Structural variation, selection, and diversification of the NPIP gene family from the human pangenome.

ABSTRACT: The NPIP gene family is among the most positively selected gene families in humans/apes and drives independent duplication in primate lineages. These duplications promote genetic instability, leading to recurrent disease-associated microduplication and microdeletion syndromes. Despite its importance, little is known about its function or variation in humans, as short-read sequencing cannot distinguish high-identity duplications. Using long-read assemblies of 169 human haplotypes, we find extreme variation in the content and organization of NPIP loci. We identify fixed and polymorphic paralogs and observe ongoing positive selection. With long-read RNA sequencing (RNA-seq), we create paralog-specific gene models, the majority of which were not previously documented, and observe paralog-speci

SUBMITTER: Dishuck PC 

PROVIDER: S-EPMC12790995 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature