Abstract
Several large-scale studies of human genetic variation have provided insights into processes such as recombination that have shaped human diversity. However, regions such as low-copy repeats (LCRs) have proven difficult to characterize, hindering efforts to understand the processes operating in these regions. We present a detailed study of genetic variation and underlying recombination processes in two copies of an LCR (NF1REPa and NF1REPc) on chromosome 17 involved in the generation of NF1 microdeletions and in a third copy (REP19) on chromosome 19 from which the others originated over 6.7 million years ago. We find evidence for shared hotspots of recombination among the LCRs. REP19 seems to contain hotspots in the same place as the nonallelic recombination hotspots in NF1REPa and NF1REPc. This apparent conservation of patterns of recombination hotspots in moderately diverged paralogous regions contrasts with recent evidence that these patterns are not conserved in less-diverged orthologous regions of chimpanzees.
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Acknowledgements
The authors thank T. de Ravel for critically reading the manuscript. T.D. is supported by the Emmanuel Vanderschueren Fonds. M.S. is supported by US National Institutes of Health grant 1RO1HG/LM02585-01. E.L. is a part-time clinical researcher of the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO). This work is also supported by research grants from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (G.0096.02, E.L.; G.0507.04, P.M.); the Interuniversity Attraction Poles (IAP) granted by the Federal Office for Scientific, Technical and Cultural Affairs, Belgium (2002-2006; P5/25) (P.M. and E.L.); by a Concerted Action Grant from the Catholic University of Leuven and by the Belgian Federation against Cancer (SCIE2003-33 to E.L.).
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This study was coordinated by T.D., P.M. and E.L.; the manuscript was written by T.D., M.S. and E.L.; breakpoint detection was performed by T.D., I.H., H.B., L.M., K.S., C.L., K.W., H.K., D.V. and L.K.; SNP detection and typing was performed by T.D., I.H., H.B. and D.T. and computational analysis was performed by T.D. and M.S.
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Supplementary information
Supplementary Fig. 1
Schematic overview of the NF1 microdeletion region. (PDF 492 kb)
Supplementary Fig. 2
LD pattern of the different LCRs. (PDF 416 kb)
Supplementary Fig. 3
Distribution and ratio of lambda values in the LCRs. (PDF 427 kb)
Supplementary Fig. 4
Breakpoint detection. (PDF 548 kb)
Supplementary Table 1
dbSNP numbers (ss) of SNPs used in shared SNP study. (PDF 72 kb)
Supplementary Table 2
SNPs used in the genotyping of 43 nuclear families (PDF 76 kb)
Supplementary Table 3
Primer list. (PDF 903 kb)
Supplementary Table 4
Haplotype and input data. (XLS 123 kb)
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Raedt, T., Stephens, M., Heyns, I. et al. Conservation of hotspots for recombination in low-copy repeats associated with the NF1 microdeletion. Nat Genet 38, 1419–1423 (2006). https://doi.org/10.1038/ng1920
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DOI: https://doi.org/10.1038/ng1920
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