A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

Mosaic deletion patterns of the human antibody heavy chain gene locus shown by Bayesian haplotyping




TekijätGidoni M, Snir O, Peres A, Polak P, Lindeman I, Mikocziova I, Sarna VK, Lundin KEA, Clouser C, Vigneault F, Collins AM, Sollid LM, Yaari G

KustantajaNATURE PUBLISHING GROUP

Julkaisuvuosi2019

JournalNature Communications

Tietokannassa oleva lehden nimiNATURE COMMUNICATIONS

Lehden akronyymiNAT COMMUN

Artikkelin numeroARTN 628

Vuosikerta10

Sivujen määrä14

ISSN2041-1723

DOIhttps://doi.org/10.1038/s41467-019-08489-3

Verkko-osoitehttps://www.nature.com/articles/s41467-019-08489-3


Tiivistelmä
Analysis of antibody repertoires by high-throughput sequencing is of major importance in understanding adaptive immune responses. Our knowledge of variations in the genomic loci encoding immunoglobulin genes is incomplete, resulting in conflicting VDJ gene assignments and biased genotype and haplotype inference. Haplotypes can be inferred using IGHJ6 heterozygosity, observed in one third of the people. Here, we propose a robust novel method for determining VDJ haplotypes by adapting a Bayesian framework. Our method extends haplotype inference to IGHD- and IGHV-based analysis, enabling inference of deletions and copy number variations in the entire population. To test this method, we generated a multi-individual data set of naive B-cell repertoires, and found allele usage bias, as well as a mosaic, tiled pattern of deleted IGHD and IGHV genes. The inferred haplotypes may have clinical implications for genetic disease predispositions. Our findings expand the knowledge that can be extracted from antibody repertoire sequencing data.



Last updated on 2024-26-11 at 11:59