Genomic Architecture and Disease Implications of Human Chromosome 11: From β-Globin Regulation to 11q13 Oncogenic Amplification and use Meta-Analysis
Abstract
Sonu Kumar, Krishna Singh Pal, Sourabh Kosey and Madhaw Dwivedi
Aim-To comprehensively characterise the structural, epigenetic, and functional genomic landscape of chromosome 11 and to elucidate its role in the pathogenesis of imprinting disorders, malignancies, neuropsychiatric conditions, metabolic dysregulation
Objectives:1.To investigate imprinting control mechanisms at chromosome 11p15 and their contribution to disorders such as Beckwith–Wiedemann syndrome (BWS) and Silver–Russell syndrome (SRS). 2.To evaluate oncogenic amplification events at 11q13, particularly involving CCND1, and their role in tumorigenesis via cell-cycle dysregulation. 3.To analyze linkage disequilibrium-resolved variants in neuropsychiatric loci (DRD2, NCAM1, GRIK4) and their impact on neurotransmission pathways. 4.To examine coding and epigenetic alterations in metabolic genes (INS, KCNQ1, IGF2/H19) associated with diabetes and congenital hyperinsulinism.
Results: Integrative genomic analyses demonstrated that chromosome 11 exhibits extensive heterogeneity, encompassing imprinting domains, oncogenic loci, metabolic regulators, and neuropsychiatric susceptibility regions. Aberrant methylation at 11p15 underlies imprinting disorders such as BWS and SRS. Amplification of 11q13, particularly involving CCND1, promotes tumorigenesis via G1–S cell-cycle progression. Functional variants in neuropsychiatric genes disrupt dopaminergic and glutamatergic signaling, influencing synaptic plasticity. Metabolic gene perturbations impair β-cell function, contributing to diabetes and hyperinsulinism. Long-read sequencing with haplotype phasing enhances the detection of pathogenic variants in the HBB locus, improving diagnostic accuracy for β-thalassemia and sickle-cell disease.