Genotyping of canine MHC gene DLA-88 by next-generation sequencing reveals high frequencies of new allele discovery and gene duplication.


Journal

HLA
ISSN: 2059-2310
Titre abrégé: HLA
Pays: England
ID NLM: 101675570

Informations de publication

Date de publication:
11 2022
Historique:
revised: 12 07 2022
received: 31 03 2022
accepted: 31 07 2022
entrez: 13 10 2022
pubmed: 14 10 2022
medline: 18 10 2022
Statut: ppublish

Résumé

Dogs have served as one of the most reliable preclinical models for a variety of diseases and treatments, including stem/progenitor cell transplantation. At the genetic epicenter of dog transplantation models, polymorphic major histocompatibility complex (MHC) genes are most impactful on transplantation success. Among the canine class I and class II genes, DLA-88 has been best studied in transplantation matching and outcomes, with 129 DLA-88 alleles identified. In this study we developed and tested a next generation (NGS) sequencing protocol for rapid identification of DLA-88 genotypes in dogs and compared the workflow and data generated with an established DLA-88 Sanger sequencing protocol that has been in common prior use for clinical studies. By testing the NGS protocol on a random population of 382 dogs, it was possible to demonstrate superior efficacy based on laboratory execution and overall cost. In addition, NGS proved far more effective at discovering new alleles and detecting multiple alleles associated with gene duplication. A total of 51 new DLA-88 alleles are reported here. This rate of new allele discovery indicates that a large pool of yet un-discovered DLA-88 alleles exists in the domestic dog population. In addition, more than 46% of dogs carried three or more copies of DLA-88, further emphasizing the need for more sensitive and cost-effective DLA typing methodology for the dog clinical model.

Identifiants

pubmed: 36227705
doi: 10.1111/tan.14752
pmc: PMC9563979
mid: NIHMS1827653
doi:

Substances chimiques

Histocompatibility Antigens Class I 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

479-490

Subventions

Organisme : NIDDK NIH HHS
ID : R56 DK117276
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK106829
Pays : United States

Informations de copyright

© 2022 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.

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Auteurs

Chul-Woo Pyo (CW)

Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Scisco Genetics Inc., Seattle, Washington, USA.

Michael A Harkey (MA)

Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington, USA.

Beverly Torok-Storb (B)

Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington, USA.

Rainer Storb (R)

Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Department of Medicine, University of Washington, Seattle, Washington, USA.

Ruihan Wang (R)

Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Scisco Genetics Inc., Seattle, Washington, USA.

Alexander S Thomas (AS)

Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington, USA.

Wyatt C Nelson (WC)

Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Scisco Genetics Inc., Seattle, Washington, USA.

Daniel E Geraghty (DE)

Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Scisco Genetics Inc., Seattle, Washington, USA.

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Classifications MeSH