Feature co-localization landscape of the human genome

Abstract

Although feature co-localizations could serve as useful guide-posts to genome architecture, a comprehensive and quantitative feature co-localization map of the human genome has been lacking. Herein we show that, in contrast to the conventional bipartite division of genomic sequences into genic and inter-genic regions, pairwise co-localizations of forty-two genomic features in the twenty-two autosomes based on 50-kb to 2,000-kb sequence windows indicate a tripartite zonal architecture comprising Genic zones enriched with gene-related features and Alu-elements; Proximal zones enriched with MIR- and L2-elements, transcription-factor-binding-sites (TFBSs), and conserved-indels (CIDs); and Distal zones enriched with L1-elements. Co-localizations between single-nucleotide-polymorphisms (SNPs) and copy-number-variations (CNVs) reveal a fraction of sequence windows displaying steeply enhanced levels of SNPs, CNVs and recombination rates that point to active adaptive evolution in such pathways as immune response, sensory perceptions, and cognition. The strongest positive co-localization observed between TFBSs and CIDs suggests a regulatory role of CIDs in cooperation with TFBSs. The positive co-localizations of cancer somatic CNVs (CNVT) with all Proximal zone and most Genic zone features, in contrast to the distinctly more restricted co-localizations exhibited by germline CNVs (CNVG), reveal disparate distributions of CNVTs and CNVGs indicative of dissimilarity in their underlying mechanisms.

Association of ACE <i>DD</i> Genotype with Hypertension among the Tribal Populations of South India

“…ACE gene is one of the insertional polymorphisms of Alu elements [44][45]. Many reports studied the Alu polymorphisms in the context of human genetics and evolution [46][47][48][49][50][51][52][53] . Recently, various studies reported the relationship between ACE gene polymorphism and Type 2 Diabetes.…”

Tripartite genome of all species

“…Ho also stated that although MGD theory solved the paradoxes in molecular evolution, the diversity of complex species at somatic level can’t be explained by it. Our recent study 6 on human genome architecture discovered not only variable but also functional regions of the human genome. In an attempt to provide a more comprehensive view of genome structure and molecular evolution, we developed the IFV hypothesis based on our discovery of the variable property of the gene regulatory region.…”

“…Here we proposed the Increasing Functional Variation (IFV) hypothesis inspired by both the MGD theory 2 and our recent work on human genome architecture 6 . Recently, based on co-localization of various genomic features we divided the human genome into three parts, referred to as gene enriched (Genic) zones, gene regulatory elements enriched (Proximal) zones and non-functional features enriched (Distal) zones 6 . We regard the Genic zones as mainly functional and invariable, and the Distal zones as mainly non-functional and variable.…”

Genomic subtyping of liver cancers with prognostic application

“…Similarly, the experimental AluScan sequences obtained from the 15 Chinese HCC patients as described in Materials and Methods (data S2) defined the AluScan amplifiable sequences in the WGS that covered~2.1% of the genome, and extraction of these sequences from each WGS of the 110 Liver tumor samples yielded the AluScan-subset sequences. In this regard, it may be noted that DNA sequences in the human genome are classified into Genic zones enriched with gene sequences, Proximal zones adjacent to genes and enriched with enhancers, and Distal zones relatively depleted in genes [29]; into different cellcycle phases regarding the timing of DNA duplication; and into exonic regions containing coding sequences (CDS), their adjoining untranslated regions (UTRs), and nonCDS segments on the RNA transcripts. Since the WGS sequence, the Exome-subset sequences and the AluScan-subset sequences differ from one another in terms of (i) the proportions of Genic zones, Proximal zones and Distal zones they contain; (ii) the profile of duplication times of their DNAs in the cell cycle; and (iii) the abundance of exonic regions found in them ( Fig.…”