Practical Impact Of The T2T Reference

[Webmaster]

When the Telomere-to-Telomere (T2T) Consortium announced they had finally sequenced the entirety of the Y chromosome of a human male back in February 2022, it was exciting news but there appeared to be no immediate benefit to genetic genealogy until now. YFull has started analyzing new Nebula Genomics 30X WGS (Deep) tests against the CP086569.2 (T2T) reference. This is the initial stage. They plan to start offering the same kind of analysis first for FTDNA BigY 700 tests and then later for YSEQ 30X WGS tests. It is assumed that the FTDNA tests will require the extra US$99 BAM file and not the free VCF. They will also offer re-analyses of older kits against the CP086569.2 (T2T) reference. The exact time frame for these services is not clear yet. I suspect it will depend on how well the new Nebula Genomics analyses progresses.

So why does this matter? It is significant because YFull is seeing coverage of the Y chromosome almost doubled! YFull statistics show that typically using the current GRCh38.p14 (hg38) reference:

• A 30X WGS test has a coverage of ~23.5 Mbp (million base pairs)
• A BigY 700 test has a coverage of ~18.5 Mbp

The GRCh38.p14 (hg38) reference shows the Y chromosome has a length of 57264655 bp or ~57 Mbp and the CP086569.2 (T2T) reference shows it has a length of 62460029 bp or ~62 Mbp. So by using current the GRCh38.p14 (hg38) reference we are only able to examine ~1/3 of the Y chromosome with a 30X WGS test and significantly less than that with a BigY 700 test.

BUT!

Using the CP086569.2 (T2T) reference, YFull is now showing coverage of ~45 Mbp, or over 2/3 of the Y chromosome. This has the potential of almost doubling the number of mutations that are detected. The only potential drawback to the CP086569.2 (T2T) reference is that it was derived from a J1-M267+ Ashkenazi man. There were significant changes in the basic Y chromosome structure between the J1 haplogroup and our R1b haplogroup.

A second, less publicized, T2T reference was also released about the same time. This is the CM034974.1 reference that was derived from an R1b-DF27+ Puerto Rican man. This is a much better match for R1b-M222+ men than the J1-M267 derived CP086569.2 (T2T) reference is. The CM034974.1 reference shows the Y chromosome has a length of 62480187 bp, or is 20158 bp longer than the CP086569.2 (T2T) reference. This is not counting the actual sequence difference between the 2 references.

Whether or not analysis against the CM034974.1 reference will ever become available is very much up in the air. But even using the less ideal CP086569.2 (T2T) reference is already providing much better granularity and insight. Exciting days!