Targeted Locus Amplification and Haplotyping.

Cystic fibrosis Genetic variation Haplotyping Next generation sequencing Organoids Phasing Proximity ligation Targeted Locus Amplification (TLA)

Journal

Methods in molecular biology (Clifton, N.J.)
ISSN: 1940-6029
Titre abrégé: Methods Mol Biol
Pays: United States
ID NLM: 9214969

Informations de publication

Date de publication:
2023
Historique:
entrez: 6 11 2022
pubmed: 7 11 2022
medline: 9 11 2022
Statut: ppublish

Résumé

Targeted locus amplification (TLA) allows for the detection of all genetic variation (including structural variation) in a genomic region of interest. As TLA is based on proximity ligation, variants can be linked to each other, thereby enabling allelic phasing and the generation of haplotypes. This allows for the study of genetic variants in an allele-specific manner. Here, we provide a step-by-step protocol for TLA sample preparation and a complete bioinformatics pipeline for the allelic phasing of TLA data. Additionally, to illustrate the protocol, we show the ability of TLA to re-sequence and haplotype the complete cystic fibrosis transmembrane (CFTR) gene (> 200 kb in size) from patient-derived intestinal organoids.

Identifiants

pubmed: 36335490
doi: 10.1007/978-1-0716-2819-5_2
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

31-48

Informations de copyright

© 2023. The Author(s).

Références

De Vree PJP, De Wit E, Yilmaz M et al (2014) Targeted sequencing by proximity ligation for comprehensive variant detection and local haplotyping. Nat Biotechnol 32:1019–1025. https://doi.org/10.1038/nbt.2959
doi: 10.1038/nbt.2959 pubmed: 25129690
Snyder MW, Adey A, Kitzman JO, Shendure J (2015) Haplotype-resolved genome sequencing: experimental methods and applications. Nat Rev Genet 16:344–358. https://doi.org/10.1038/nrg3903
doi: 10.1038/nrg3903 pubmed: 25948246
Hottentot QP, Van MM, Splinter E, White SJ (2017) Targeted locus Amplifi cation and next-generation sequencing. Methods Mol Biol 1492:185–196. https://doi.org/10.1007/978-1-4939-6442-0
doi: 10.1007/978-1-4939-6442-0 pubmed: 27822865
Dekkers JF, Berkers G, Kruisselbrink E et al (2016) Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis. Sci Transl Med 8:1–12. https://doi.org/10.1126/scitranslmed.aad8278
doi: 10.1126/scitranslmed.aad8278
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Auteurs

Juliet W Lefferts (JW)

Department of Pediatric Respiratory Medicine, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
Regenerative Medicine Center, Center for Living Technologies, University Medical Center Utrecht, Utrecht, The Netherlands.

Vera Boersma (V)

Cergentis BV, Utrecht, The Netherlands.

Marne C Hagemeijer (MC)

Department of Pediatric Respiratory Medicine, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
Regenerative Medicine Center, Center for Living Technologies, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.

Karima Hajo (K)

Cergentis BV, Utrecht, The Netherlands.

Jeffrey M Beekman (JM)

Department of Pediatric Respiratory Medicine, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
Regenerative Medicine Center, Center for Living Technologies, University Medical Center Utrecht, Utrecht, The Netherlands.

Erik Splinter (E)

Cergentis BV, Utrecht, The Netherlands. erik.splinter@cergentis.com.

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