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A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly
Open accessAbstract
Unequivocal identification of the full composition of a gene is made difficult by the cryptic nature of regulatory elements. Regulatory elements are notoriously difficult to locate and may reside at considerable distances from the transcription units on which they operate and, moreover, may be incorporated into the structure of neighbouring genes. The importance of regulatory mutations as the basis of human abnormalities remains obscure. Here, we show that the chromosome 7q36 associated preaxial polydactyly, a frequently observed congenital limb malformation, results from point mutations in a Shh regulatory element. Shh, normally expressed in the ZPA posteriorly in the limb bud, is expressed in an additional ectopic site at the anterior margin in mouse models of PPD. Our investigations into the basis of the ectopic Shh expression identified the enhancer element that drives normal Shh expression in the ZPA. The regulator, designated ZRS, lies within intron 5 of the Lmbr1 gene 1 Mb from the target gene Shh. The ZRS drives the early spatio-temporal expression pattern in the limb of tetrapods. Despite the morphological differences between limbs and fins, an equivalent regulatory element is found in fish. The ZRS contains point mutations that segregate with polydactyly in four unrelated families with PPD and in the Hx mouse mutant. Thus point mutations residing in long-range regulatory elements are capable of causing congenital abnormalities, and possess the capacity to modify gene activity such that a novel gamut of abnormalities is detected.
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“It soon became clear that enhancers also played vital roles in humans, with non-coding enhancer deletions starting to be linked to severe disease phenotypes such as beta thalassaemia and polydactyly [25–28].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [27]
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“The classic example of this is the Shh ZRS enhancer, which is located within the intron of the Lmbr1 gene approximately 1 megabase distant from Shh [27].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [27]
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“For example, in the mouse genome, the Shh gene and its ZRS (zone of polarizing activity regulatory sequence) enhancer are located about 1 Mb apart [127].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [127]
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“At least a few enhancers reside at great distances from their target gene (e.g. the ZRS enhancer located 1 Mb from the Shh gene118, and a MYC enhancer located 1.7 Mb downstream119), although most are much more proximal to their target promoters72.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [118]
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Cites
Thompson, J. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.24.4876 · Cited by 38,685
A simple salting out procedure for extracting DNA from human nucleated cells
Miller, S. A., Dykes, D. D., & Polesky, H. F. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.3.1215 · Cited by 20,341
Sonic hedgehog mediates the polarizing activity of the ZPA
Riddle, R. D., Johnson, R. L., Laufer, E., & Tabin, C. J. (1993) · Cell · doi:10.1016/0092-8674(93)90626-2 · Cited by 2,285
Echelard, Y., Epstein, D. J., St-Jacques, B., Shen, L., Mohler, J., McMahon, J. A., & McMahon, A. P. (1993) · Cell · doi:10.1016/0092-8674(93)90627-3 · Cited by 2,154
Krauss, S. J. K., Concordet, J., & Ingham, P. W. (1993) · Cell · doi:10.1016/0092-8674(93)90628-4 · Cited by 1,072
VISTA : visualizing global DNA sequence alignments of arbitrary length
Mayor, C., Brudno, M., Schwartz, J. R., Poliakov, A., Rubin, E. M., Frazer, K. A., Pachter, L. S., & Dubchak, I. L. (2000) · Bioinformatics · doi:10.1093/bioinformatics/16.11.1046 · Cited by 1,017
Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly
Lettice, L., Horikoshi, T., Heaney, S., van Baren, M. V., van der Linde, H. C., Breedveld, G., Joosse, M., Akarsu, N., Oostra, B., Endo, N., et al. (2002) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.112212199 · Cited by 501
Self-citationThe regulation of myogenin gene expression during the embryonic development of the mouse.Preprint
Yee, S., & Rigby, P. W. J. (1993) · Genes & Development · doi:10.1101/gad.7.7a.1277 · Cited by 423
Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9
Li, H., Arber, S., Jessell, T. M., & Edlund, H. (1999) · Nature Genetics · doi:10.1038/12669 · Cited by 377
Position effect in human genetic disease
Kleinjan, D. A. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.10.1611 · Cited by 370
Research works printed but not linked: 1
- Sanders, J.W. Jr and Gasseling, M.T. (1968) Ectodermal-mesenchymal interactions in the origin of limb symmetry. In Fleischmajar, R. and Billingham, R.F. (eds), Ectodermal-Mesenchymal Interactions. Williams and Wilkins, Baltimore, MD, pp. 78-97.
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“The ZRS is the paradigm for long-range gene regulation, operating over 1 Mb to regulate Shh (Lettice et al., 2003; Sagai et al., 2005).”
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Spielmann, M., & Mundlos, S. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw205 · Cited by 154
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Gurnett, C. A., Alaee, F., Kruse, L. M., Desruisseau, D. M., Hecht, J. T., Wise, C. A., Bowcock, A. M., & Dobbs, M. B. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.10.004 · Cited by 150
Marinić, M., Aktaş, T., Ruf, S., & Spitz, F. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.01.025 · Cited by 149
Phylogenetic conservation of a limb-specific, cis-acting regulator of Sonic hedgehog (Shh)
Sagai, T., Masuya, H., Tamura, M., Shimizu, K., Yada, Y., Wakana, S., Gondo, Y., Noda, T., & Shiroishi, T. (2004) · Mammalian Genome · doi:10.1007/s00335-033-2317-5 · Cited by 163
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Smith, E. M., Lajoie, B. R., Jain, G., & Dekker, J. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.12.002 · Cited by 150
Dorshorst, B., Okimoto, R., & Ashwell, C. M. (2010) · Journal of Heredity · doi:10.1093/jhered/esp120 · Cited by 143
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Zúñiga, A. (2015) · Development · doi:10.1242/dev.125757 · Cited by 140
Chatterjee, S., Kapoor, A., Akiyama, J. A., Auer, D. R., Lee, D., Gabriel, S., Berrios, C., Pennacchio, L. A., & Chakravarti, A. (2016) · Cell · doi:10.1016/j.cell.2016.09.005 · Cited by 135
High-Resolution Epigenomic Atlas of Human Embryonic Craniofacial Development
Wilderman, A., VanOudenhove, J., Kron, J., Noonan, J. P., & Cotney, J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.129 · Cited by 139
Inversion-induced disruption of the Hoxd cluster leads to the partition of regulatory landscapes
Spitz, F., Herkenne, C., Morris, M. A., & Duboule, D. (2005) · Nature Genetics · doi:10.1038/ng1597 · Cited by 139
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Sakabe, N. J., Savic, D., & Nóbrega, M. A. (2012) · Genome biology · doi:10.1186/gb-2012-13-1-238 · Cited by 143
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Chatterjee, S., & Ahituv, N. (2017) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091416-035537 · Cited by 144
Hing, B., Sathyaputri, L., & Potash, J. B. (2018) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32616 · Cited by 137
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Dahn, R. D., Davis, M. C., Pappano, W. N., & Shubin, N. H. (2006) · Nature · doi:10.1038/nature05436 · Cited by 138
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Self-citationHook, P. W., McClymont, S. A., Cannon, G. H., Law, W. D., Morton, A. J., Goff, L. A., & McCallion, A. S. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.02.001 · Cited by 136
Functional Analysis of CTCF During Mammalian Limb Development
Soshnikova, N. V., Montavon, T., Leleu, M., Galjart, N., & Duboule, D. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.11.009 · Cited by 130
Jiang, Q., Arnold, S. M., Heanue, T. A., Kilambi, K. P., Doan, B. Q., Kapoor, A., Ling, A. Y., Sosa, M. X., Guy, M., Jiang, Q., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.02.014 · Cited by 133
Epigenomic evolution in diffuse large B-cell lymphomas
Pan, H., Jiang, Y., Boi, M., Tabbò, F., Redmond, D., Nie, K., Ladetto, M., Chiappella, A., Cerchietti, L. C. A., Shaknovich, R., et al. (2015) · Nature Communications · doi:10.1038/ncomms7921 · Cited by 129
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Antonarakis, S. E., & Epstein, C. J. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.08.005 · Cited by 139
Predicting tissue-specific enhancers in the human genomePreprint
Pennacchio, L. A., Loots, G. G., Nóbrega, M. A., & Ovcharenko, I. (2007) · Genome Research · doi:10.1101/gr.5972507 · Cited by 135
Andrey, G., Schöpflin, R., Jerković, I., Heinrich, V., Ibrahim, D. M., Paliou, C., Hochradel, M., Timmermann, B., Haas, S. A., Vingron, M., et al. (2016) · Genome Research · doi:10.1101/gr.213066.116 · Cited by 126
The three-dimensional genome: regulating gene expression during pluripotency and development
Andrey, G., & Mundlos, S. (2017) · Development · doi:10.1242/dev.148304 · Cited by 134
Wieczorek, D., Pawlik, B., Li, Y., Akarsu, N., Caliebe, A., May, K. J. W., Schweiger, B., Vargas, F., Balcı, S., Gillessen-kaesbach, G., et al. (2010) · Human Mutation · doi:10.1002/humu.21142 · Cited by 132
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Wu, H., Nord, A. S., Akiyama, J. A., Shoukry, M. I., Afzal, V., Rubin, E. M., Pennacchio, L. A., & Visel, A. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004610 · Cited by 129
Liu, J., & Krantz, I. D. (2008) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164211 · Cited by 131
Shh and ZRS enhancer colocalisation is specific to the zone of polarising activity
Williamson, I., Lettice, L. A., Hill, R. E., & Bickmore, W. A. (2016) · Development · doi:10.1242/dev.139188 · Cited by 124
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Maass, P. G., Rump, A., Schulz, H., Stricker, S., Schulze, L., Platzer, K., Aydın, A., Tinschert, S., Goldring, M. B., Luft, F. C., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci65508 · Cited by 124
Clinical Genetics of Polydactyly: An Updated Review
Umair, M., Ahmad, F., Bilal, M., Ahmad, W., & Alfadhel, M. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00447 · Cited by 122
Automated high-throughput mapping of promoter-enhancer interactions in zebrafish embryos
Gehrig, J., Reischl, M., Kalmár, É., Ferg, M., Hadzhiev, Y., Zaucker, A., Song, C., Schindler, S., Liebel, U., & Müller, F. (2009) · Nature Methods · doi:10.1038/nmeth.1396 · Cited by 123
MacDonald, B. T., Adamska, M., & Meisler, M. H. (2004) · Development · doi:10.1242/dev.01126 · Cited by 125
Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs
López-Rı́os, J., Duchesne, A., Speziale, D., Andrey, G., Peterson, K. A., Germann, P., Ünal, E., Liu, J., Floriot, S., Barbey, S., et al. (2014) · Nature · doi:10.1038/nature13289 · Cited by 115
Tan, J., Shenker-Tauris, N., Rodriguez-Hernaez, J., Wang, E., Sakellaropoulos, T., Boccalatte, F. E., Thandapani, P., Skok, J. A., Aifantis, I., Fenyö, D., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01612-8 · Cited by 123
Klopocki, E., Ott, C.-E., Benatar, N., Ullmann, R., Mundlos, S., & Lehmann, K. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2007.055699 · Cited by 118
Sabherwal, N., Bangs, F. K., Roth, R., Weiss, B., Jantz, K., Tiecke, E., Hinkel, G. K., Spaich, C., Hauffa, B. P., van der Kamp, H., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl470 · Cited by 120
Osterwalder, M., Speziale, D., Shoukry, M. I., Mohan, R. A., Ivánek, R., Kohler, M., Beisel, C., Wen, X., Scales, S. J., Christoffels, V. M., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.09.018 · Cited by 117
Genomic interactions: Chromatin loops and gene meeting points in transcriptional regulation
Sexton, T., Bantignies, F., & Cavalli, G. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.06.004 · Cited by 124
Beysen, D., Raes, J., Leroy, B. P., Lucassen, A., Yates, J. R. W., Clayton‐Smith, J., Ilyina, H. G., Brooks, S. S., Christin‐Maître, S., Fellous, M., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/432083 · Cited by 118
A computational pipeline for comparative ChIP-seq analyses
Bardet, A. F., He, Q., Zeitlinger, J., & Stark, A. (2011) · Nature Protocols · doi:10.1038/nprot.2011.420 · Cited by 118
A far downstream enhancer for murine Bcl11b controls its T-cell specific expression
Li, L., Zhang, J. A., Dose, M., Kueh, H. Y., Mosadeghi, R., Gounari, F., & Rothenberg, E. V. (2013) · Blood · doi:10.1182/blood-2012-08-447839 · Cited by 115
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Narlikar, L., Sakabe, N. J., Blanski, A. A., Arimura, F. E., Westlund, J. M., Nóbrega, M. A., & Ovcharenko, I. (2010) · Genome Research · doi:10.1101/gr.098657.109 · Cited by 121
Metrics of sequence constraint overlook regulatory sequences in an exhaustive analysis at phox2bPreprint
McGaughey, D. M., Vinton, R. M., Huynh, J. L., Al-Saif, A. M., Beer, M., & McCallion, A. S. (2007) · Genome Research · doi:10.1101/gr.6929408 · Cited by 114
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Epstein, D. J. (2009) · Briefings in Functional Genomics and Proteomics · doi:10.1093/bfgp/elp021 · Cited by 117
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Rinkwitz, S., Mourrain, P., & Becker, T. S. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.11.003 · Cited by 122
Sun, M., Ma, F., Zeng, X., Liu, Q., Xl, Z., Wu, F.-X., Wu, G., Zhang, Z.-F., Gu, B., Zhao, Y.-F., et al. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2008.057646 · Cited by 113
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Visel, A., Bristow, J. D., & Pennacchio, L. A. (2007) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2006.12.014 · Cited by 114
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Herz, H. (2016) · BioEssays · doi:10.1002/bies.201600106 · Cited by 110
Xu, B., Wratten, N. S., Charych, E. I., Buyske, S. G., Firestein, B. L., & Brzustowicz, L. M. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020263 · Cited by 111
Chromatin and epigenetic features of long-range gene regulation
Harmston, N., & Lenhard, B. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt499 · Cited by 113
Conserved non-coding elements: developmental gene regulation meets genome organization
Polychronopoulos, D., King, J. W. D., Nash, A. J., Tan, G., & Lenhard, B. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1074 · Cited by 111
Loss and Re-emergence of Legs in Snakes by Modular Evolution of Sonic hedgehog and HOXD Enhancers
Leal, F., & Cohn, M. J. (2016) · Current Biology · doi:10.1016/j.cub.2016.09.020 · Cited by 112
Cherry, T. J., Yang, M. G., Harmin, D. A., Tao, P., Timms, A. E., Bauwens, M., Allikmets, R. L., Jones, E., Chen, R., Baere, E. D., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922501117 · Cited by 101
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Self-citationMoore, J. E., Pratt, H. E., Purcaro, M. J., & Weng, Z. (2020) · Genome Biology · doi:10.1186/s13059-019-1924-8 · Cited by 106
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McEwen, G. K., Woolfe, A., Goode, D. K., Vavouri, T., Callaway, H., & Elgar, G. (2006) · Genome Research · doi:10.1101/gr.4143406 · Cited by 105
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Sagai, T., Amano, T., Tamura, M., Mizushina, Y., Sumiyama, K., & Shiroishi, T. (2009) · Development · doi:10.1242/dev.032714 · Cited by 105
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Muerdter, F., Boryń, Ł. M., & Arnold, C. D. (2015) · Genomics · doi:10.1016/j.ygeno.2015.06.001 · Cited by 109
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Leipoldt, M., Erdel, M., Bien-Willner, G. A., Smyk, M., Theurl, M., Yatsenko, S. A., Lupski, J. R., Lane, A., Shanske, A. L., Stankiewicz, P., et al. (2006) · Clinical Genetics · doi:10.1111/j.1399-0004.2007.00736.x · Cited by 101
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Lim, F., Solvason, J. J., Ryan, G. E., Le, S. H., Jindal, G. A., Steffen, P., Jandu, S. K., & Farley, E. K. (2024) · Nature · doi:10.1038/s41586-023-06922-8 · Cited by 102
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Kathiriya, I. S., Nora, E. P., & Bruneau, B. G. (2015) · Circulation Research · doi:10.1161/circresaha.116.302832 · Cited by 100
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Kleinjan, D. A., & Lettice, L. A. (2008) · Advances in genetics · doi:10.1016/s0065-2660(07)00013-2 · Cited by 97
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Anderson, E., Peluso, S., Lettice, L. A., & Hill, R. E. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.03.012 · Cited by 97
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Dickel, D. E., Barozzi, I., Zhu, Y., Fukuda-Yuzawa, Y., Osterwalder, M., Mannion, B. J., May, D., Spurrell, C. H., Plajzer-Frick, I., Pickle, C. S., et al. (2016) · Nature Communications · doi:10.1038/ncomms12923 · Cited by 93
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Ng, C. E. L., Yokomizo, T., Yamashita, N., Cirovic, B., Jin, H., Wen, Z., Ito, Y., & Osato, M. (2010) · Stem Cells · doi:10.1002/stem.507 · Cited by 95
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Koshikawa, S., Giorgianni, M. W., Vaccaro, K., Kassner, V. A., Yoder, J. H., Werner, T., & Carroll, S. B. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1509022112 · Cited by 97
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Grenn, F. P., Kim, J. J., Makarious, M. B., Iwaki, H., Illarionova, A., Brolin, K., Kluss, J. H., Schumacher‐Schuh, A. F., Leonard, H., Faghri, F., et al. (2020) · Movement Disorders · doi:10.1002/mds.28197 · Cited by 92
D′haene, B., Attanasio, C., Beysen, D., Dostie, J., Lemire, E. G., Bouchard, P., Field, M., Jones, K., Lorenz, B., Menten, B., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000522 · Cited by 97
Xiong, L., Catoire, H., Dion, P. A., Gaspar, C., Lafrenière, R. G., Girard, S., Levchenko, А., Rivière, J., Fiori, L. M., St‐Onge, J., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddn443 · Cited by 96
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Zentner, G. E., & Scacheri, P. C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.296491 · Cited by 92
Matharu, N. K., & Ahituv, N. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005640 · Cited by 99
Anderson, A. G., Rogers, B. B., Loupe, J. M., Rodriguez-Nunez, I., Roberts, S. C., White, L. M., Brazell, J. N., Bunney, W. E., Bunney, B. G., Watson, S. J., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100263 · Cited by 82
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Tena, J. J., Alonso, M. E., de la Calle‐Mustienes, E., Splinter, E., de Laat, W. L., Manzanares, M., & Gómez-Skármeta, J. L. (2011) · Nature Communications · doi:10.1038/ncomms1301 · Cited by 88
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Salinas, C. A., Kwon, E. M., Carlson, C. S., Koopmeiners, J. S., Feng, Z., Karyadi, D. M., Ostrander, E. A., & Stanford, J. L. (2008) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-07-2811 · Cited by 84
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de Laat, W. L., Klous, P., Kooren, J. A., Noordermeer, D., Palstra, R.-J. T. S., Simonis, M., Splinter, E., & Grosveld, F. G. (2008) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(07)00005-1 · Cited by 87
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Reymond, A., Hor, C. N., Harewood, L., & Merla, G. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2007.08.009 · Cited by 84
Brown, K. K., Reiss, J. A., Crow, K., Ferguson, H. L., Kelly, C., Fritzsch, B., & Morton, C. C. (2009) · Human Genetics · doi:10.1007/s00439-009-0736-4 · Cited by 85
Cajigas, I., Chakraborty, A., Swyter, K. R., Luo, H., Bastidas, M., Nigro, M., Morris, E. R., Chen, S., VanGompel, M. J. W., Leib, D., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.07.024 · Cited by 82
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Metadata
- Authors
- Lettice, L. A.
- Affiliations
- Western General Hospital (GB)
- Corresponding author
- Lettice, L. A.
- ORCID
- Lettice, L. A.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-07-15
- Volume
- 12
- Issue
- 14
- Pages
- 1725-1735
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2145144631
- Cited by
- 1,164
- References
- 35
- Citations by year
- 2026: 26 · 2025: 40 · 2024: 50 · 2023: 58 · 2022: 66 · 2021: 78 · 2020: 52 · 2019: 49 · 2018: 50 · 2017: 50 · 2016: 64 · 2015: 56 · 2014: 78 · 2013: 64 · 2012: 60
- FWCI
- 26.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Lirias (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- Sonic hedgehog, preaxial polydactyly, limb bud, fin development, zirconium, LMBR1, point mutations, congenital limb anomalies, chromosome 7q36
- MeSH terms
- Zona Pellucida Glycoproteins, Animals, Base Sequence, Chromosomes, Human, Pair 7, Egg Proteins, Enhancer Elements, Genetic, Extremities, Female, Humans, Male, Membrane Glycoproteins, Membrane Proteins, Molecular Sequence Data, Pedigree, Receptors, Cell Surface, Trans-Activators, Polydactyly, Takifugu, Mice, Hedgehog Proteins
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