Why are PAR regions in X and Y different sizes?
duartemolha opened this issue · 7 comments
duartemolha commented
Hi
I was surprised to find that the PAR regions in X and Y do not match in terms of length.
It was my understanding that PAR regions should be exactly the same size on both chromossomes
arangrhie commented
Hello,
The PARs are not expected to be exactly at the same size.
It was assumed so because it was copy-pasted that way in the GRCh reference.
Also note the X comes from CHM13, the Y comes from HG002.
The PARs are not the same size either on HG002XY, because there are a few X/Y specific variations.
You can see even from short-read variant calls, after masking the PARs on the Y and mapping / variant calling on the X-PARs, there are handful of variants called as "heterozygous".
There are more details in the T2T-Y preprint, see Fig. 3d and EDFig. 9a.
Best,
Arang
duartemolha commented
Saying that the par regions is not the same because it has variations does
not make sense to me.
That is the same as saying autossonal pairs would have different sequence
because one of them has a variation.
Their are automossal and there is crossover with every meiosis.
Does crossover not occur in PAR regions?
…On Wed, 10 May 2023, 21:40 Arang Rhie, ***@***.***> wrote:
Hello,
The PARs are not expected to be exactly at the same size.
It was assumed so because it was copy-pasted that way in the GRCh
reference.
Also note the X comes from CHM13, the Y comes from HG002.
The PARs are not the same size either on HG002XY, because there are a few
X/Y specific variations.
You can see even from short-read variant calls, after masking the PARs on
the Y and mapping / variant calling on the X-PARs, there are handful of
variants called as "heterozygous".
There are more details in the T2T-Y preprint
<https://www.biorxiv.org/content/10.1101/2022.12.01.518724v1>, see Fig.
3d and EDFig. 9a.
Best,
Arang
—
Reply to this email directly, view it on GitHub
<#81 (comment)>, or
unsubscribe
<https://github.com/notifications/unsubscribe-auth/AAFQIVJ6G4O2WF5FWLHGOVTXFP4LZANCNFSM6AAAAAAX3FCJIM>
.
You are receiving this because you authored the thread.Message ID:
***@***.***>
skoren commented
Not sure I follow your question, the autosomes are not identical in size in a diploid either. In this case, the X and Y are also from different samples/cell lines so they would never have been present in the same cell.
duartemolha commented
I think we are in disagreement because i am looking at t2t as a reference.
Maybe that is incorrect.
Grch37 and grch38 only have the sequencing of 1 chromosome 1 correct? They
are assuming the pair have the same sequence.
In humans every chromosome has a different sequence because each have
mutations. But that is not contained in the reference.
The same should be the case with the par regions for t2t.
…On Fri, 12 May 2023, 22:41 Sergey Koren, ***@***.***> wrote:
Not sure I follow your question, the autosomes are not identical in size
in a diploid either. In this case, the X and Y are also from different
samples/cell lines so they would never have been present in the same cell.
—
Reply to this email directly, view it on GitHub
<#81 (comment)>, or
unsubscribe
<https://github.com/notifications/unsubscribe-auth/AAFQIVNDVA3RIZ5SZPIJTFLXF2VABANCNFSM6AAAAAAX3FCJIM>
.
You are receiving this because you authored the thread.Message ID:
***@***.***>
ekg commented
As far as I know, the PARs are not guaranteed a crossover per meiosis. I'm
not sure what information you're working from.
It's totally natural that they have different lengths and totally unnatural
than the versions in GRC were exactly the same.
Note that T2T-CHM13 contains pseudo homologous regions (PHRs) on the
acrocentric short arms which support recombination between heterologs.
https://doi.org/10.1038/s41586-023-05976-y
In the past we would mask regions like the PARs and PHRs. Now with the
advent of diploid complete assemblies I think we will need to keep track of
them rather than trying to mask them out.
You can of course mask using the intervals, should your application depend
on having only one copy of each homologous region.
But this is a slippery problem. There are big segmental duplications of all
types which support recombination. Although it's driven by non-crossover
type or gene conversion in most cases, this will lead to homogenization and
cause all the same issues for tools that assume there is only one copy of
each locus in the reference.
…On Sat, May 13, 2023, 03:28 Duarte ***@***.***> wrote:
I think we are in disagreement because i am looking at t2t as a reference.
Maybe that is incorrect.
Grch37 and grch38 only have the sequencing of 1 chromosome 1 correct? They
are assuming the pair have the same sequence.
In humans every chromosome has a different sequence because each have
mutations. But that is not contained in the reference.
The same should be the case with the par regions for t2t.
On Fri, 12 May 2023, 22:41 Sergey Koren, ***@***.***> wrote:
> Not sure I follow your question, the autosomes are not identical in size
> in a diploid either. In this case, the X and Y are also from different
> samples/cell lines so they would never have been present in the same
cell.
>
> —
> Reply to this email directly, view it on GitHub
> <#81 (comment)>, or
> unsubscribe
> <
https://github.com/notifications/unsubscribe-auth/AAFQIVNDVA3RIZ5SZPIJTFLXF2VABANCNFSM6AAAAAAX3FCJIM
>
> .
> You are receiving this because you authored the thread.Message ID:
> ***@***.***>
>
—
Reply to this email directly, view it on GitHub
<#81 (comment)>, or
unsubscribe
<https://github.com/notifications/unsubscribe-auth/AABDQELSXDZ2VGJHE5ZZO5DXF5A4FANCNFSM6AAAAAAX3FCJIM>
.
You are receiving this because you are subscribed to this thread.Message
ID: ***@***.***>
duartemolha commented
Garanteed crossover... i do not think so.
But i do believe crossover can occur. The same with every autossomal
region in autossomal chromossomes.
Sure there are biallelic references in the pangenome. But the alignment is
not done vs each individual sample. It is done vs the graph... correct?
If we made a graph for the CHM3 there would be only 1 path through the
majority of the par regions.
But ok. I think i understand the source of my confusion.
I was thinking of references as linear ... line the ones until now.
…On Sat, 13 May 2023, 13:16 Erik Garrison, ***@***.***> wrote:
As far as I know, the PARs are not guaranteed a crossover per meiosis. I'm
not sure what information you're working from.
It's totally natural that they have different lengths and totally unnatural
than the versions in GRC were exactly the same.
Note that T2T-CHM13 contains pseudo homologous regions (PHRs) on the
acrocentric short arms which support recombination between heterologs.
https://doi.org/10.1038/s41586-023-05976-y
In the past we would mask regions like the PARs and PHRs. Now with the
advent of diploid complete assemblies I think we will need to keep track of
them rather than trying to mask them out.
You can of course mask using the intervals, should your application depend
on having only one copy of each homologous region.
But this is a slippery problem. There are big segmental duplications of all
types which support recombination. Although it's driven by non-crossover
type or gene conversion in most cases, this will lead to homogenization and
cause all the same issues for tools that assume there is only one copy of
each locus in the reference.
On Sat, May 13, 2023, 03:28 Duarte ***@***.***> wrote:
> I think we are in disagreement because i am looking at t2t as a
reference.
> Maybe that is incorrect.
>
> Grch37 and grch38 only have the sequencing of 1 chromosome 1 correct?
They
> are assuming the pair have the same sequence.
>
> In humans every chromosome has a different sequence because each have
> mutations. But that is not contained in the reference.
>
> The same should be the case with the par regions for t2t.
>
>
>
>
> On Fri, 12 May 2023, 22:41 Sergey Koren, ***@***.***> wrote:
>
> > Not sure I follow your question, the autosomes are not identical in
size
> > in a diploid either. In this case, the X and Y are also from different
> > samples/cell lines so they would never have been present in the same
> cell.
> >
> > —
> > Reply to this email directly, view it on GitHub
> > <#81 (comment)>, or
> > unsubscribe
> > <
>
https://github.com/notifications/unsubscribe-auth/AAFQIVNDVA3RIZ5SZPIJTFLXF2VABANCNFSM6AAAAAAX3FCJIM
> >
> > .
> > You are receiving this because you authored the thread.Message ID:
> > ***@***.***>
> >
>
> —
> Reply to this email directly, view it on GitHub
> <#81 (comment)>, or
> unsubscribe
> <
https://github.com/notifications/unsubscribe-auth/AABDQELSXDZ2VGJHE5ZZO5DXF5A4FANCNFSM6AAAAAAX3FCJIM
>
> .
> You are receiving this because you are subscribed to this thread.Message
> ID: ***@***.***>
>
—
Reply to this email directly, view it on GitHub
<#81 (comment)>, or
unsubscribe
<https://github.com/notifications/unsubscribe-auth/AAFQIVM4A5QATFXJHS3S52LXF53SPANCNFSM6AAAAAAX3FCJIM>
.
You are receiving this because you authored the thread.Message ID:
***@***.***>
ekg commented
In a pangenome graph built for read mapping, these regions will likely be
collapsed. That means that there will be one region of the graph with two
or more chromosomes (paths) from the same reference genome.
I say this somewhat hypothetically because we don't have many experiments
based on graphs that collapse them, but there is evidence that this
actually helps downstream applications and makes things easier for read
mapping to the pangenome.
If the graph is built without chromosome partitioning, I'd expect the
acrocentric PHRs, the PARs and the XTR to come together in this way.
Other very large segmental duplications might behave like PHRs. We need to
do the survey. If they aren't sub-telomeric, then crossover will probably
be selected out and all we will see is gene conversion. Telomeric PHRs
(like the PARs) should support crossover because the disruption to the
chromosomes involved is minimal.
…On Sun, May 14, 2023, 12:29 Duarte ***@***.***> wrote:
Garanteed crossover... i do not think so.
But i do believe crossover can occur. The same with every autossomal
region in autossomal chromossomes.
Sure there are biallelic references in the pangenome. But the alignment is
not done vs each individual sample. It is done vs the graph... correct?
If we made a graph for the CHM3 there would be only 1 path through the
majority of the par regions.
But ok. I think i understand the source of my confusion.
I was thinking of references as linear ... line the ones until now.
On Sat, 13 May 2023, 13:16 Erik Garrison, ***@***.***> wrote:
> As far as I know, the PARs are not guaranteed a crossover per meiosis.
I'm
> not sure what information you're working from.
>
> It's totally natural that they have different lengths and totally
unnatural
> than the versions in GRC were exactly the same.
>
> Note that T2T-CHM13 contains pseudo homologous regions (PHRs) on the
> acrocentric short arms which support recombination between heterologs.
> https://doi.org/10.1038/s41586-023-05976-y
>
> In the past we would mask regions like the PARs and PHRs. Now with the
> advent of diploid complete assemblies I think we will need to keep track
of
> them rather than trying to mask them out.
>
> You can of course mask using the intervals, should your application
depend
> on having only one copy of each homologous region.
>
> But this is a slippery problem. There are big segmental duplications of
all
> types which support recombination. Although it's driven by non-crossover
> type or gene conversion in most cases, this will lead to homogenization
and
> cause all the same issues for tools that assume there is only one copy of
> each locus in the reference.
>
> On Sat, May 13, 2023, 03:28 Duarte ***@***.***> wrote:
>
> > I think we are in disagreement because i am looking at t2t as a
> reference.
> > Maybe that is incorrect.
> >
> > Grch37 and grch38 only have the sequencing of 1 chromosome 1 correct?
> They
> > are assuming the pair have the same sequence.
> >
> > In humans every chromosome has a different sequence because each have
> > mutations. But that is not contained in the reference.
> >
> > The same should be the case with the par regions for t2t.
> >
> >
> >
> >
> > On Fri, 12 May 2023, 22:41 Sergey Koren, ***@***.***> wrote:
> >
> > > Not sure I follow your question, the autosomes are not identical in
> size
> > > in a diploid either. In this case, the X and Y are also from
different
> > > samples/cell lines so they would never have been present in the same
> > cell.
> > >
> > > —
> > > Reply to this email directly, view it on GitHub
> > > <#81 (comment)>,
or
> > > unsubscribe
> > > <
> >
>
https://github.com/notifications/unsubscribe-auth/AAFQIVNDVA3RIZ5SZPIJTFLXF2VABANCNFSM6AAAAAAX3FCJIM
> > >
> > > .
> > > You are receiving this because you authored the thread.Message ID:
> > > ***@***.***>
> > >
> >
> > —
> > Reply to this email directly, view it on GitHub
> > <#81 (comment)>, or
> > unsubscribe
> > <
>
https://github.com/notifications/unsubscribe-auth/AABDQELSXDZ2VGJHE5ZZO5DXF5A4FANCNFSM6AAAAAAX3FCJIM
> >
> > .
> > You are receiving this because you are subscribed to this
thread.Message
> > ID: ***@***.***>
> >
>
> —
> Reply to this email directly, view it on GitHub
> <#81 (comment)>, or
> unsubscribe
> <
https://github.com/notifications/unsubscribe-auth/AAFQIVM4A5QATFXJHS3S52LXF53SPANCNFSM6AAAAAAX3FCJIM
>
> .
> You are receiving this because you authored the thread.Message ID:
> ***@***.***>
>
—
Reply to this email directly, view it on GitHub
<#81 (comment)>, or
unsubscribe
<https://github.com/notifications/unsubscribe-auth/AABDQENALVLQSGOV4X7C7VTXGCXYLANCNFSM6AAAAAAX3FCJIM>
.
You are receiving this because you commented.Message ID:
***@***.***>