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Extreme enrichment of VNTR-associated polymorphicity in human subtelomeres: genes with most VNTRs are predominantly expressed in the brain.

التفاصيل البيبلوغرافية
العنوان: Extreme enrichment of VNTR-associated polymorphicity in human subtelomeres: genes with most VNTRs are predominantly expressed in the brain.
المؤلفون: Linthorst J; Department of Clinical Genetics, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands., Meert W; Department of Human Genetics, KU Leuven, Leuven, Belgium., Hestand MS; Department of Human Genetics, KU Leuven, Leuven, Belgium., Korlach J; Pacific Biosciences, Menlo Park, CA, USA., Vermeesch JR; Department of Human Genetics, KU Leuven, Leuven, Belgium., Reinders MJT; Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands., Holstege H; Department of Clinical Genetics, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands. h.holstege@amsterdamumc.nl.; Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands. h.holstege@amsterdamumc.nl.; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands. h.holstege@amsterdamumc.nl.
المصدر: Translational psychiatry [Transl Psychiatry] 2020 Nov 02; Vol. 10 (1), pp. 369. Date of Electronic Publication: 2020 Nov 02.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101562664 Publication Model: Electronic Cited Medium: Internet ISSN: 2158-3188 (Electronic) Linking ISSN: 21583188 NLM ISO Abbreviation: Transl Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature Pub. Group
مواضيع طبية MeSH: Genome, Human* , Minisatellite Repeats*/genetics, Aged, 80 and over ; Brain ; Female ; Haplotypes ; Humans ; Sequence Analysis, DNA
مستخلص: The human genome harbors numerous structural variants (SVs) which, due to their repetitive nature, are currently underexplored in short-read whole-genome sequencing approaches. Using single-molecule, real-time (SMRT) long-read sequencing technology in combination with FALCON-Unzip, we generated a de novo assembly of the diploid genome of a 115-year-old Dutch cognitively healthy woman. We combined this assembly with two previously published haploid assemblies (CHM1 and CHM13) and the GRCh38 reference genome to create a compendium of SVs that occur across five independent human haplotypes using the graph-based multi-genome aligner REVEAL. Across these five haplotypes, we detected 31,680 euchromatic SVs (>50 bp). Of these, ~62% were comprised of repetitive sequences with 'variable number tandem repeats' (VNTRs), ~10% were mobile elements (Alu, L1, and SVA), while the remaining variants were inversions and indels. We observed that VNTRs with GC-content >60% and repeat patterns longer than 15 bp were 21-fold enriched in the subtelomeric regions (within 5 Mb of the ends of chromosome arms). VNTR lengths can expand to exceed a critical length which is associated with impaired gene transcription. The genes that contained most VNTRs, of which PTPRN2 and DLGAP2 are the most prominent examples, were found to be predominantly expressed in the brain and associated with a wide variety of neurological disorders. Repeat-induced variation represents a sizeable fraction of the genetic variation in human genomes and should be included in investigations of genetic factors associated with phenotypic traits, specifically those associated with neurological disorders. We make available the long and short-read sequence data of the supercentenarian genome, and a compendium of SVs as identified across 5 human haplotypes.
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معلومات مُعتمدة: N/A International Stichting Dioraphte (Dioraphte Foundation); WE09.2014-03 International Alzheimer Nederland (Alzheimer Netherlands)
تواريخ الأحداث: Date Created: 20201103 Date Completed: 20210618 Latest Revision: 20210618
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7608644
DOI: 10.1038/s41398-020-01060-5
PMID: 33139705
قاعدة البيانات: MEDLINE
الوصف
تدمد:2158-3188
DOI:10.1038/s41398-020-01060-5