OTOA haplotypes

[Paranchai87]

Hi there

I would like to analyze OTOA gene, but found that the naming of OTOA_hap1, OTOA_hap2, OTOA_hap3, OTOA_hap4, OTOA_hap5, etc. is confusing, as it does not differentiate between the real gene OTOA and the pseudogene OTOAP1. I looked at som samples and found that most have hap1 and hap2 as real gene, but sometimes hap2 can be OTOAP1 if there is a gene deletion. Are you aware of this issue or do I miss something?

I thank you so much in advance for answer.

Best,
Paranchai

[xiao-chen-xc]

OTOAP1 haplotypes should start with 0 if you check the final_haplotypes field in the JSON, indicating that they are truncated on one side as homology ends. In the VCF those haplotypes have the "truncated" label in HPBOUND in the INFO field.

[Paranchai87]

Hi Xiao Thanks you so much. Does it mean that for all other genes, their pseudogenes HPBOUND is tagged as truncated? Or does this only apply to some genes including OTOA? Best, Paranchai

…

________________________________ From: Xiao Chen ***@***.***> Sent: Thursday, 18 December 2025 21:32 To: PacificBiosciences/paraphase ***@***.***> Cc: Paranchai Boonsawat ***@***.***>; Author ***@***.***> Subject: Re: [PacificBiosciences/paraphase] OTOA haplotypes (Issue #63) [https://avatars.githubusercontent.com/u/14202913?s=20&v=4]xiao-chen-xc left a comment (PacificBiosciences/paraphase#63)<#63 (comment)> OTOAP1 haplotypes should start with 0 if you check the final_haplotypes field in the JSON, indicating that they are truncated on one side as homology ends. In the VCF those haplotypes have the "truncated" label in HPBOUND in the INFO field. — Reply to this email directly, view it on GitHub<#63 (comment)>, or unsubscribe<https://github.com/notifications/unsubscribe-auth/BQHUNHIJ76VJWKL35VI2JHD4CMFPLAVCNFSM6AAAAACPJW6V7KVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZTMNZSGEYTKMZUHE>. You are receiving this because you authored the thread.Message ID: ***@***.***>

[xiao-chen-xc]

Hi Paranchai,

truncated does not always imply pseudogene. You can compare the HPBOUND coordinates with the gene transcript coordinates. If a truncated HPBOUND falls within a transcript, then it means the haplotype ends in the middle of the transcript (and continues to some non-homologous sequence). This most likely implies that it comes from a pseudogene. In some rare cases, it can also indicate a big deletion in the gene. In either case, it implies a nonfunctional gene. The rationale we have for Paraphase is that we don't really need to know if a haplotype comes from the gene or the pseudogene - all we need is its functional status, which we known through annotation of its variants (pseudogenes have variants that make them nonfunctional) and its HPBOUND start/end coordinates (pseudogenes are sometimes truncated compared to the gene transcript).

Happy to have a call to discuss if you like.

Thanks,
Xiao