Hassold, T. & Hunt, P. To err (meiotically) is human: the genesis of human aneuploidy. Nat. Rev. Genet. 2, 280–291 (2001).
Gruhn, J. R. & Hoffmann, E. R. Errors of the egg: the establishment and progression of human aneuploidy research in the maternal germline. Annu. Rev. Genet. 56, 369–390 (2022).
Baudat, F., Imai, Y. & de Massy, B. Meiotic recombination in mammals: localization and regulation. Nat. Rev. Genet. 14, 794–806 (2013).
Hassold, T. J. & Hunt, P. A. Missed connections: recombination and human aneuploidy. Prenat. Diagn. 41, 584–590 (2021).
Macklon, N. S., Geraedts, J. P. M. & Fauser, B. C. J. M. Conception to ongoing pregnancy: the ‘black box’ of early pregnancy loss. Hum. Reprod. Update 8, 333–343 (2002).
McCoy, R. C. et al. Meiotic and mitotic aneuploidies drive arrest of in vitro fertilized human preimplantation embryos. Genome Med. 15, 77 (2023).
Handel, M. A. & Schimenti, J. C. Genetics of mammalian meiosis: regulation, dynamics and impact on fertility. Nat. Rev. Genet. 11, 124–136 (2010).
Revenkova, E., Herrmann, K., Adelfalk, C. & Jessberger, R. Oocyte cohesin expression restricted to predictyate stages provides full fertility and prevents aneuploidy. Curr. Biol. 20, 1529–1533 (2010).
Tachibana-Konwalski, K. et al. Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes. Genes Dev. 24, 2505–2516 (2010).
Hassold, T. et al. Failure to recombine is a common feature of human oogenesis. Am. J. Hum. Genet. 108, 16–24 (2021).
Lamb, N. E. et al. Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21. Hum. Mol. Genet. 6, 1391–1399 (1997).
Lister, L. M. et al. Age-related meiotic segregation errors in mammalian oocytes are preceded by depletion of cohesin and Sgo2. Curr. Biol. 20, 1511–1521 (2010).
Gruhn, J. R. et al. Chromosome errors in human eggs shape natural fertility over reproductive life span. Science 365, 1466–1469 (2019).
Halldorsson, B. V. et al. Characterizing mutagenic effects of recombination through a sequence-level genetic map. Science 363, eaau1043 (2019).
Kong, A. et al. Recombination rate and reproductive success in humans. Nat. Genet. 36, 1203–1206 (2004).
Ottolini, C. S. et al. Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates. Nat. Genet. 47, 727–735 (2015).
Bell, A. D. et al. Insights into variation in meiosis from 31,228 human sperm genomes. Nature 583, 259–264 (2020).
Hinch, A. G. et al. Factors influencing meiotic recombination revealed by whole-genome sequencing of single sperm. Science 363, eaau8861 (2019).
McCoy, R. C. et al. Evidence of selection against complex mitotic-origin aneuploidy during preimplantation development. PLoS Genet. 11, e1005601 (2015).
Warren, A. C. et al. Evidence for reduced recombination on the nondisjoined chromosomes 21 in Down syndrome. Science 237, 652–654 (1987).
Lamb, N. E. et al. Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II. Nat. Genet. 14, 400–405 (1996).
Ariad, D. et al. Aberrant landscapes of maternal meiotic crossovers contribute to aneuploidies in human embryos. Genome Res. 34, 70–84 (2024).
Coop, G., Wen, X., Ober, C., Pritchard, J. K. & Przeworski, M. High-resolution mapping of crossovers reveals extensive variation in fine-scale recombination patterns among humans. Science 319, 1395–1398 (2008).
Porubsky, D. et al. Human de novo mutation rates from a four-generation pedigree reference. Nature 643, 427–436 (2025).
Kong, A. et al. Common and low-frequency variants associated with genome-wide recombination rate. Nat. Genet. 46, 11–16 (2014).
GTEx Consortium The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369, 1318–1330 (2020).
Gómez-H, L. et al. C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility. Nat. Commun. 7, 13298 (2016).
Strong, E. R. & Schimenti, J. C. Evidence implicating CCNB1IP1, a RING domain-containing protein required for meiotic crossing over in mice, as an E3 SUMO ligase. Genes 1, 440–451 (2010).
Wang, S. et al. Per-nucleus crossover covariation and implications for evolution. Cell 177, 326–338 (2019).
Hassold, T. J. A cytogenetic study of repeated spontaneous abortions. Am. J. Hum. Genet. 32, 723–730 (1980).
Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434–443 (2020).
Revenkova, E. et al. Cohesin SMC1 beta is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination. Nat. Cell Biol. 6, 555–562 (2004).
Murdoch, B. et al. Altered cohesin gene dosage affects mammalian meiotic chromosome structure and behavior. PLoS Genet. 9, e1003241 (2013).
Taylor, D. J. et al. Sources of gene expression variation in a globally diverse human cohort. Nature 632, 122–130 (2024).
Garcia-Alonso, L. et al. Single-cell roadmap of human gonadal development. Nature 607, 540–547 (2022).
Roadmap Epigenomics Consortium et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317–330 (2015).
Chitiashvili, T. et al. Female human primordial germ cells display X-chromosome dosage compensation despite the absence of X-inactivation. Nat. Cell Biol. 22, 1436–1446 (2020).
ENCODE Project Consortium An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).
Xiong, M. et al. A common variant rs2272804 in the 5′UTR of RIBC2 inhibits downstream gene expression by creating an upstream open reading frame. Eur. Rev. Med. Pharmacol. Sci. 24, 3839–3848 (2020).
Fan, S. et al. Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans. Am. J. Hum. Genet. 108, 324–336 (2021).
Sánchez-Sáez, F. et al. Meiotic chromosome synapsis depends on multivalent SYCE1–SIX6OS1 interactions that are disrupted in cases of human infertility. Sci. Adv. 6, eabb1660 (2020).
Schmiesing, J. A., Gregson, H. C., Zhou, S. & Yokomori, K. A human condensin complex containing hCAP-C-hCAP-E and CNAP1, a homolog of Xenopus XCAP-D2, colocalizes with phosphorylated histone H3 during the early stage of mitotic chromosome condensation. Mol. Cell. Biol. 20, 6996–7006 (2000).
Ruth, K. S. et al. Genetic insights into biological mechanisms governing human ovarian ageing. Nature 596, 393–397 (2021).
Kentistou, K. A. et al. Understanding the genetic complexity of puberty timing across the allele frequency spectrum. Nat. Genet. 56, 1397–1411 (2024).
Reynolds, A. et al. RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis. Nat. Genet. 45, 269–278 (2013).
Day, F. R. et al. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nat. Genet. 47, 1294–1303 (2015).
Stankovic, S. et al. Genetic links between ovarian ageing, cancer risk and de novo mutation rates. Nature 633, 608–614 (2024).
Venkatesh, S. S. et al. Genome-wide analyses identify 21 infertility loci and relationships with reproductive traits across the allele frequency spectrum. Nat. Genet. 57, 1107–1118 (2025).
Albers, P. K. & McVean, G. Dating genomic variants and shared ancestry in population-scale sequencing data. PLoS Biol. 18, e3000586 (2020).
Lawson, D. W. & Mace, R. Parental investment and the optimization of human family size. Philos. Trans. R. Soc. Lond. B Biol. Sci. 366, 333–343 (2011).
Mathieson, I. et al. Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus. Nat. Hum. Behav. 7, 790–801 (2023).
Lande, R. & Arnold, S. J. The measurement of selection on correlated characters. Evolution 37, 1210–1226 (1983).
Zhou, D., Zhou, Y., Xu, Y., Meng, R. & Gamazon, E. R. A phenome-wide scan reveals convergence of common and rare variant associations. Genome Med. 15, 101 (2023).
Hou, D. et al. Variations of C14ORF39 and SYCE1 identified in idiopathic premature ovarian insufficiency and nonobstructive azoospermia. J. Clin. Endocrinol. Metab. 107, 724–734 (2022).
Mastrorosa, F. K. et al. Complete chromosome 21 centromere sequences from a Down syndrome family reveal size asymmetry and differences in kinetochore attachment. Preprint at bioRxiv https://doi.org/10.1101/2024.02.25.581464 (2025).
Hinch, R., Donnelly, P. & Hinch, A. G. Meiotic DNA breaks drive multifaceted mutagenesis in the human germ line. Science 382, eadh2531 (2023).
Forni, D., Mozzi, A., Sironi, M. & Cagliani, R. Positive selection drives the evolution of the structural maintenance of chromosomes (SMC) complexes. Genes 15, 1159 (2024).
Biddanda, A., Carioscia, S., Starostik, M. & McCoy, R. Data for ‘Carioscia, S. A., Biddanda, A., et al. (2025). Common variation in meiosis genes shapes human recombination phenotypes and aneuploidy risk’. Zenodo https://doi.org/10.5281/zenodo.15114527 (2025).
Biddanda, A. mccoy-lab/natera_genotyping: final submission. Zenodo https://doi.org/10.5281/zenodo.17429676 (2025).
Biddanda, A. & McCoy, R. mccoy-lab/natera_recomb: final submission. Zenodo https://doi.org/10.5281/zenodo.17429678 (2025).
Biddanda, A. mccoy-lab/karyohmm: final submission. Zenodo https://doi.org/10.5281/zenodo.17429669 (2025).
Carioscia, S., Biddanda, A. & Starostik, M. mccoy-lab/natera_aneuploidy: final submission. Zenodo https://doi.org/10.5281/zenodo.17429672 (2025).
