Genome biology of long non-coding RNAs in humans: A virtual karyotype.

Long non-coding RNAs (lncRNAs) represent a groundbreaking class of RNA molecules that exert regulatory functions with remarkable tissue and cellular specificity. Although the identification of functionally significant lncRNAs is increasing, a comprehensive profiling of their genomic features remains elusive. Here, we present a detailed overview of the distribution of lncRNA genes across human chromosomes and describe key RNA features-what we refer to as a "virtual lncRNA karyotype"-that provide insights into their biosynthesis and function. To achieve this, we leveraged existing human annotation files to construct a statistical genomic portrait of lncRNAs in comparison with protein-coding genes (PCGs). We found that lncRNAs are unevenly distributed across chromosomes and identified regions of high lncRNA density on chromosomes 18, 13, and X, which overlap with PCG-rich regions. Additionally, we observed that lncRNAs generally exhibit shorter gene lengths and fewer splicing variants compared to protein-coding transcripts, with a subset displaying pronounced clustering patterns that may indicate functional relevance. Finally, we identified several clinically associated and experimentally validated SNPs impacting lncRNA genes (lncGs). Overall, this study provides a foundational reference for exploring the non-coding genome, offering new insights into the genomic characteristics of lncRNAs. These findings may enhance our understanding of their biological significance and potential roles in disease.