure something, it is pretty difficult to say anything useful about its clinical significance.
Brian
The only quibble I have with the diagram of the Y chromosome in Iain's outdated primer is that he illustrates the Y-chromosome as a diploid
genome connected at the centromere, which is correct for every other chromosome including the XX in females, but not the Y in males, or even XXY for those with
Klinefelter syndrome!? The Y chromsome is a haploid genome and generally never undergoes recombination during meiosis; it comes down to basic physical geometry - just look at the
.
There is some evidence of the X and Y conjoining during meiosis, but they conjoin at the ends near the
like an elongated "D" shape, exchanging parts of their respective
(PAR), but not at the centromere in the twinned chromatid "X" shape.? Because of this Y-SNPS found in the Y's PAR1 and PAR2 are excluded
from phylogenetic classification.
Ybrowse.org shows the linear geometry of the Y chromosome correctly.
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Thank you for your explanation, Iain, and the link to the Nature article!
From your explanation, it sounds like the issue is extremely long STRs in the Y chromosome centromere, rather than "cross mutations", as explained by FTDNA?? Is the FTDNA explanation not quite correct, at least for the Y chromosome?
We can think of the centromere as the region where the two chromatids (the two chromosomes, one from each parent) cross with each other, leading to "cross mutations" that are not useful for paternal genetic genealogy."
Thank you!
Mary
On Tuesday, March 26, 2024 at 01:35:28 PM EDT, Iain via groups.io <gubbins@...> wrote:
Hi Mary, Yes, that's right. Since men get an X from their mother and a Y from their father, and since (outside the PAR regions) they don't recombine, the centromere is still part of the male-specific Y-chromosome (MSY) region that is passed uniquely from father to son. Brian, Vince, or someone might be able to add extra biology to those statements - I'll keep myself safely on the statistical side. The centromere is, however, highly repetitive. In some senses, these repetitive sections behave like giant STRs. The BigY test breaks down DNA into sections of around 100 base pairs in length, which is shorter than the 171-base-pair repeats on the centromere. This means that it is difficult or impossible to reliably match a segment with a particular mutation back to its original position on the Y chromosome, and segments can often be confused between regions with and without the mutation. This shows up in the BigY VCF files as a low mapping quality (MQ), and means that SNPs in the centromere normally can't be treated as reliable. Sometimes a read comes through with sufficiently high MQ for it to be reported as a potential SNP. However, the statistics on MQ are based on a particular reference sequence, which is incomplete, and does not account for potential large-scale variation in the chromosome's structure, which we now now happens frequently. For genetic genealogy purposes, this makes SNPs in the centromere (and similar regions like DYZ19 and Yq12) unreliable tracers, as they can flip on and off even between two tests of the same person. However, there is a wide gradient of reliability, and some SNPs in these regions can be stable enough that they can be used in phylogenetic work (e.g., creating haplotrees) if treated carefully. If you want some further reading, here's an interesting article on the first sequence of the Y centromere:
https://www.nature.com/articles/nbt.4109 Cheers, Iain.
_._
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Hi Mary, Yes, that's right. Since men get an X from their mother and a Y from their father, and since (outside the PAR regions) they don't recombine, the centromere is still part of the male-specific Y-chromosome (MSY) region that is passed uniquely from father to son. Brian, Vince, or someone might be able to add extra biology to those statements - I'll keep myself safely on the statistical side. The centromere is, however, highly repetitive. In some senses, these repetitive sections behave like giant STRs. The BigY test breaks down DNA into sections of around 100 base pairs in length, which is shorter than the 171-base-pair repeats on the centromere. This means that it is difficult or impossible to reliably match a segment with a particular mutation back to its original position on the Y chromosome, and segments can often be confused between regions with and without the mutation. This shows up in the BigY VCF files as a low mapping quality (MQ), and means that SNPs in the centromere normally can't be treated as reliable. Sometimes a read comes through with sufficiently high MQ for it to be reported as a potential SNP. However, the statistics on MQ are based on a particular reference sequence, which is incomplete, and does not account for potential large-scale variation in the chromosome's structure, which we now now happens frequently. For genetic genealogy purposes, this makes SNPs in the centromere (and similar regions like DYZ19 and Yq12) unreliable tracers, as they can flip on and off even between two tests of the same person. However, there is a wide gradient of reliability, and some SNPs in these regions can be stable enough that they can be used in phylogenetic work (e.g., creating haplotrees) if treated carefully. If you want some further reading, here's an interesting article on the first sequence of the Y centromere:
https://www.nature.com/articles/nbt.4109 Cheers, Iain.
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Hi, all!
Thank you, Brian and Vince, for additional information on this question.? I'm enjoying the additional discussion.
One of the reasons I asked the question was because of this response from the FTDNA helpdesk regarding a Y test:
The?T>C BY26995..."mutation is in a region that's less that ideal for genetic genealogy, in the centromere. We can think of the centromere as the region where the two chromatids (the two chromosomes, one from each parent) cross with each other, leading to "cross mutations" that are not useful for paternal genetic genealogy."
I understand Vince's point that the X and Y (23rd chromosomes for a male) only recombine in the pseudoautosomal regions (PAR). But then does the comment above about the Y mutation being in the centromere make sense???
Thank you!
Mary
On Tuesday, March 26, 2024 at 05:56:46 AM EDT, Brian Swann <brian_swann@...> wrote:
Hi Vince, All
?
Your comment here has sent me down a bit of a rabbit hole, Vince ¨C but quite an interesting rabbit hole.? Let me check first ¨C I am assuming your sentence ¡°Because
of this Y-SNPS found in the Y's PAR1 and PAR2 are excluded from phylogenetic classification¡± ¨C means they are not used in constructing the Haplotree of Mankind.
I clicked through the link to the pseudoautosomal regions on the X- and Y-chromosomes and rediscovered this comment.
?
Pairing () of the X and Y chromosomes and crossing over ()
between their pseudoautosomal regions appear to be necessary for the normal progression of male?.?Thus,
those cells in which X-Y recombination does not occur will fail to complete meiosis. Structural and/or genetic dissimilarity (due to??or?)
between the pseudoautosomal regions of the X and Y chromosomes can disrupt pairing and recombination, and consequently cause male infertility.
?
I guess this is sister chromatid exchange in action in these two PAR regions.
?
This shows that these pseudoautosomal regions are key regions as to how the Y-chromosome actually gets copied. Even if they are excluded from constructing the Haplotree of Mankind.
?
That then took me to this diagram, as to what genes and proteins are coded for by the PAR1 and PAR2 regions.? This is a composite diagram from the Wiki entry.
?
?
The genes here which caught my eye ¨C and are also commented on in the Wiki entry ¨C are the IL3R (Interleukin 3 Receptor) and the IL9R (Interleukin 9 Receptor).
?
?
That led me to find out what on earth was YWHAZ ¨C and that is an interesting, separate rabbit hole.
?
?
If I just show the first paragraph of the Wiki entry for YWHAZ:
?
14-3-3 protein zeta/delta?(14-3-3¦Æ)
is a??that
in humans is encoded by the?YWHAZ??on chromosome 8.?The protein
encoded by this gene is a member of the??family
and a central hub protein for many??pathways.?14-3-3¦Æ
is a major regulator of??pathways
critical to cell survival and plays a key role in a number of??and?.
?
If you drill down this article on YWHAZ you get to the paragraphs which discuss its Clinical Significance.? That is worth reading.
?
Again, what caught my eye was the last paragraph, as I know most about this area of biology.
?
Furthermore, recent studies have shown the 14-3-3¦Æ plays a significant clinical role in the suppression of the RA symptoms in experimental animals.
The 14-3-3¦Æ KO [Knock Out] animals had early onset and severe inflammatory arthritis compared to wild-type. A significantly greater bone loss and immune cell infiltration in the synovial joints was observed in the arthritic 14-3-3¦Æ KO animals. It plays an
active role in promoting collagen synthesis and bone preservation, thereby significantly impacting bone remodelling. Rescue with antibodies failed to suppress the arthritis, however, a 14-3-3¦Æ immunization in pre-symptomatic rats, both KO and wild type, resulted
in significant suppression of the arthritis. Mechanistically, it was observed that 14-3-3¦Æ downregulates IL-1¦Â and upregulates the IL-1 receptor antagonist, which results in arthritis suppression.
?
The bottom line to me is that these pseudoautosomal regions of the Y chromosome may not be important for genetic genealogy ¨C but look to be pretty important indeed to measure
if you are interested in human disease conditions, how cell division happens and is controlled ¨C including regulatory control of some key cytokines and their corresponding cell receptors.
?
I have the feeling that without long read DNA technology it is very difficult to distinguish between the PAR1 and PAR2 regions of the X-Chromosome versus the Y-Chromosome and
I may even have papers on that buried in my archives.
?
But like much scientific progress in this area ¨C until you can measure something, it is pretty difficult to say anything useful about its clinical significance.
?
Brian
?
?
The only quibble I have with the diagram of the Y chromosome in Iain's outdated primer is that he illustrates the Y-chromosome as a diploid
genome connected at the centromere, which is correct for every other chromosome including the XX in females, but not the Y in males, or even XXY for those with
Klinefelter syndrome!? The Y chromsome is a haploid genome and generally never undergoes recombination during meiosis; it comes down to basic physical geometry - just look at the
.
There is some evidence of the X and Y conjoining during meiosis, but they conjoin at the ends near the
like an elongated "D" shape, exchanging parts of their respective
(PAR), but not at the centromere in the twinned chromatid "X" shape.? Because of this Y-SNPS found in the Y's PAR1 and PAR2 are excluded
from phylogenetic classification.
Ybrowse.org shows the linear geometry of the Y chromosome correctly.
|
Hi Vince, All
?
Your comment here has sent me down a bit of a rabbit hole, Vince ¨C but quite an interesting rabbit hole.? Let me check first ¨C I am assuming your sentence ¡°Because
of this Y-SNPS found in the Y's PAR1 and PAR2 are excluded from phylogenetic classification¡± ¨C means they are not used in constructing the Haplotree of Mankind.
I clicked through the link to the pseudoautosomal regions on the X- and Y-chromosomes and rediscovered this comment.
?
Pairing () of the X and Y chromosomes and crossing over ()
between their pseudoautosomal regions appear to be necessary for the normal progression of male?.?Thus,
those cells in which X-Y recombination does not occur will fail to complete meiosis. Structural and/or genetic dissimilarity (due to??or?)
between the pseudoautosomal regions of the X and Y chromosomes can disrupt pairing and recombination, and consequently cause male infertility.
?
I guess this is sister chromatid exchange in action in these two PAR regions.
?
This shows that these pseudoautosomal regions are key regions as to how the Y-chromosome actually gets copied. Even if they are excluded from constructing the Haplotree of Mankind.
?
That then took me to this diagram, as to what genes and proteins are coded for by the PAR1 and PAR2 regions.? This is a composite diagram from the Wiki entry.
?
?
The genes here which caught my eye ¨C and are also commented on in the Wiki entry ¨C are the IL3R (Interleukin 3 Receptor) and the IL9R (Interleukin 9 Receptor).
?
?
That led me to find out what on earth was YWHAZ ¨C and that is an interesting, separate rabbit hole.
?
?
If I just show the first paragraph of the Wiki entry for YWHAZ:
?
14-3-3 protein zeta/delta?(14-3-3¦Æ)
is a??that
in humans is encoded by the?YWHAZ??on chromosome 8.?The protein
encoded by this gene is a member of the??family
and a central hub protein for many??pathways.?14-3-3¦Æ
is a major regulator of??pathways
critical to cell survival and plays a key role in a number of??and?.
?
If you drill down this article on YWHAZ you get to the paragraphs which discuss its Clinical Significance.? That is worth reading.
?
Again, what caught my eye was the last paragraph, as I know most about this area of biology.
?
Furthermore, recent studies have shown the 14-3-3¦Æ plays a significant clinical role in the suppression of the RA symptoms in experimental animals.
The 14-3-3¦Æ KO [Knock Out] animals had early onset and severe inflammatory arthritis compared to wild-type. A significantly greater bone loss and immune cell infiltration in the synovial joints was observed in the arthritic 14-3-3¦Æ KO animals. It plays an
active role in promoting collagen synthesis and bone preservation, thereby significantly impacting bone remodelling. Rescue with antibodies failed to suppress the arthritis, however, a 14-3-3¦Æ immunization in pre-symptomatic rats, both KO and wild type, resulted
in significant suppression of the arthritis. Mechanistically, it was observed that 14-3-3¦Æ downregulates IL-1¦Â and upregulates the IL-1 receptor antagonist, which results in arthritis suppression.
?
The bottom line to me is that these pseudoautosomal regions of the Y chromosome may not be important for genetic genealogy ¨C but look to be pretty important indeed to measure
if you are interested in human disease conditions, how cell division happens and is controlled ¨C including regulatory control of some key cytokines and their corresponding cell receptors.
?
I have the feeling that without long read DNA technology it is very difficult to distinguish between the PAR1 and PAR2 regions of the X-Chromosome versus the Y-Chromosome and
I may even have papers on that buried in my archives.
?
But like much scientific progress in this area ¨C until you can measure something, it is pretty difficult to say anything useful about its clinical significance.
?
Brian
?
toggle quoted message
Show quoted text
From: [email protected] <[email protected]>
On Behalf Of vince@...
Sent: Tuesday, March 26, 2024 4:30 AM
To: [email protected]
Subject: Re: [R1b-U106] Find location of SNP
?
The only quibble I have with the diagram of the Y chromosome in Iain's outdated primer is that he illustrates the Y-chromosome as a diploid
genome connected at the centromere, which is correct for every other chromosome including the XX in females, but not the Y in males, or even XXY for those with
Klinefelter syndrome!? The Y chromsome is a haploid genome and generally never undergoes recombination during meiosis; it comes down to basic physical geometry - just look at the
.
There is some evidence of the X and Y conjoining during meiosis, but they conjoin at the ends near the
like an elongated "D" shape, exchanging parts of their respective
(PAR), but not at the centromere in the twinned chromatid "X" shape.? Because of this Y-SNPS found in the Y's PAR1 and PAR2 are excluded
from phylogenetic classification.
Ybrowse.org shows the linear geometry of the Y chromosome correctly.
Best regards,
Vince T.
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