The absence of CFHR3 and CFHR1 genes from the T2T-CHM13 assembly can limit the molecular diagnosis of complement-related diseases

Impact of genome build on RNA-seq interpretation and diagnostics

“…For example, hg19 and hg38-expressed CFHR-Factor H complex genes CFHR1 and CFHR3 are linked with atypical hemolytic uremic syndrome 36, 37 and fall within a region harboring population-specific copy number variations. The absence of these genes in CHM13 could be due to the reliance on a single cell line, especially in contrast to the genetic diversity from multiple cell lines underlying hg38 38 . We detected quantification of CFHR1 in fibroblast and muscle, and CFHR3 in iPS and iPS neural progenitor cells for hg19 and hg38.…”

“…We detected quantification of CFHR1 in fibroblast and muscle, and CFHR3 in iPS and iPS neural progenitor cells for hg19 and hg38. One study reports that detection of the disease-causing structural variants was not possible when aligning to CHM13, even with long-read sequencing 38 , suggesting CFHR-Factor H complex disorders should not be evaluated using CHM13v2. The absence of these genes in CHM13v2 likely influences mapping in CHM13 of other CFHR-Factor H complex genes – CFHR4 (also linked to atypical hemolytic uremic syndrome) is detected as quantified only in CHM13 in iPSC NPC with a median TPM of 4.4.…”