The Structure of Haplotype Blocks in the Human Genome Stacey

(n ! 2). In all cases, histological examination indicated normal spermatogenesis. We analyzed karyotypes and conducted STS-based assays for Yq microdeletions on eight individuals and detected no abnormalities. Seminiferous tubules were prepared for immunolocalization and fluorescence in situ hybridization (FISH) as described (5). We conducted standard immunostaining (23) with CREST antiserum to detect kinetochores and antibodies against MLH1 and either of two SC proteins, SCP1 and SCP3. Pachytene cells were identified on a Zeiss epifluorescencemicroscope, and images were captured with an Applied Imaging Quips Pathvision System. For subsequent FISH, we used paint probes ( Vysis) to identify chromosomes 1, 16, 21, and 22. Cells with previously captured images were relocated on the microscope, and new images were captured. We attempted to analyze 50 cells per individual, scoring the number of MLH1 foci per autosomal bivalent and the total number of foci per autosomal complement. The XY bivalent was excluded, as it desynapses before the autosomes. In virtually all cells analyzed, at least one MLH1 focus was present on each autosome. Thus, special mechanisms to segregate achiasmate chromosomes, a feature of meiosis in organisms such as Drosophila (24), are unlikely to be an important component of human male meiosis. 7. D. A. Laurie, M. A. Hulten, Ann. Hum. Genet. 49, 189 (1985). 8. J. Yu et al., Am. J. Hum. Genet. 59, 1186 (1996). 9. B. F. J. Manly, Randomization, Bootstrap and Monte Carlo Methods in Biology (Chapman and Hall/CRC, New York, 1997). 10. M. Hattori et al., Nature 405, 311 (2000). 11. I. Dunham et al., Nature 402, 489 (1999). 12. A. Lynn, C. Kashuk, A. Chakravarti, unpublished data. 13. N. E. Morton, Proc. Natl. Acad. Sci. U.S.A. 88, 7474 (1991). 14. MicroMeasure 3.3 (25) was used to measure SC lengths of individual chromosomes. Because of cellcell variation, we compared only SCs measured in the same cell. SCs were considered equal if their lengths (in micrometers) were within 10% of each other; they were considered unequal if the difference exceeded 10%. For SCs of chromosomes 21 and 22, 22 " 21 in 50 cells and 21 " 22 in 1 cell. For SCs of chromosomes 16 and 19, 16 " 19 in 9 cells, 16 ! 19 in 35 cells, and 19 " 16 in 8 cells. 15. K. E. Koehler, J. P. Cherry, A. Lynn, P. A. Hunt, T. J. Hassold, unpublished data. 16. S. Stack, J. Cell Sci. 71, 159 (1984). 17. M. Sym, G. S. Roeder, Cell 79, 283 (1994). 18. S. L. Page, R. S. Hawley, Genes Dev. 15, 3130 (2001). 19. A. T. C. Carpenter, in Genetic Recombination, R. Kucherlapati, G. R. Smith, Eds. (American Society for Microbiology, Washington, DC, 1988), pp. 529–548. 20. S. Agarwal, G. S. Roeder, Cell 102, 245 (2000). 21. S. K. Mahadevaiah et al., Nature Genet. 27, 271 (2001). 22. C. Tease et al., Am. J. Hum. Genet., in press. 23. L. M. Woods et al., J. Cell Biol. 145, 1395 (1999). 24. R. S. Hawley, W. E. Theurkauf, Trends Genet. 9, 310 (1993). 25. A. Reeves, J. Tear, MicroMeasure for Windows, version 3.3. (2000). http://www.colostate.edu/Depts/ Biology/MicroMeasure. 26. A. Solari, Chromosoma 81, 315 (1980). 27. We thank T. Ashley, H. Willard, and G. Matera for helpful suggestions. This work was funded by National Institutes of Health (NIH) grants HD21341 (to T.J.H.) and HD37502 (to P.A.H.). A.L. is supported by NIH training grant HD07518, and K.E.K. is supported by an American Cancer Society fellowship.