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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.

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