No HTT repeat in adotto_TRregions_v1.2 ?

[davidlougheed]

Hello,
I'm working on benchmarking some tandem repeat genotypers and I was looking for the well-known pathogenic CAG HTT repeat in the adotto_TRregions_v1.2.bed BED file.
However, there doesn't seem to be an entry for the CAG repeat in the BED file. Is this just because it doesn't vary from HG38 in HG002?

[ACEnglish]

Hello,

The region we have documented for HTT from our Patho.csv is at

chr4	3074876	3074966	HTT	CAG

This intersects in the adotto_TRregions_v1.2:

chr4	3074938	3075085

Which is included as a tier1 region in the GIAB TR v1.0

chr4	3074938	3075085	Tier1	TN_TN_TN	14	0.7933	-4	0	28

So there perhaps is a discrepancy in the boundaries between the catalog and the patho.csv by 62bp which may be messing up your query region's overlap to the catalog?

[davidlougheed]

Thanks for the quick response! I do see that region in adotto_TRregions_v1.2, as the following line:

chr4	3074938	3075085	5	0	25	10	3	2	2	93	98	.	HTT	.	25	protein_coding	"[{""chrom"": ""chr4"", ""start"": 3074938, ""end"": 3075048, ""period"": 3.0, ""copies"": 37.0, ""score"": 143, ""entropy"": 1.5, ""ovl_flag"": 4, ""motif"": ""GCC"", ""purity"": 91}, {""chrom"": ""chr4"", ""start"": 3075050, ""end"": 3075060, ""period"": 5.0, ""copies"": 2.2, ""score"": 33, ""entropy"": 0.95, ""ovl_flag"": 1, ""motif"": ""CCCGG"", ""purity"": 95}]"

However, I was expecting to see the CAG repeat as an entry in the anno column of the BED file, since it's the best-known expansion location and motif for HTT repeat variation, with the GCC coming after.

My goal is to produce a BED file with motifs to feed to various STR genotypers, so extracting this chr4:3074938-3075048 region from hg38 gives a more heterogeneous repeat then what I would expect (and is missing a repeat I'd like to have), which would be two STR entries: CAG in chr4:3074877-3074940, and GCC in ~chr4:3074941-3075052.