Universität zu Köln

Wenzel, Andrea, Altmueller, Janine, Ekici, Arif B., Popp, Bernt ORCID: 0000-0002-3679-1081, Stueber, Kurt, Thiele, Holger, Pannes, Alois, Staubach, Simon, Salido, Eduardo ORCID: 0000-0001-9599-9854, Nuernberg, Peter, Reinhardt, Richard ORCID: 0000-0001-9376-2132, Reis, Andre ORCID: 0000-0002-6301-6363, Rump, Patrick, Hanisch, Franz-Georg, Wolf, Matthias T. F., Wiesener, Michael, Huettel, Bruno and Beck, Bodo B. (2018). Single molecule real time sequencing in ADTKD-MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations. Sci Rep, 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Recently, the Mucin-1 (MUC1) gene has been identified as a causal gene of autosomal dominant tubulointerstitial kidney disease (ADTKD). Most causative mutations are buried within a GC-rich 60 basepair variable number of tandem repeat (VNTR), which escapes identification by massive parallel sequencing methods due to the complexity of the VNTR. We established long read single molecule real time sequencing (SMRT) targeted to the MUC1-VNTR as an alternative strategy to the snapshot assay. Our approach allows complete VNTR assembly, thereby enabling the detection of all variants residing within the VNTR and simultaneous determination of VNTR length. We present high resolution data on the VNTR architecture for a cohort of snapshot positive (n = 9) and negative (n = 7) ADTKD families. By SMRT sequencing we could confirm the diagnosis in all previously tested cases, reconstruct both VNTR alleles and determine the exact position of the causative variant in eight of nine families. This study demonstrates that precise positioning of the causative mutation(s) and identification of other coding and noncoding sequence variants in ADTKD-MUC1 is feasible. SMRT sequencing could provide a powerful tool to uncover potential factors encoded within the VNTR that associate with intra-and interfamilial phenotype variability of MUC1 related kidney disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wenzel, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Ekici, Arif B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Popp, Bernt UNSPECIFIED orcid.org/0000-0002-3679-1081 UNSPECIFIED Stueber, Kurt UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Pannes, Alois UNSPECIFIED UNSPECIFIED UNSPECIFIED Staubach, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Salido, Eduardo UNSPECIFIED orcid.org/0000-0001-9599-9854 UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, Richard UNSPECIFIED orcid.org/0000-0001-9376-2132 UNSPECIFIED Reis, Andre UNSPECIFIED orcid.org/0000-0002-6301-6363 UNSPECIFIED Rump, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Hanisch, Franz-Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Matthias T. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesener, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Huettel, Bruno UNSPECIFIED UNSPECIFIED UNSPECIFIED Beck, Bodo B. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-192921
DOI:	10.1038/s41598-018-22428-0
Journal or Publication Title:	Sci Rep
Volume:	8
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUC1 GENE; KIDNEY; DIAGNOSIS; CHROMOSOME-1; NEPHROPATHY; EXPRESSION; MANAGEMENT; DNA Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19292