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  • Print publication year: 2013
  • Online publication date: July 2013

6 - Meiotic recombination in human oocytes

from Part 3 - The embryo/blastomere


This chapter reviews the sexually dimorphic nature of meiosis in mammalian species, since many aspects of recombination depend on whether the gamete is proceeding through spermatogenesis or oogenesis. Since meiotic recombination occurs at prophase during fetal development in mammalian females, few investigations of human recombination have focused on this stage. Linkage disequilibrium (LD) analysis provides a powerful tool for the generation of high resolution genetic maps. LD mapping does not require analysis of multiple generations in a family. Rather it is a simple assessment of haplotype blocks among different individuals. Fortunately, with improvements in immunostaining techniques and the increasing availability of antibodies capable of detecting meiosis-acting proteins, it has now become possible to analyze the processes of pairing, synapsis, and recombination in human fetal oocytes. Advances in mapping methodology have led to the generation of high-resolution male and female genetic maps.


1. Nagaoka, S., Hassold, T., Hunt, P.Human aneuploidy: mechanisms and new insights to an age old problem. Nature Reviews Genetics. 2012; 13(7): 493–504.
2. Baudat, F., de Massy, B.Regulating double-stranded DNA break repair towards crossover or non-crossover during mammalian meiosis. Chromosome Research. 2007; 15(5): 565–577.
3. Longhese, M.P., Bonetti, D., Guerini, I., Manfrini, N., Clerici, M.DNA double-strand breaks in meiosis: checking their formation, processing and repair. DNA Repair (Amsterdam). 2009; 8(9): 1127–1138.
4. Szekvolgyi, L., Nicolas, A.From meiosis to postmeiotic events: homologous recombination is obligatory but flexible. FEBS Journal. 2009; 277(3): 571–589.
5. Lenzi, M.L., Smith, J., Snowden, al. Extreme heterogeneity in the molecular events leading to the establishment of chiasmata during meiosis I in human oocytes. American Journal of Human Genetics. 2005; 76(1): 112–127.
6. Revenkova, E., Eijpe, M., Heyting, al. Cohesin SMC1 beta is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination. Nature Cell Biology. 2004; 6(6): 555–562.
7. Xu, H., Beasley, M.D., Warren, W.D., van der Horst, G.T., McKay, M.J.Absence of mouse REC8 cohesin promotes synapsis of sister chromatids in meiosis. Developmental Cell. 2005; 8(6): 949–961.
8. Yuan, L., Liu, J.G., Hoja, al. Female germ cell aneuploidy and embryo death in mice lacking the meiosis-specific protein SCP3. Science. 2002; 296(5570): 1115–1118.
9. Race, R.R., Sanger, R.Blood Groups in Man, 6th edn. Chichester: Blackwell Science Ltd. 1975.
10. Harris, H.Enzyme polymorphisms in man. Proceedings of the Royal Society of London B, Biological Science. 1966; 164(995): 298–310.
11. Westerveld, A., Jongsma, A.P., Meera Khan, P., van Someren, H., Bootsma, D.Assignment of the AK1: Np: ABO linkage group to human chromosome 9. Proceedings of the National Academy of Sciences of the United States of America. 1976; 73(3): 895–899.
12. Hassold, T., Kumlin, E., Takaesu, N., Leppert, M.Use of restriction fragment length polymorphisms to study the origin of human aneuploidy. Annals of the New York Academy of Science. 1985; 450: 179–189.
13. Jeffreys, A.J., Wilson, V., Thein, S.L.Hypervariable ‘minisatellite’ regions in human DNA. Nature. 1985; 314(6006): 67–73.
14. Weber, J.L. Human DNA polymorphisms and methods of analysis. Current Opinion in Biotechnology. 1990; 1(2): 166–171.
15. Kong, A., Thorleifsson, G., Gudbjartsson, al. Fine-scale recombination rate differences between sexes, populations and individuals. Nature. 2010; 467(7319): 1099–1103.
16. 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. 2008; 319(5868): 1395–1398.
17. Rosenberg, N.A., Huang, L., Jewett, al. Genome-wide association studies in diverse populations. Nature Reviews Genetics. 2010; 11(5): 356–366.
18. Hall, H.E., Chan, E.R., Collins, al. The origin of trisomy 13. American Journal of Medical Genetics A. 2007; 143A(19): 2242–2248.
19. Robinson, W.P., Kuchinka, B.D., Bernasconi, al. Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination. Human Molecular Genetics. 1998; 7(6): 1011–1019.
20. Bugge, M., Collins, A., Hertz, al. Non-disjunction of chromosome 13. Human Molecular Genetics. 2007; 16(16): 2004–2010.
21. Bugge, M., Collins, A., Petersen, al. Non-disjunction of chromosome 18. Human Molecular Genetics. 1998; 7(4): 661–669.
22. Hall, H.E., Surti, U., Hoffner, al. The origin of trisomy 22: evidence for acrocentric chromosome-specific patterns of nondisjunction. American Journal of Medical Genetics A. 2007; 143A(19): 2249–2255.
23. Thomas, N.S., Ennis, S., Sharp, al. Maternal sex chromosome non-disjunction: evidence for X chromosome-specific risk factors. Human Molecular Genetics. 2001; 10(3): 243–250.
24. Hassold, T., Hunt, P.To err (meiotically) is human: the genesis of human aneuploidy. Nature Reviews Genetics. 2001; 2(4): 280–291.
25. Lipkin, S.M., Moens, P.B., Wang, al. Meiotic arrest and aneuploidy in MLH3-deficient mice. Nature Genetics. 2002; 31(4): 385–390.
26. Kan, R., Sun, X., Kolas, al. Comparative analysis of meiotic progression in female mice bearing mutations in genes of the DNA mismatch repair pathway. Biology of Reproduction. 2008; 78(3): 462–471.
27. Lynn, A., Koehler, K.E., Judis, al. Covariation of synaptonemal complex length and mammalian meiotic exchange rates. Science. 2002; 296(5576): 2222–2225.
28. Cheng, E.Y., Hunt, P.A., Naluai-Cecchini, al. Meiotic recombination in human oocytes. PLoS Genetics. 2009; 5(9): e1000661.
29. Laurie, D.A., Hulten, M.A.Further studies on chiasma distribution and interference in the human male. Annals of Human Genetics. 1985; 49(Pt 3): 203–214.
30. Hulten, M., Luciani, J.M., Kirton, V., Devictor-Vuillet, M.The use and limitations of chiasma scoring with reference to human genetic mapping. Cytogenetics and Cell Genetics. 1978; 22(1–6): 37–58.
31. Schuler, G.D., Boguski, M.S., Stewart, al. A gene map of the human genome. Science. 1996; 274(5287): 540–546.
32. Matise, T.C., Chen, F., Chen, al. A second-generation combined linkage physical map of the human genome. Genome Research. 2007; 17(12): 1783–1786.
33. Jorgenson, E., Tang, H., Gadde, al. Ethnicity and human genetic linkage maps. American Journal of Human Genetics. 2005; 76(2): 276–290.
34. Ju, Y.S., Park, H., Lee, al. A genome-wide Asian genetic map and ethnic comparison: the GENDISCAN study. BMC Genomics. 2008; 9: 554.
35. Broman, K.W., Murray, J.C., Sheffield, V.C., White, R.L., Weber, J.L.Comprehensive human genetic maps: individual and sex-specific variation in recombination. American Journal of Human Genetics. 1998; 63(3): 861–869.
36. Hussin, J., Roy-Gagnon, M.H., Gendron, R., Andelfinger, G., Awadalla, P.Age-dependent recombination rates in human pedigrees. PLoS Genetics. 2011; 7(9): e1002251.
37. Cheung, V.G., Burdick, J.T., Hirschmann, D., Morley, M.Polymorphic variation in human meiotic recombination. American Journal of Human Genetics. 2007; 80(3): 526–530.
38. Kong, A., Gudbjartsson, D.F., Sainz, al. A high-resolution recombination map of the human genome. Nature Genetics. 2002; 31(3): 241–247.
39. Kong, X., Murphy, K., Raj, al. A combined linkage-physical map of the human genome. American Journal of Human Genetics. 2004; 75(6): 1143–1148.
40. Henderson, S.A., Edwards, R.G.Chiasma frequency and maternal age in mammals. Nature. 1968; 218(5136): 22–28.
41. Stefansson, H., Helgason, A., Thorleifsson, al. A common inversion under selection in Europeans. Nature Genetics. 2005; 37(2): 129–137.
42. Chowdhury, R., Bois, P.R., Feingold, al. Genetic analysis of variation in human meiotic recombination. PLoS Genetics. 2009; 5(9): e1000648.
43. Fledel-Alon, A., Leffler, E.M., Guan, al. Variation in human recombination rates and its genetic determinants. PLoS One 2011; 6(6): e20321.
44. Kong, A., Thorleifsson, G., Stefansson, al. Sequence variants in the RNF212 gene associate with genome-wide recombination rate. Science. 2008; 319(5868): 1398–1401.
45. Borde, V., Robine, N., Lin, al. Histone H3 lysine 4 trimethylation marks meiotic recombination initiation sites. EMBO Journal. 2009; 28(2): 99–111.
46. Buard, J., Barthes, P., Grey, C., de Massy, B.Distinct histone modifications define initiation and repair of meiotic recombination in the mouse. EMBO Journal. 2009; 28(17): 2616–2624.
47. Hayashi, K., Yoshida, K., Matsui, Y. Ahistone H3 methyltransferase controls epigenetic events required for meiotic prophase. Nature. 2005; 438(7066): 374–378.
48. Hayashi, K., Matsui, Y.Meisetz, a novel histone tri-methyltransferase, regulates meiosis-specific epigenesis. Cell Cycle. 2006; 5(6): 615–620.
49. Barlow, A.L., Hulten, M.A.Combined immunocytogenetic and molecular cytogenetic analysis of meiosis I oocytes from normal human females. Zygote. 1998; 6(1): 27–38.
50. Tease, C., Hartshorne, G.M., Hulten, M.A.Patterns of meiotic recombination in human fetal oocytes. American Journal of Human Genetics. 2002; 70(6): 1469–1479.
51. Robles, P., Roig, I., Garcia, al. Pairing and synapsis in oocytes from female fetuses with euploid and aneuploid chromosome complements. Reproduction. 2007; 133(5): 899–907.
52. Lynn, A., Ashley, T., Hassold, T.Variation in human meiotic recombination. Annual Review of Genomics and Human Genetics. 2004; 5: 317–349.
53. Warren, A.C., Chakravarti, A., Wong, al. Evidence for reduced recombination on the nondisjoined chromosomes 21 in Down syndrome. Science. 1987; 237(4815): 652–654.
54. Peterson, M.B., Frantzen, M., Antonarakis, al. Comparative study of microsatellite and cytogenetic markers for detecting the origin of the nondisjoined chromosome 21 in Down syndrome. American Journal of Human Genetics. 1992; 51(3): 516–525.
55. Lamb, N.E., Freeman, S.B., Savage-Austin, al. Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II. Nature Genetics. 1996; 14(4): 400–405.
56. Ghosh, S., Bhaumik, P., Ghosh, P., Dey, S.K.Chromosome 21 non-disjunction and Down syndrome birth in an Indian cohort: analysis of incidence and aetiology from family linkage data. Genetic Research (Cambridge). 2010; 92(3): 189–197.
57. Lamb, N.E., Feingold, E., Savage, al. Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21. Human Molecuar Genetics. 1997; 6(9): 1391–1399.
58. Oliver, T.R., Feingold, E., Yu, al. New insights into human nondisjunction of chromosome 21 in oocytes. PLoS Genetics. 2008; 4(3): e1000033.
59. Molnar, M., Parisi, S., Kakihara, al. Characterization of rec7, an early meiotic recombination gene in Schizosaccharomyces pombe. Genetics. 2001; 157(2): 519–532.
60. Roeder, G.S. Meiotic chromosomes: it takes two to tango. Genes and Development. 1997; 11(20): 2600–2621.
61. Sears, D.D., Hegemann, J.H., Hieter, P.Meiotic recombination and segregation of human-derived artificial chromosomes in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America. 1992; 89(12): 5296–5300.
62. Sears, D.D., Hieter, P., Simchen, G.An implanted recombination hot spot stimulates recombination and enhances sister chromatid cohesion of heterologous YACs during yeast meiosis. Genetics. 1994; 138(4): 1055–1065.
63. Koehler, K.E., Boulton, C.L., Collins, al. Spontaneous X chromosome MI and MII nondisjunction events in Drosophila melanogaster oocytes have different recombinational histories. Nature Genetics. 1996; 14(4): 406–414.
64. Rockmill, B., Voelkel-Meimau, K., Roeder, G.S.Centromere-proximal crossovers are associated with precocious separation of sister chromatids during meiosis in Saccharomyces cerevisiae. Genetics. 2006; 174(4): 1745–1754.
65. Barlow, A.L., Hulten, M.A.Crossing over analysis at pachytene in man. European Journal of Human Genetics. 1998; 6(4): 350–358.
66. Matise, T.C., Perlin, M., Chakravarti, A.Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage map. Nature Genetics. 1994; 6(4): 384–390.
67. Matise, T.C., Sachidanandam, R., Clark, al. A 3.9-centimorgan-resolution human single-nucleotide polymorphism linkage map and screening set. American Journal of Human Genetics. 2003; 73(2): 271–284.
68. Hassold, T., Sherman, S., Hunt, P.Counting cross-overs: characterizing meiotic recombination in mammals. Human Molecular Genetics. 2000; 9(16): 2409–2419.