Recurrent DNA inversion rearrangements in the human genome
- Margarita Flores*,
- Lucía Morales*,
- Claudia Gonzaga-Jauregui*,
- Rocío Domínguez-Vidaña*,
- Cinthya Zepeda*,
- Omar Yañez*,
- María Gutiérrez*,
- Tzitziki Lemus*,
- David Valle*,
- Ma. Carmen Avila*,
- Daniel Blanco*,
- Sofía Medina-Ruiz*,
- Karla Meza*,
- Erandi Ayala*,
- Delfino García*,
- Patricia Bustos*,
- Víctor González*,
- Lourdes Girard*,
- Teresa Tusie-Luna†,‡,
- Guillermo Dávila*, and
- Rafael Palacios*,§
- *Centro de Ciencias Genómicas and
- †Unidad de Biología Molecular y Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, 62210, Mexico; and
- ‡Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, 14000, Mexico D.F., Mexico
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Contributed by Rafael Palacios, February 22, 2007 (received for review January 18, 2007)
Abstract
Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome. In particular, we have identified intrachromosomal identical repeats that are located in reverse orientation, which may lead to chromosomal inversions. A bioinformatic workflow pathway to select appropriate regions for analysis was developed. Three such regions overlapping with known human genes, located on chromosomes 3, 15, and 19, were analyzed. The relative proportion of wild-type to rearranged structures was determined in DNA samples from blood obtained from different, unrelated individuals. The results obtained indicate that recurrent genomic rearrangements occur at relatively high frequency in somatic cells. Interestingly, the rearrangements studied were significantly more abundant in adults than in newborn individuals, suggesting that such DNA rearrangements might start to appear during embryogenesis or fetal life and continue to accumulate after birth. The relevance of our results in regard to human genomic variation is discussed.
Footnotes
- §To whom correspondence should be addressed at: Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México. Av. Universidad s/n, Col. Chamilpa, Cuernavaca, Morelos, 62210, México. E-mail: palacios{at}ccg.unam.mx
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This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected on April 25, 2006.
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Author contributions: M.F., L.M., C.G.-J., R.D.-V., and R.P. designed research; M.F. performed research; L.M., C.G.-J., R.D.-V., C.Z., O.Y., M.G., T.L., D.V., M.C.A., D.B., S.M.-R., K.M., E.A., D.G., P.B., V.G., L.G., T.T.-L., and G.D. contributed new reagents/analytic tools; M.F., L.M., C.G.-J., R.D.-V., C.Z., O.Y., and D.G. analyzed data; and L.M., C.G.-J., R.D.-V., and R.P. wrote the paper.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0701631104/DC1.
- Abbreviations:
- IR-n,
- inverted region n;
- NAHR,
- nonallelic homologous recombination;
- PRIS,
- potential recombinogenic inverted sequences;
- RKit,
- rearrangement kit.
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Freely available online through the PNAS open access option.
- © 2007 by The National Academy of Sciences of the USA
