VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease - Sorbonne Université Access content directly
Journal Articles iScience Year : 2023

VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease

Hassan Saei
  • Function : Author
Vincent Morinière
  • Function : Author
Laurence Heidet
  • Function : Author
Olivier Gribouval
  • Function : Author
Frederic Tores
  • Function : Author
Manon Mautret-Godefroy
  • Function : Author
Bertrand Knebelmann
  • Function : Author
Vincent Vuiblet
Corinne Antignac
Patrick Nitschké
  • Function : Author
Guillaume Dorval
  • Function : Author

Abstract

The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease-MUC1 (ADTKD-MUC1) is caused by specific frameshift variants in the coding VNTR of the MUC1 gene. Calling variants from VNTR using short-read sequencing (SRS) is challenging due to poor read mappability. We developed a computational pipeline, VNtyper, for reliable detection of MUC1 VNTR pathogenic variants and demonstrated its clinical utility in two distinct cohorts: (1) a historical cohort including 108 families with ADTKD and (2) a replication naive cohort comprising 2,910 patients previously tested on a panel of genes involved in monogenic renal diseases. In the historical cohort all cases known to carry pathogenic MUC1 variants were re-identified, and a new 25bp-frameshift insertion in an additional mislaid family was detected. In the replication cohort, we discovered and validated 30 new patients.

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Genetics
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Origin : Publication funded by an institution
Licence : CC BY NC ND - Attribution - NonCommercial - NoDerivatives

Dates and versions

hal-04268667 , version 1 (02-11-2023)

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Attribution - NonCommercial - NoDerivatives

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Hassan Saei, Vincent Morinière, Laurence Heidet, Olivier Gribouval, Said Lebbah, et al.. VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease. iScience, 2023, 26 (7), pp.107171. ⟨10.1016/j.isci.2023.107171⟩. ⟨hal-04268667⟩
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