The human immunoglobulin heavy chain constant gene locus is enriched for large complex structural variants and coding polymorphisms that vary in frequency among human populations.

The immunoglobulin heavy chain constant (IGHC) domain of antibodies (Ab) is responsible for effector functions critical to Ab mediated immunity. In humans, this domain is encoded by genes within the IGHC locus, where descriptions of genomic diversity remain incomplete. To address this, we utilized long-read genomic datasets to build a high-quality IGHC haplotype/variant catalog from 105 individuals of diverse ancestry, and developed a high-throughput approach for targeted long-read IGHC locus sequencing and assembly.

Resolving haplotype variation and complex genetic architecture in the human immunoglobulin kappa chain locus in individuals of diverse ancestry.

Immunoglobulins (IGs), critical components of the human immune system, are composed of heavy and light protein chains encoded at three genomic loci. The IG Kappa (IGK) chain locus consists of two large, inverted segmental duplications. The complexity of the IG loci has hindered use of standard high-throughput methods for characterizing genetic variation within these regions.