Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage.

ABSTRACT: Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unann

SUBMITTER: Chen Z 

PROVIDER: S-EPMC8024253 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature