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This is ready for review. The main thing I am unsure of is how I described the differing locus definitions. |
Update evidence and genomic coordinates for SCA_EP400 ep400 provisional liftover adding family 2 Update data add family 2 info Update data fix nomad Update data add description Update data ep400 nuance Update data add exon fix actually fix this time clarify broad range why is year a string and not an int? Update data show alternate locus definition
hdashnow
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hdashnow
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I suggested some rewording for details and have a few minor items that might need your follow-up
| "details": "Disease link reported in Danzi et al. Family 1 (father and daughter) had a longest pure tract of 56-58 repeats, while Family 2 (mother-son, mother ungenotyped) had 75 pure CAG repeats. STRchive is using the broad locus definition of chr12:132062524-132062611, where the reference locus structure is (CAG)6-(CAA)2-(CAG)14-(CAA)1-(CAG)4-(CAA)1-(CAG)1. A narrower locus definition of chr12:132062548-132062611 has also been used to describe this locus and results in a differently described pathogenic range [@doi:10.1101/2025.01.06.631535].", | ||
| "detection": "Long-read sequencing with targeted sanger confirmation has detected expansions in this locus [@doi:10.1101/2025.01.06.631535].", | ||
| "mechanism": "Unknown", | ||
| "mechanism_detail": "Polyglutamine expansion", |
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Citations for mechanism detail? Also, is there a value for "mechanism"?
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There is not a value for mechanism. We only know the mechanisms of similar loci and the mechanism of other EP400 mutations. There isn't mechanistic information for this one. I'll delete the detail part since it might be misinterpreted as toxic polyQ GoF
| "typ_age_onset_min": null, | ||
| "typ_age_onset_max": null, | ||
| "details": "Disease link reported in Danzi et al. Family 1 (father and daughter) had a longest pure tract of 56-58 repeats, while Family 2 (mother-son, mother ungenotyped) had 75 pure CAG repeats. STRchive is using the broad locus definition of chr12:132062524-132062611, where the reference locus structure is (CAG)6-(CAA)2-(CAG)14-(CAA)1-(CAG)4-(CAA)1-(CAG)1. A narrower locus definition of chr12:132062548-132062611 has also been used to describe this locus and results in a differently described pathogenic range [@doi:10.1101/2025.01.06.631535].", | ||
| "detection": "Long-read sequencing with targeted sanger confirmation has detected expansions in this locus [@doi:10.1101/2025.01.06.631535].", |
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Didn't they use ExpansionHunter on short reads as well? For controls? This was the stated reason for using the narrow locus definition I think.
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They did in the controls. We do not know if short read is able to actually detect this expansion (from this paper at least) since the affected individuals were flagged from long read. I could put info that it is useful for controls, though the convention for other detection fields has been about detecting the expansion. What do you think?
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If it's not in the other loci, I think it's probably fine to skip it.
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Looks like the benign range should be 8-21 pure CAGs based on the population data (not sure if I'm reading those off the plot right!). If we assume the reference locus structure, that would be (CAG)6(CAA)2(CAG)8-21(CAA)1(CAG)4(CAA)(CAG) Correction: Update: |
…ge to include the length with interruptions.
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Description
Summarize the changes
Fixes: #480
Major Changes
Minor Changes
Checklist
CITATION.cff, format X.Y.Z. If any major changes, increment Y. If only minor changes, increment Z. If the breaking change (rare), increment X.