biostudies-literaturede Lima LGNIDA NIH HHSNHGRI NIH HHSNCI NIH HHS952-961https://www.ebi.ac.uk/biostudies/studies/S-EPMC12657243biostudies-literatureUnknown647(8091)Robertsonian chromosomes are a type of variant chromosome that is commonly found in nature. Present in 1 in 800 humans, these chromosomes can underlie infertility, trisomies and increased cancer incidence^1-5. They have been recognized cytogenetically for more than a century⁶, yet their origins have remained unknown. Here we describe complete assemblies of three human Robertsonian chromosomes. We identified a common breakpoint in SST1, a macrosatellite DNA located on chromosomes 13, 14 and 21, which commonly undergo Robertsonian translocation. SST1 is contained within a larger shared homology domain⁷ that is inverted on chromosome 14, which enables a meiotic crossover event that fuses the long arms of two chromosomes. Robertsonian chromosomes have two centroNatureThe formation and propagation of human Robertsonian chromosomes.PMC12657243R01 HG013017U01 DA057530R01 CA266339Hall Kde Lima LGSeidel CCrawford JFagen BLGarrison EYoung ACRhie AWalenz BPBrooks SYPeterson MGuarracino APhillippy AMBouffard GGKoren SPickett BDGerton JLPotapova TMcKinney SSolar SJfalseThe formation and propagation of human Robertsonian chromosomes.Robertsonian chromosomes are a type of variant chromosome that is commonly found in nature. Present in 1 in 800 humans, these chromosomes can underlie infertility, trisomies and increased cancer incidence^1-5. They have been recognized cytogenetically for more than a century⁶, yet their origins have remained unknown. Here we describe complete assemblies of three human Robertsonian chromosomes. We identified a common breakpoint in SST1, a macrosatellite DNA located on chromosomes 13, 14 and 21, which commonly undergo Robertsonian translocation. SST1 is contained within a larger shared homology domain⁷ that is inverted on chromosome 14, which enables a meiotic crossover event that fuses the long arms of two chromosomes. Robertsonian chromosomes have two centro2025-01-01T00:00:00Z2025 Nov2026-06-06T15:44:00.31Z2026-06-02T03:09:15.149ZS-EPMC126572434099338710.1038/s41586-025-09540-8