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Updated: Jun 29, 2025

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
Published on: January 9, 2020
Functional associations of evolutionarily recent human genes exhibit sensitivity to the 3D genome landscape and
Katherine Fleck1,2, Victor Luria3,4,5,6, Nitanta Garag1
1Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
Abstract:
Genome organization is intricately tied to regulating genes and associated cell fate decisions. Here, we examine the positioning and functional significance of human genes, grouped by their lineage restriction level, within the 3D organization of the genome. We reveal that genes of different lineage restriction levels have distinct positioning relationships with both domains and loop anchors, and remarkably consistent relationships with boundaries across cell types. While the functional associations of each group of genes are primarily cell type-specific, associations of conserved genes maintain greater stability across 3D genomic features and disease than recently evolved genes. Furthermore, the expression of these genes across various tissues follows an evolutionary progression, such that RNA levels increase from young lineage restricted genes to ancient genes present in most species. Thus, the distinct relationships of gene evolutionary age, function, and positioning within 3D genomic features contribute to tissue-specific gene regulation in development and disease.
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