Plan β solves: integrated cytogenomic mapping reveals hidden structural organization within the human 1q12 non-coding domain

Background Interpretation of variation within the human non-coding genome remains a major challenge, particularly in repetitive regions where genomic diversity arises from differences in higher-order organization rather than nucleotide-level variation alone. The pericentromeric region of chromosome 1 represents one of the most complex domains of the human genome and a key model for studying structural variability within heterochromatic segments. Although cytogenetic variation in 1q12 is consistently observed, its representation in reference genome assemblies remains limited, and its interindividual molecular organization is still incompletely characterized due to sequence alignment limitations. Results Integrated high-resolution cytogenetics and multi-probe fluorescence in situ hybridization mapping targeting α-, β-, and HSat1–3 satellite DNA defined the structural organization of 1q12. Fourteen distinct heterochromatic patterns were identified, with largely preserved euchromatic flanks except for a pericentromeric inversion variant. HSat2/3 signals spanned most of the 1q12 region, whereas negative G- and C-bands consistently corresponded to β-satellite pB4 subdomains, typically found in acrocentric short arms. Conclusions The results demonstrate that cytogenetic banding variation in 1q12 reflects a modular organization of satellite DNA and higher-order repeat architecture rather than uniform heterochromatin expansion and overturn the view of C-bands as uniform markers of constitutive heterochromatin. β-satellite DNA emerges as a previously underappreciated structural component of 1q12, revealing molecular links between chromosome 1 and acrocentric short arms and suggesting a possible evolutionary connection. These findings refine current models of pericentromeric organization and provide new insights into the biological interpretation of structural variation and genomic dynamics within a functionally and clinically relevant non-coding domain.