The Necessity for In Vivo Functional Analysis in Human Medical Genetics.
Main Article Content
Abstract
Approximately 50% of all congenital anomalies cannot be linked to any specific cause, but cost effective high throughput sequencing has emerged as an efficient strategy for identifying single nucleotide polymorphisms (SNPs) associated with disease. In many cases, there is not enough evidence to determine if these SNPs underlie disease. To bridge this gap in our understanding, advances in functional analyses are warranted. Several preclinical model systems are currently being utilized to provide such evidence, including the advantageous zebrafish embryo. While every system exhibits disadvantages and caveats, a new era of multidisciplinary research is emerging, which uses a broad spectrum of functional analysis tools. This approach will make it possible to identify potential therapeutic targets for both common and rare human disorders.
Article Details
How to Cite
QUINTANA, Anita M.
The Necessity for In Vivo Functional Analysis in Human Medical Genetics..
Medical Research Archives, [S.l.], v. 2, n. 8, nov. 2015.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/393>. Date accessed: 22 dec. 2024.
Keywords
functional analysis, zebrafish, multiple congenital anomalies
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
Aerts, J., Wetzels, Y., Cohen, N., & Aerssens, J. (2002). Data mining of public SNP databases for the selection of intragenic SNPs. Human Mutation, 20(3), 162–173. http://doi.org/10.1002/humu.10107
Armstrong, A. J., & Zhang, T. (2015). Docetaxel Resistance in Prostate Cancer: Taking It Up a Notch. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. http://doi.org/10.1158/1078-0432.CCR-15-1613
Barbosa, J. S., Sanchez-Gonzalez, R., Di Giaimo, R., Baumgart, E. V., Theis, F. J., Götz, M., & Ninkovic, J. (2015). Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain. Science (New York, N.Y.), 348(6236), 789–793. http://doi.org/10.1126/science.aaa2729
Bjornsson, H. T., Benjamin, J. S., Zhang, L., Weissman, J., Gerber, E. E., Chen, Y.-C., … Dietz, H. C. (2014). Histone deacetylase inhibition rescues structural and functional brain deficits in a mouse model of Kabuki syndrome. Science Translational Medicine, 6(256), 256ra135. http://doi.org/10.1126/scitranslmed.3009278
Blackburn, P. R., Campbell, J. M., Clark, K. J., & Ekker, S. C. (2013). The CRISPR System-Keeping Zebrafish Gene Targeting Fresh. Zebrafish, 10(1), 116–118. http://doi.org/10.1089/zeb.2013.9999
Borecki, I. B., & Province, M. A. (2008). Linkage and association: basic concepts. Advances in Genetics, 60, 51–74. http://doi.org/10.1016/S0065-2660(07)00403-8
Botstein, D., & Risch, N. (2003). Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease. Nature Genetics, 33, 228–237. http://doi.org/10.1038/ng1090
Brinkman, R. R., Dubé, M.-P., Rouleau, G. A., Orr, A. C., & Samuels, M. E. (2006). Human monogenic disorders — a source of novel drug targets. Nature Reviews Genetics, 7(4), 249–260. http://doi.org/10.1038/nrg1828
Byrne, S. M., Mali, P., & Church, G. M. (2014). Genome editing in human stem cells. Methods in Enzymology, 546, 119–138. http://doi.org/10.1016/B978-0-12-801185-0.00006-4
Carrillo-Carrasco, N., Adams, D., & Venditti, C. P. (1993). Disorders of Intracellular Cobalamin Metabolism. In R. A. Pagon, M. P. Adam, T. D. Bird, C. R. Dolan, C.-T. Fong, R. J. Smith, & K. Stephens (Eds.), GeneReviewsTM. Seattle (WA): University of Washington, Seattle. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1328/
Cheon, C. K., Sohn, Y. B., Ko, J. M., Lee, Y. J., Song, J. S., Moon, J. W., … Jeong, S.-Y. (2014). Identification of KMT2D and KDM6A mutations by exome sequencing in Korean patients with Kabuki syndrome. Journal of Human Genetics, 59(6), 321–325. http://doi.org/10.1038/jhg.2014.25
Clark, K. J., Voytas, D. F., & Ekker, S. C. (2011). A TALE of two nucleases: gene targeting for the masses? Zebrafish, 8(3), 147–149. http://doi.org/10.1089/zeb.2011.9993
Coughlin, C. R., Scharer, G. H., Friederich, M. W., Yu, H.-C., Geiger, E. A., Creadon-Swindell, G., … Shaikh, T. H. (2015). Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. Journal of Medical Genetics, 52(8), 532–540.
http://doi.org/10.1136/jmedgenet-2015-103049
Drosophila: , the golden bug, emerges as a tool for human genetics : Article : Nature Reviews Genetics. (n.d.). Retrieved August 24, 2015, from http://www.nature.com/nrg/journal/v6/n1/full/nrg1503.html
Eisen, J. S., & Smith, J. C. (2008). Controlling morpholino experiments: don’t stop making antisense. Development (Cambridge, England), 135(10), 1735–1743. http://doi.org/10.1242/dev.001115
Ford, D. J., & Dingwall, A. K. (2015). The cancer COMPASS: navigating the functions of MLL complexes in cancer. Cancer Genetics, 208(5), 178–191. http://doi.org/10.1016/j.cancergen.2015.01.005
Frantz, S. (2004). FDA publishes analysis of the pipeline problem. Nature Reviews Drug Discovery, 3(5), 379–379. http://doi.org/10.1038/nrd1404
Fung, Y. K., Murphree, A. L., T’Ang, A., Qian, J., Hinrichs, S. H., & Benedict, W. F. (1987). Structural evidence for the authenticity of the human retinoblastoma gene. Science (New York, N.Y.), 236(4809), 1657–1661.
Gérard, M., Morin, G., Bourillon, A., Colson, C., Mathieu, S., Rabier, D., … Benoist, J. F. (2015a). Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder. European Journal of Medical Genetics, 58(3), 148–153. http://doi.org/10.1016/j.ejmg.2014.12.015
Gérard, M., Morin, G., Bourillon, A., Colson, C., Mathieu, S., Rabier, D., … Benoist, J. F. (2015b). Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder. European Journal of Medical Genetics, 58(3), 148–153. http://doi.org/10.1016/j.ejmg.2014.12.015
Gerety, S. S., & Wilkinson, D. G. (2011). Morpholino artifacts provide pitfalls and reveal a novel role for pro-apoptotic genes in hindbrain boundary development. Developmental Biology, 350(2), 279–289. http://doi.org/10.1016/j.ydbio.2010.11.030
Guo, C., Chang, C.-C., Wortham, M., Chen, L. H., Kernagis, D. N., Qin, X., … He, Y. (2012). Global identification of MLL2-targeted loci reveals MLL2’s role in diverse signaling pathways. Proceedings of the National Academy of Sciences of the United States of America, 109(43), 17603–17608. http://doi.org/10.1073/pnas.1208807109
Hannibal, L., Kim, J., Brasch, N. E., Wang, S., Rosenblatt, D. S., Banerjee, R., & Jacobsen, D. W. (2009). Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product. Molecular Genetics and Metabolism, 97(4), 260–266.
http://doi.org/10.1016/j.ymgme.2009.04.005
Hehir-Kwa, J. Y., Pfundt, R., & Veltman, J. A. (2015). Exome sequencing and whole genome sequencing for the detection of copy number variation. Expert Review of Molecular Diagnostics, 1–10. http://doi.org/10.1586/14737159.2015.1053467
Henikoff, S., Till, B. J., & Comai, L. (2004). TILLING. Traditional mutagenesis meets functional genomics. Plant Physiology, 135(2), 630–636. http://doi.org/10.1104/pp.104.041061
Hines, J. H., Ravanelli, A. M., Schwindt, R., Scott, E. K., & Appel, B. (2015). Neuronal activity biases axon selection for myelination in vivo. Nature Neuroscience, 18(5), 683–689. http://doi.org/10.1038/nn.3992
Houdebine, L. M., & Chourrout, D. (1991). Transgenesis in fish. Experientia, 47(9), 891–897.
Howe, K., Clark, M. D., Torroja, C. F., Torrance, J., Berthelot, C., Muffato, M., … Stemple, D. L. (2013). The zebrafish reference genome sequence and its relationship to the human genome. Nature, 496(7446), 498–503. http://doi.org/10.1038/nature12111
Huang, L., Jolly, L. A., Willis-Owen, S., Gardner, A., Kumar, R., Douglas, E., … Gecz, J. (2012). A Noncoding, Regulatory Mutation Implicates HCFC1 in Nonsyndromic Intellectual Disability. American Journal of Human Genetics, 91(4), 694–702. http://doi.org/10.1016/j.ajhg.2012.08.011
Hwang, W. Y., Fu, Y., Reyon, D., Gonzales, A. P. W., Joung, J. K., & Yeh, J.-R. J. (2015). Targeted Mutagenesis in Zebrafish Using CRISPR RNA-Guided Nucleases. Methods in Molecular Biology (Clifton, N.J.), 1311, 317–334. http://doi.org/10.1007/978-1-4939-2687-9_21
Hwang, W. Y., Fu, Y., Reyon, D., Maeder, M. L., Tsai, S. Q., Sander, J. D., … Joung, J. K. (2013). Efficient genome editing in zebrafish using a CRISPR-Cas system. Nature Biotechnology, 31(3), 227–229. http://doi.org/10.1038/nbt.2501
Insights from human/mouse genome comparisons - art%3A10.1007%2Fs00335-002-4001-1.pdf. (n.d.). Retrieved August 24, 2015, from http://download.springer.com/static/pdf/244/art%253A10.1007%252Fs00335-002-4001-1.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs00335-002-4001-1&token2=exp=1440449210~acl=%2Fstatic%2Fpdf%2F244%2Fart%25253A10.1007%25252Fs00335-002-4001-1.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs00335-002-4001-1*~hmac=c9c2c701c8bfdf12588b6f783c8bc36e6a85fe7b8ff545e44c1d474c8b308d14
Je, E. M., Lee, S. H., Yoo, N. J., & Lee, S. H. (2013). Mutational and expressional analysis of MLL genes in gastric and colorectal cancers with microsatellite instability. Neoplasma, 60(2), 188–195.
Johansen Taber, K. A., Dickinson, B. D., & Wilson, M. (2014). The promise and challenges of next-generation genome sequencing for clinical care. JAMA Internal Medicine, 174(2), 275–280. http://doi.org/10.1001/jamainternmed.2013.12048
Jolly, L. A., Nguyen, L. S., Domingo, D., Sun, Y., Barry, S., Hancarova, M., … Gecz, J. (2015). HCFC1 loss-of-function mutations disrupt neuronal and neural progenitor cells of the developing brain. Human Molecular Genetics. http://doi.org/10.1093/hmg/ddv083
Kalueff, A. V., Stewart, A. M., & Gerlai, R. (2014). Zebrafish as an emerging model for studying complex brain disorders. Trends in Pharmacological Sciences, 35(2), 63–75. http://doi.org/10.1016/j.tips.2013.12.002
Karki, R., Pandya, D., Elston, R. C., & Ferlini, C. (2015). Defining “mutation” and “polymorphism” in the era of personal genomics. BMC Medical Genomics, 8, 37. http://doi.org/10.1186/s12920-015-0115-z
Kawakami, K. (2005). Transposon tools and methods in zebrafish. Developmental Dynamics: An Official Publication of the American Association of Anatomists, 234(2), 244–254. http://doi.org/10.1002/dvdy.20516
Kerem, B., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., … Tsui, L. C. (1989). Identification of the cystic fibrosis gene: genetic analysis. Science (New York, N.Y.), 245(4922), 1073–1080.
Kirby, B. B., Takada, N., Latimer, A. J., Shin, J., Carney, T. J., Kelsh, R. N., & Appel, B. (2006). In vivo time-lapse imaging shows dynamic oligodendrocyte progenitor behavior during zebrafish development. Nature Neuroscience, 9(12), 1506–1511. http://doi.org/10.1038/nn1803
Kwan, K. M., Fujimoto, E., Grabher, C., Mangum, B. D., Hardy, M. E., Campbell, D. S., … Chien, C.-B. (2007). The Tol2kit: a multisite gateway-based construction kit for Tol2 transposon transgenesis constructs. Developmental Dynamics: An Official Publication of the American Association of Anatomists, 236(11), 3088–3099. http://doi.org/10.1002/dvdy.21343
Lan, F., Bayliss, P. E., Rinn, J. L., Whetstine, J. R., Wang, J. K., Chen, S., … Shi, Y. (2007). A histone H3 lysine 27 demethylase regulates animal posterior development. Nature, 449(7163), 689–694. http://doi.org/10.1038/nature06192
Lederer, D., Grisart, B., Digilio, M. C., Benoit, V., Crespin, M., Ghariani, S. C., … Verellen-Dumoulin, C. (2012). Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. American Journal of Human Genetics, 90(1), 119–124. http://doi.org/10.1016/j.ajhg.2011.11.021
Lee, H., Deignan, J. L., Dorrani, N., Strom, S. P., Kantarci, S., Quintero-Rivera, F., … Nelson, S. F. (2014). Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA, 312(18), 1880–1887. http://doi.org/10.1001/jama.2014.14604
Leong, I. U. S., Lai, D., Lan, C.-C., Johnson, R., Love, D. R., Johnson, R., & Love, D. R. (2011). Targeted mutagenesis of zebrafish: use of zinc finger nucleases. Birth Defects Research. Part C, Embryo Today: Reviews, 93(3), 249–255. http://doi.org/10.1002/bdrc.20213
Lindgren, A. M., Hoyos, T., Talkowski, M. E., Hanscom, C., Blumenthal, I., Chiang, C., … Morton, C. C. (2013). Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate. Human Genetics, 132(5), 537–552. http://doi.org/10.1007/s00439-013-1263-x
Lin, L., Bolund, L., & Luo, Y. (2015). Towards personalized regenerative cell therapy: Mesenchymal stem cells derived from human induced pluripotent stem cells. Current Stem Cell Research & Therapy.
Liu, M.-Y., Yang, Y.-L., Chang, Y.-C., Chiang, S.-H., Lin, S.-P., Han, L.-S., … Liu, T.-T. (2010). Mutation spectrum of MMACHC in Chinese patients with combined methylmalonic aciduria and homocystinuria. Journal of Human Genetics, 55(9), 621–626. http://doi.org/10.1038/jhg.2010.81
Li, Y., Bögershausen, N., Alanay, Y., Simsek Kiper, P. O., Plume, N., Keupp, K., … Wollnik, B. (2011). A mutation screen in patients with Kabuki syndrome. Human Genetics, 130(6), 715–724. http://doi.org/10.1007/s00439-011-1004-y
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., … Church, G. M. (2013). RNA-guided human genome engineering via Cas9. Science (New York, N.Y.), 339(6121), 823–826. http://doi.org/10.1126/science.1232033
Martin, C., & Zhang, Y. (2005). The diverse functions of histone lysine methylation. Nature Reviews Molecular Cell Biology, 6(11), 838–849. http://doi.org/10.1038/nrm1761
Mathews, E. S., Mawdsley, D. J., Walker, M., Hines, J. H., Pozzoli, M., & Appel, B. (2014). Mutation of 3-hydroxy-3-methylglutaryl CoA synthase I reveals requirements for isoprenoid and cholesterol synthesis in oligodendrocyte migration arrest, axon wrapping, and myelin gene expression. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 34(9), 3402–3412. http://doi.org/10.1523/JNEUROSCI.4587-13.2014
Melvin, V. S., Feng, W., Hernandez-Lagunas, L., Artinger, K. B., & Williams, T. (2013). A morpholino-based screen to identify novel genes involved in craniofacial morphogenesis. Developmental Dynamics: An Official Publication of the American Association of Anatomists, 242(7), 817–831. http://doi.org/10.1002/dvdy.23969
Michaud, J., Praz, V., Faresse, N. J., Jnbaptiste, C. K., Tyagi, S., Schütz, F., & Herr, W. (2013). HCFC1 is a common component of active human CpG-island promoters and coincides with ZNF143, THAP11, YY1, and GABP transcription factor occupancy. Genome Research. http://doi.org/10.1101/gr.150078.112
Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P. A., Harshman, K., Tavtigian, S., … Ding, W. (1994). A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science (New York, N.Y.), 266(5182), 66–71.
Miyake, N., Koshimizu, E., Okamoto, N., Mizuno, S., Ogata, T., Nagai, T., … Niikawa, N. (2013). MLL2 and KDM6A mutations in patients with Kabuki syndrome. American Journal of Medical Genetics. Part A, 161A(9), 2234–2243. http://doi.org/10.1002/ajmg.a.36072
Moens, C. B., Donn, T. M., Wolf-Saxon, E. R., & Ma, T. P. (2008). Reverse genetics in zebrafish by TILLING. Briefings in Functional Genomics & Proteomics, 7(6), 454–459. http://doi.org/10.1093/bfgp/eln046
Moscou, M. J., & Bogdanove, A. J. (2009). A simple cipher governs DNA recognition by TAL effectors. Science (New York, N.Y.), 326(5959), 1501. http://doi.org/10.1126/science.1178817
Mouse Genome Sequencing Consortium, Waterston, R. H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J. F., … Lander, E. S. (2002). Initial sequencing and comparative analysis of the mouse genome. Nature, 420(6915), 520–562. http://doi.org/10.1038/nature01262
Natarajan, T. G., Kallakury, B. V., Sheehan, C. E., Bartlett, M. B., Ganesan, N., Preet, A., … Fitzgerald, K. T. (2010). Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon. Cancer Cell International, 10, 13. http://doi.org/10.1186/1475-2867-10-13
Ng, S. B., Bigham, A. W., Buckingham, K. J., Hannibal, M. C., McMillin, M. J., Gildersleeve, H. I., … Shendure, J. (2010). Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nature Genetics, 42(9), 790–793. http://doi.org/10.1038/ng.646
Ng, S. B., Buckingham, K. J., Lee, C., Bigham, A. W., Tabor, H. K., Dent, K. M., … Bamshad, M. J. (2010). Exome sequencing identifies the cause of a mendelian disorder. Nature Genetics, 42(1), 30–35. http://doi.org/10.1038/ng.499
Niikawa, N., Matsuura, N., Fukushima, Y., Ohsawa, T., & Kajii, T. (1981). Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. The Journal of Pediatrics, 99(4), 565–569.
Ooki, S. (2012). Multiple Congenital Anomalies after Assisted Reproductive Technology in Japan (between 2004 and 2009). International Scholarly Research Notices, 2013, e452085. http://doi.org/10.5402/2013/452085
Pelegri, F. J. (Ed.). (2011). Inducing High Rates of Targeted Mutagenesis in Zebrafish Using Zinc Finger Nucleases (ZFNs) - Springer. Humana Press. Retrieved from http://link.springer.com/protocol/10.1007%2F978-1-61779-210-6_20
Quintana, A. M., Geiger, E. A., Achilly, N., Rosenblatt, D. S., Maclean, K. N., Stabler, S. P., … Shaikh, T. H. (2014). Hcfc1b, a zebrafish ortholog of HCFC1, regulates craniofacial development by modulating mmachc expression. Developmental Biology, 396(1), 94–106. http://doi.org/10.1016/j.ydbio.2014.09.026
Rabbani, B., Mahdieh, N., Hosomichi, K., Nakaoka, H., & Inoue, I. (2012). Next-generation sequencing: impact of exome sequencing in characterizing Mendelian disorders. Journal of Human Genetics, 57(10), 621–632. http://doi.org/10.1038/jhg.2012.91
Rabello, D. do A., de Moura, C. A., de Andrade, R. V., Motoyama, A. B., & Silva, F. P. (2013). Altered expression of MLL methyltransferase family genes in breast cancer. International Journal of Oncology, 43(2), 653–660. http://doi.org/10.3892/ijo.2013.1981
Sams-Dodd, F. (2005). Target-based drug discovery: is something wrong? Drug Discovery Today, 10(2), 139–147. http://doi.org/10.1016/S1359-6446(04)03316-1
Sanderson, L. E., Chien, A.-T., Astin, J. W., Crosier, K. E., Crosier, P. S., & Hall, C. J. (2015). An inducible transgene reports activation of macrophages in live zebrafish larvae. Developmental and Comparative Immunology, 53(1), 63–69. http://doi.org/10.1016/j.dci.2015.06.013
Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., … Shiloh, Y. (1995). A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science (New York, N.Y.), 268(5218), 1749–1753.
Ségalat, L. (2007). Invertebrate animal models of diseases as screening tools in drug discovery. ACS Chemical Biology, 2(4), 231–236. http://doi.org/10.1021/cb700009m
Shimizu, T., & Nakagawa, K. (2015). [Novel signal transduction pathways: the molecular basis for targeted cancer therapies in Hedgehog/Notch/Wnt pathway]. Nihon Rinsho. Japanese Journal of Clinical Medicine, 73(8), 1342–1348.
Simpson, M. A., Irving, M. D., Asilmaz, E., Gray, M. J., Dafou, D., Elmslie, F. V., … Trembath, R. C. (2011). Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nature Genetics, 43(4), 303–305. http://doi.org/10.1038/ng.779
Smith, E., Lin, C., & Shilatifard, A. (2011). The super elongation complex (SEC) and MLL in development and disease. Genes & Development, 25(7), 661–672. http://doi.org/10.1101/gad.2015411
Snyder, J. L., Kearns, C. A., & Appel, B. (2012). Fbxw7 regulates Notch to control specification of neural precursors for oligodendrocyte fate. Neural Development, 7, 15. http://doi.org/10.1186/1749-8104-7-15
Summerton, J. E. (2007). Morpholino, siRNA, and S-DNA compared: impact of structure and mechanism of action on off-target effects and sequence specificity. Current Topics in Medicinal Chemistry, 7(7), 651–660.
Sun, N., & Zhao, H. (2013). Transcription activator-like effector nucleases (TALENs): a highly efficient and versatile tool for genome editing. Biotechnology and Bioengineering, 110(7), 1811–1821. http://doi.org/10.1002/bit.24890
Suster, M. L., Kikuta, H., Urasaki, A., Asakawa, K., & Kawakami, K. (2009). Transgenesis in zebrafish with the tol2 transposon system. Methods in Molecular Biology (Clifton, N.J.), 561, 41–63. http://doi.org/10.1007/978-1-60327-019-9_3
Taylor, E. W., Xu, J., Jabs, E. W., & Meyers, D. A. (1997). Linkage analysis of genetic disorders. Methods in Molecular Biology (Clifton, N.J.), 68, 11–25.
Taylor, J. S., Van de Peer, Y., Braasch, I., & Meyer, A. (2001). Comparative genomics provides evidence for an ancient genome duplication event in fish. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 356(1414), 1661–1679. http://doi.org/10.1098/rstb.2001.0975
Tzur, Y. B., Friedland, A. E., Nadarajan, S., Church, G. M., Calarco, J. A., & Colaiácovo, M. P. (2013). Heritable custom genomic modifications in Caenorhabditis elegans via a CRISPR-Cas9 system. Genetics, 195(3), 1181–1185. http://doi.org/10.1534/genetics.113.156075
Vandenbergh, J. G. (2000). Use of House Mice in Biomedical Research. ILAR Journal, 41(3), 133–135. http://doi.org/10.1093/ilar.41.3.133
Van Laarhoven, P. M., Neitzel, L. R., Quintana, A. M., Geiger, E. A., Zackai, E. H., Clouthier, D. E., … Shaikh, T. H. (2015). Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development. Human Molecular Genetics. http://doi.org/10.1093/hmg/ddv180
Weisfeld-Adams, J. D., Bender, H. A., Miley-Åkerstedt, A., Frempong, T., Schrager, N. L., Patel, K., … Diaz, G. A. (2013). Neurologic and neurodevelopmental phenotypes in young children with early-treated combined methylmalonic acidemia and homocystinuria, cobalamin C type. Molecular Genetics and Metabolism, 110(3), 241–247. http://doi.org/10.1016/j.ymgme.2013.07.018
Welte, Y., Davies, C., Schäfer, R., & Regenbrecht, C. R. A. (2013). Patient derived cell culture and isolation of CD133+ putative cancer stem cells from melanoma. Journal of Visualized Experiments: JoVE, (73), e50200. http://doi.org/10.3791/50200
Winkler, S., Gscheidel, N., & Brand, M. (2011). Mutant generation in vertebrate model organisms by TILLING. Methods in Molecular Biology (Clifton, N.J.), 770, 475–504. http://doi.org/10.1007/978-1-61779-210-6_19
Yin, L., Jao, L.-E., & Chen, W. (2015). Generation of Targeted Mutations in Zebrafish Using the CRISPR/Cas System. Methods in Molecular Biology (Clifton, N.J.), 1332, 205–217. http://doi.org/10.1007/978-1-4939-2917-7_16
Yin, S., Yang, J., Lin, B., Deng, W., Zhang, Y., Yi, X., … Kong, X. (2014). Exome sequencing identifies frequent mutation of MLL2 in non-small cell lung carcinoma from Chinese patients. Scientific Reports, 4, 6036. http://doi.org/10.1038/srep06036
Yuan, X., Wu, H., Xu, H., Xiong, H., Chu, Q., Yu, S., … Wu, K. (2015). Notch signaling: An emerging therapeutic target for cancer treatment. Cancer Letters. http://doi.org/10.1016/j.canlet.2015.07.048
Yu, H.-C., Geiger, E. A., Medne, L., Zackai, E. H., & Shaikh, T. H. (2014). An individual with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and additional features expands the phenotype associated with mutations in KAT6B. American Journal of Medical Genetics. Part A. http://doi.org/10.1002/ajmg.a.36379
Yu, H.-C., Sloan, J. L., Scharer, G., Brebner, A., Quintana, A. M., Achilly, N. P., … Shaikh, T. H. (2013). An X-Linked Cobalamin Disorder Caused by Mutations in Transcriptional Coregulator HCFC1. American Journal of Human Genetics, 93(3), 506–514. http://doi.org/10.1016/j.ajhg.2013.07.022
Zhang, X. (2014). Exome sequencing greatly expedites the progressive research of Mendelian diseases. Frontiers of Medicine, 8(1), 42–57. http://doi.org/10.1007/s11684-014-0303-9
Armstrong, A. J., & Zhang, T. (2015). Docetaxel Resistance in Prostate Cancer: Taking It Up a Notch. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. http://doi.org/10.1158/1078-0432.CCR-15-1613
Barbosa, J. S., Sanchez-Gonzalez, R., Di Giaimo, R., Baumgart, E. V., Theis, F. J., Götz, M., & Ninkovic, J. (2015). Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain. Science (New York, N.Y.), 348(6236), 789–793. http://doi.org/10.1126/science.aaa2729
Bjornsson, H. T., Benjamin, J. S., Zhang, L., Weissman, J., Gerber, E. E., Chen, Y.-C., … Dietz, H. C. (2014). Histone deacetylase inhibition rescues structural and functional brain deficits in a mouse model of Kabuki syndrome. Science Translational Medicine, 6(256), 256ra135. http://doi.org/10.1126/scitranslmed.3009278
Blackburn, P. R., Campbell, J. M., Clark, K. J., & Ekker, S. C. (2013). The CRISPR System-Keeping Zebrafish Gene Targeting Fresh. Zebrafish, 10(1), 116–118. http://doi.org/10.1089/zeb.2013.9999
Borecki, I. B., & Province, M. A. (2008). Linkage and association: basic concepts. Advances in Genetics, 60, 51–74. http://doi.org/10.1016/S0065-2660(07)00403-8
Botstein, D., & Risch, N. (2003). Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease. Nature Genetics, 33, 228–237. http://doi.org/10.1038/ng1090
Brinkman, R. R., Dubé, M.-P., Rouleau, G. A., Orr, A. C., & Samuels, M. E. (2006). Human monogenic disorders — a source of novel drug targets. Nature Reviews Genetics, 7(4), 249–260. http://doi.org/10.1038/nrg1828
Byrne, S. M., Mali, P., & Church, G. M. (2014). Genome editing in human stem cells. Methods in Enzymology, 546, 119–138. http://doi.org/10.1016/B978-0-12-801185-0.00006-4
Carrillo-Carrasco, N., Adams, D., & Venditti, C. P. (1993). Disorders of Intracellular Cobalamin Metabolism. In R. A. Pagon, M. P. Adam, T. D. Bird, C. R. Dolan, C.-T. Fong, R. J. Smith, & K. Stephens (Eds.), GeneReviewsTM. Seattle (WA): University of Washington, Seattle. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1328/
Cheon, C. K., Sohn, Y. B., Ko, J. M., Lee, Y. J., Song, J. S., Moon, J. W., … Jeong, S.-Y. (2014). Identification of KMT2D and KDM6A mutations by exome sequencing in Korean patients with Kabuki syndrome. Journal of Human Genetics, 59(6), 321–325. http://doi.org/10.1038/jhg.2014.25
Clark, K. J., Voytas, D. F., & Ekker, S. C. (2011). A TALE of two nucleases: gene targeting for the masses? Zebrafish, 8(3), 147–149. http://doi.org/10.1089/zeb.2011.9993
Coughlin, C. R., Scharer, G. H., Friederich, M. W., Yu, H.-C., Geiger, E. A., Creadon-Swindell, G., … Shaikh, T. H. (2015). Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. Journal of Medical Genetics, 52(8), 532–540.
http://doi.org/10.1136/jmedgenet-2015-103049
Drosophila: , the golden bug, emerges as a tool for human genetics : Article : Nature Reviews Genetics. (n.d.). Retrieved August 24, 2015, from http://www.nature.com/nrg/journal/v6/n1/full/nrg1503.html
Eisen, J. S., & Smith, J. C. (2008). Controlling morpholino experiments: don’t stop making antisense. Development (Cambridge, England), 135(10), 1735–1743. http://doi.org/10.1242/dev.001115
Ford, D. J., & Dingwall, A. K. (2015). The cancer COMPASS: navigating the functions of MLL complexes in cancer. Cancer Genetics, 208(5), 178–191. http://doi.org/10.1016/j.cancergen.2015.01.005
Frantz, S. (2004). FDA publishes analysis of the pipeline problem. Nature Reviews Drug Discovery, 3(5), 379–379. http://doi.org/10.1038/nrd1404
Fung, Y. K., Murphree, A. L., T’Ang, A., Qian, J., Hinrichs, S. H., & Benedict, W. F. (1987). Structural evidence for the authenticity of the human retinoblastoma gene. Science (New York, N.Y.), 236(4809), 1657–1661.
Gérard, M., Morin, G., Bourillon, A., Colson, C., Mathieu, S., Rabier, D., … Benoist, J. F. (2015a). Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder. European Journal of Medical Genetics, 58(3), 148–153. http://doi.org/10.1016/j.ejmg.2014.12.015
Gérard, M., Morin, G., Bourillon, A., Colson, C., Mathieu, S., Rabier, D., … Benoist, J. F. (2015b). Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder. European Journal of Medical Genetics, 58(3), 148–153. http://doi.org/10.1016/j.ejmg.2014.12.015
Gerety, S. S., & Wilkinson, D. G. (2011). Morpholino artifacts provide pitfalls and reveal a novel role for pro-apoptotic genes in hindbrain boundary development. Developmental Biology, 350(2), 279–289. http://doi.org/10.1016/j.ydbio.2010.11.030
Guo, C., Chang, C.-C., Wortham, M., Chen, L. H., Kernagis, D. N., Qin, X., … He, Y. (2012). Global identification of MLL2-targeted loci reveals MLL2’s role in diverse signaling pathways. Proceedings of the National Academy of Sciences of the United States of America, 109(43), 17603–17608. http://doi.org/10.1073/pnas.1208807109
Hannibal, L., Kim, J., Brasch, N. E., Wang, S., Rosenblatt, D. S., Banerjee, R., & Jacobsen, D. W. (2009). Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product. Molecular Genetics and Metabolism, 97(4), 260–266.
http://doi.org/10.1016/j.ymgme.2009.04.005
Hehir-Kwa, J. Y., Pfundt, R., & Veltman, J. A. (2015). Exome sequencing and whole genome sequencing for the detection of copy number variation. Expert Review of Molecular Diagnostics, 1–10. http://doi.org/10.1586/14737159.2015.1053467
Henikoff, S., Till, B. J., & Comai, L. (2004). TILLING. Traditional mutagenesis meets functional genomics. Plant Physiology, 135(2), 630–636. http://doi.org/10.1104/pp.104.041061
Hines, J. H., Ravanelli, A. M., Schwindt, R., Scott, E. K., & Appel, B. (2015). Neuronal activity biases axon selection for myelination in vivo. Nature Neuroscience, 18(5), 683–689. http://doi.org/10.1038/nn.3992
Houdebine, L. M., & Chourrout, D. (1991). Transgenesis in fish. Experientia, 47(9), 891–897.
Howe, K., Clark, M. D., Torroja, C. F., Torrance, J., Berthelot, C., Muffato, M., … Stemple, D. L. (2013). The zebrafish reference genome sequence and its relationship to the human genome. Nature, 496(7446), 498–503. http://doi.org/10.1038/nature12111
Huang, L., Jolly, L. A., Willis-Owen, S., Gardner, A., Kumar, R., Douglas, E., … Gecz, J. (2012). A Noncoding, Regulatory Mutation Implicates HCFC1 in Nonsyndromic Intellectual Disability. American Journal of Human Genetics, 91(4), 694–702. http://doi.org/10.1016/j.ajhg.2012.08.011
Hwang, W. Y., Fu, Y., Reyon, D., Gonzales, A. P. W., Joung, J. K., & Yeh, J.-R. J. (2015). Targeted Mutagenesis in Zebrafish Using CRISPR RNA-Guided Nucleases. Methods in Molecular Biology (Clifton, N.J.), 1311, 317–334. http://doi.org/10.1007/978-1-4939-2687-9_21
Hwang, W. Y., Fu, Y., Reyon, D., Maeder, M. L., Tsai, S. Q., Sander, J. D., … Joung, J. K. (2013). Efficient genome editing in zebrafish using a CRISPR-Cas system. Nature Biotechnology, 31(3), 227–229. http://doi.org/10.1038/nbt.2501
Insights from human/mouse genome comparisons - art%3A10.1007%2Fs00335-002-4001-1.pdf. (n.d.). Retrieved August 24, 2015, from http://download.springer.com/static/pdf/244/art%253A10.1007%252Fs00335-002-4001-1.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs00335-002-4001-1&token2=exp=1440449210~acl=%2Fstatic%2Fpdf%2F244%2Fart%25253A10.1007%25252Fs00335-002-4001-1.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs00335-002-4001-1*~hmac=c9c2c701c8bfdf12588b6f783c8bc36e6a85fe7b8ff545e44c1d474c8b308d14
Je, E. M., Lee, S. H., Yoo, N. J., & Lee, S. H. (2013). Mutational and expressional analysis of MLL genes in gastric and colorectal cancers with microsatellite instability. Neoplasma, 60(2), 188–195.
Johansen Taber, K. A., Dickinson, B. D., & Wilson, M. (2014). The promise and challenges of next-generation genome sequencing for clinical care. JAMA Internal Medicine, 174(2), 275–280. http://doi.org/10.1001/jamainternmed.2013.12048
Jolly, L. A., Nguyen, L. S., Domingo, D., Sun, Y., Barry, S., Hancarova, M., … Gecz, J. (2015). HCFC1 loss-of-function mutations disrupt neuronal and neural progenitor cells of the developing brain. Human Molecular Genetics. http://doi.org/10.1093/hmg/ddv083
Kalueff, A. V., Stewart, A. M., & Gerlai, R. (2014). Zebrafish as an emerging model for studying complex brain disorders. Trends in Pharmacological Sciences, 35(2), 63–75. http://doi.org/10.1016/j.tips.2013.12.002
Karki, R., Pandya, D., Elston, R. C., & Ferlini, C. (2015). Defining “mutation” and “polymorphism” in the era of personal genomics. BMC Medical Genomics, 8, 37. http://doi.org/10.1186/s12920-015-0115-z
Kawakami, K. (2005). Transposon tools and methods in zebrafish. Developmental Dynamics: An Official Publication of the American Association of Anatomists, 234(2), 244–254. http://doi.org/10.1002/dvdy.20516
Kerem, B., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., … Tsui, L. C. (1989). Identification of the cystic fibrosis gene: genetic analysis. Science (New York, N.Y.), 245(4922), 1073–1080.
Kirby, B. B., Takada, N., Latimer, A. J., Shin, J., Carney, T. J., Kelsh, R. N., & Appel, B. (2006). In vivo time-lapse imaging shows dynamic oligodendrocyte progenitor behavior during zebrafish development. Nature Neuroscience, 9(12), 1506–1511. http://doi.org/10.1038/nn1803
Kwan, K. M., Fujimoto, E., Grabher, C., Mangum, B. D., Hardy, M. E., Campbell, D. S., … Chien, C.-B. (2007). The Tol2kit: a multisite gateway-based construction kit for Tol2 transposon transgenesis constructs. Developmental Dynamics: An Official Publication of the American Association of Anatomists, 236(11), 3088–3099. http://doi.org/10.1002/dvdy.21343
Lan, F., Bayliss, P. E., Rinn, J. L., Whetstine, J. R., Wang, J. K., Chen, S., … Shi, Y. (2007). A histone H3 lysine 27 demethylase regulates animal posterior development. Nature, 449(7163), 689–694. http://doi.org/10.1038/nature06192
Lederer, D., Grisart, B., Digilio, M. C., Benoit, V., Crespin, M., Ghariani, S. C., … Verellen-Dumoulin, C. (2012). Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. American Journal of Human Genetics, 90(1), 119–124. http://doi.org/10.1016/j.ajhg.2011.11.021
Lee, H., Deignan, J. L., Dorrani, N., Strom, S. P., Kantarci, S., Quintero-Rivera, F., … Nelson, S. F. (2014). Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA, 312(18), 1880–1887. http://doi.org/10.1001/jama.2014.14604
Leong, I. U. S., Lai, D., Lan, C.-C., Johnson, R., Love, D. R., Johnson, R., & Love, D. R. (2011). Targeted mutagenesis of zebrafish: use of zinc finger nucleases. Birth Defects Research. Part C, Embryo Today: Reviews, 93(3), 249–255. http://doi.org/10.1002/bdrc.20213
Lindgren, A. M., Hoyos, T., Talkowski, M. E., Hanscom, C., Blumenthal, I., Chiang, C., … Morton, C. C. (2013). Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate. Human Genetics, 132(5), 537–552. http://doi.org/10.1007/s00439-013-1263-x
Lin, L., Bolund, L., & Luo, Y. (2015). Towards personalized regenerative cell therapy: Mesenchymal stem cells derived from human induced pluripotent stem cells. Current Stem Cell Research & Therapy.
Liu, M.-Y., Yang, Y.-L., Chang, Y.-C., Chiang, S.-H., Lin, S.-P., Han, L.-S., … Liu, T.-T. (2010). Mutation spectrum of MMACHC in Chinese patients with combined methylmalonic aciduria and homocystinuria. Journal of Human Genetics, 55(9), 621–626. http://doi.org/10.1038/jhg.2010.81
Li, Y., Bögershausen, N., Alanay, Y., Simsek Kiper, P. O., Plume, N., Keupp, K., … Wollnik, B. (2011). A mutation screen in patients with Kabuki syndrome. Human Genetics, 130(6), 715–724. http://doi.org/10.1007/s00439-011-1004-y
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., … Church, G. M. (2013). RNA-guided human genome engineering via Cas9. Science (New York, N.Y.), 339(6121), 823–826. http://doi.org/10.1126/science.1232033
Martin, C., & Zhang, Y. (2005). The diverse functions of histone lysine methylation. Nature Reviews Molecular Cell Biology, 6(11), 838–849. http://doi.org/10.1038/nrm1761
Mathews, E. S., Mawdsley, D. J., Walker, M., Hines, J. H., Pozzoli, M., & Appel, B. (2014). Mutation of 3-hydroxy-3-methylglutaryl CoA synthase I reveals requirements for isoprenoid and cholesterol synthesis in oligodendrocyte migration arrest, axon wrapping, and myelin gene expression. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 34(9), 3402–3412. http://doi.org/10.1523/JNEUROSCI.4587-13.2014
Melvin, V. S., Feng, W., Hernandez-Lagunas, L., Artinger, K. B., & Williams, T. (2013). A morpholino-based screen to identify novel genes involved in craniofacial morphogenesis. Developmental Dynamics: An Official Publication of the American Association of Anatomists, 242(7), 817–831. http://doi.org/10.1002/dvdy.23969
Michaud, J., Praz, V., Faresse, N. J., Jnbaptiste, C. K., Tyagi, S., Schütz, F., & Herr, W. (2013). HCFC1 is a common component of active human CpG-island promoters and coincides with ZNF143, THAP11, YY1, and GABP transcription factor occupancy. Genome Research. http://doi.org/10.1101/gr.150078.112
Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P. A., Harshman, K., Tavtigian, S., … Ding, W. (1994). A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science (New York, N.Y.), 266(5182), 66–71.
Miyake, N., Koshimizu, E., Okamoto, N., Mizuno, S., Ogata, T., Nagai, T., … Niikawa, N. (2013). MLL2 and KDM6A mutations in patients with Kabuki syndrome. American Journal of Medical Genetics. Part A, 161A(9), 2234–2243. http://doi.org/10.1002/ajmg.a.36072
Moens, C. B., Donn, T. M., Wolf-Saxon, E. R., & Ma, T. P. (2008). Reverse genetics in zebrafish by TILLING. Briefings in Functional Genomics & Proteomics, 7(6), 454–459. http://doi.org/10.1093/bfgp/eln046
Moscou, M. J., & Bogdanove, A. J. (2009). A simple cipher governs DNA recognition by TAL effectors. Science (New York, N.Y.), 326(5959), 1501. http://doi.org/10.1126/science.1178817
Mouse Genome Sequencing Consortium, Waterston, R. H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J. F., … Lander, E. S. (2002). Initial sequencing and comparative analysis of the mouse genome. Nature, 420(6915), 520–562. http://doi.org/10.1038/nature01262
Natarajan, T. G., Kallakury, B. V., Sheehan, C. E., Bartlett, M. B., Ganesan, N., Preet, A., … Fitzgerald, K. T. (2010). Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon. Cancer Cell International, 10, 13. http://doi.org/10.1186/1475-2867-10-13
Ng, S. B., Bigham, A. W., Buckingham, K. J., Hannibal, M. C., McMillin, M. J., Gildersleeve, H. I., … Shendure, J. (2010). Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nature Genetics, 42(9), 790–793. http://doi.org/10.1038/ng.646
Ng, S. B., Buckingham, K. J., Lee, C., Bigham, A. W., Tabor, H. K., Dent, K. M., … Bamshad, M. J. (2010). Exome sequencing identifies the cause of a mendelian disorder. Nature Genetics, 42(1), 30–35. http://doi.org/10.1038/ng.499
Niikawa, N., Matsuura, N., Fukushima, Y., Ohsawa, T., & Kajii, T. (1981). Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. The Journal of Pediatrics, 99(4), 565–569.
Ooki, S. (2012). Multiple Congenital Anomalies after Assisted Reproductive Technology in Japan (between 2004 and 2009). International Scholarly Research Notices, 2013, e452085. http://doi.org/10.5402/2013/452085
Pelegri, F. J. (Ed.). (2011). Inducing High Rates of Targeted Mutagenesis in Zebrafish Using Zinc Finger Nucleases (ZFNs) - Springer. Humana Press. Retrieved from http://link.springer.com/protocol/10.1007%2F978-1-61779-210-6_20
Quintana, A. M., Geiger, E. A., Achilly, N., Rosenblatt, D. S., Maclean, K. N., Stabler, S. P., … Shaikh, T. H. (2014). Hcfc1b, a zebrafish ortholog of HCFC1, regulates craniofacial development by modulating mmachc expression. Developmental Biology, 396(1), 94–106. http://doi.org/10.1016/j.ydbio.2014.09.026
Rabbani, B., Mahdieh, N., Hosomichi, K., Nakaoka, H., & Inoue, I. (2012). Next-generation sequencing: impact of exome sequencing in characterizing Mendelian disorders. Journal of Human Genetics, 57(10), 621–632. http://doi.org/10.1038/jhg.2012.91
Rabello, D. do A., de Moura, C. A., de Andrade, R. V., Motoyama, A. B., & Silva, F. P. (2013). Altered expression of MLL methyltransferase family genes in breast cancer. International Journal of Oncology, 43(2), 653–660. http://doi.org/10.3892/ijo.2013.1981
Sams-Dodd, F. (2005). Target-based drug discovery: is something wrong? Drug Discovery Today, 10(2), 139–147. http://doi.org/10.1016/S1359-6446(04)03316-1
Sanderson, L. E., Chien, A.-T., Astin, J. W., Crosier, K. E., Crosier, P. S., & Hall, C. J. (2015). An inducible transgene reports activation of macrophages in live zebrafish larvae. Developmental and Comparative Immunology, 53(1), 63–69. http://doi.org/10.1016/j.dci.2015.06.013
Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., … Shiloh, Y. (1995). A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science (New York, N.Y.), 268(5218), 1749–1753.
Ségalat, L. (2007). Invertebrate animal models of diseases as screening tools in drug discovery. ACS Chemical Biology, 2(4), 231–236. http://doi.org/10.1021/cb700009m
Shimizu, T., & Nakagawa, K. (2015). [Novel signal transduction pathways: the molecular basis for targeted cancer therapies in Hedgehog/Notch/Wnt pathway]. Nihon Rinsho. Japanese Journal of Clinical Medicine, 73(8), 1342–1348.
Simpson, M. A., Irving, M. D., Asilmaz, E., Gray, M. J., Dafou, D., Elmslie, F. V., … Trembath, R. C. (2011). Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nature Genetics, 43(4), 303–305. http://doi.org/10.1038/ng.779
Smith, E., Lin, C., & Shilatifard, A. (2011). The super elongation complex (SEC) and MLL in development and disease. Genes & Development, 25(7), 661–672. http://doi.org/10.1101/gad.2015411
Snyder, J. L., Kearns, C. A., & Appel, B. (2012). Fbxw7 regulates Notch to control specification of neural precursors for oligodendrocyte fate. Neural Development, 7, 15. http://doi.org/10.1186/1749-8104-7-15
Summerton, J. E. (2007). Morpholino, siRNA, and S-DNA compared: impact of structure and mechanism of action on off-target effects and sequence specificity. Current Topics in Medicinal Chemistry, 7(7), 651–660.
Sun, N., & Zhao, H. (2013). Transcription activator-like effector nucleases (TALENs): a highly efficient and versatile tool for genome editing. Biotechnology and Bioengineering, 110(7), 1811–1821. http://doi.org/10.1002/bit.24890
Suster, M. L., Kikuta, H., Urasaki, A., Asakawa, K., & Kawakami, K. (2009). Transgenesis in zebrafish with the tol2 transposon system. Methods in Molecular Biology (Clifton, N.J.), 561, 41–63. http://doi.org/10.1007/978-1-60327-019-9_3
Taylor, E. W., Xu, J., Jabs, E. W., & Meyers, D. A. (1997). Linkage analysis of genetic disorders. Methods in Molecular Biology (Clifton, N.J.), 68, 11–25.
Taylor, J. S., Van de Peer, Y., Braasch, I., & Meyer, A. (2001). Comparative genomics provides evidence for an ancient genome duplication event in fish. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 356(1414), 1661–1679. http://doi.org/10.1098/rstb.2001.0975
Tzur, Y. B., Friedland, A. E., Nadarajan, S., Church, G. M., Calarco, J. A., & Colaiácovo, M. P. (2013). Heritable custom genomic modifications in Caenorhabditis elegans via a CRISPR-Cas9 system. Genetics, 195(3), 1181–1185. http://doi.org/10.1534/genetics.113.156075
Vandenbergh, J. G. (2000). Use of House Mice in Biomedical Research. ILAR Journal, 41(3), 133–135. http://doi.org/10.1093/ilar.41.3.133
Van Laarhoven, P. M., Neitzel, L. R., Quintana, A. M., Geiger, E. A., Zackai, E. H., Clouthier, D. E., … Shaikh, T. H. (2015). Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development. Human Molecular Genetics. http://doi.org/10.1093/hmg/ddv180
Weisfeld-Adams, J. D., Bender, H. A., Miley-Åkerstedt, A., Frempong, T., Schrager, N. L., Patel, K., … Diaz, G. A. (2013). Neurologic and neurodevelopmental phenotypes in young children with early-treated combined methylmalonic acidemia and homocystinuria, cobalamin C type. Molecular Genetics and Metabolism, 110(3), 241–247. http://doi.org/10.1016/j.ymgme.2013.07.018
Welte, Y., Davies, C., Schäfer, R., & Regenbrecht, C. R. A. (2013). Patient derived cell culture and isolation of CD133+ putative cancer stem cells from melanoma. Journal of Visualized Experiments: JoVE, (73), e50200. http://doi.org/10.3791/50200
Winkler, S., Gscheidel, N., & Brand, M. (2011). Mutant generation in vertebrate model organisms by TILLING. Methods in Molecular Biology (Clifton, N.J.), 770, 475–504. http://doi.org/10.1007/978-1-61779-210-6_19
Yin, L., Jao, L.-E., & Chen, W. (2015). Generation of Targeted Mutations in Zebrafish Using the CRISPR/Cas System. Methods in Molecular Biology (Clifton, N.J.), 1332, 205–217. http://doi.org/10.1007/978-1-4939-2917-7_16
Yin, S., Yang, J., Lin, B., Deng, W., Zhang, Y., Yi, X., … Kong, X. (2014). Exome sequencing identifies frequent mutation of MLL2 in non-small cell lung carcinoma from Chinese patients. Scientific Reports, 4, 6036. http://doi.org/10.1038/srep06036
Yuan, X., Wu, H., Xu, H., Xiong, H., Chu, Q., Yu, S., … Wu, K. (2015). Notch signaling: An emerging therapeutic target for cancer treatment. Cancer Letters. http://doi.org/10.1016/j.canlet.2015.07.048
Yu, H.-C., Geiger, E. A., Medne, L., Zackai, E. H., & Shaikh, T. H. (2014). An individual with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and additional features expands the phenotype associated with mutations in KAT6B. American Journal of Medical Genetics. Part A. http://doi.org/10.1002/ajmg.a.36379
Yu, H.-C., Sloan, J. L., Scharer, G., Brebner, A., Quintana, A. M., Achilly, N. P., … Shaikh, T. H. (2013). An X-Linked Cobalamin Disorder Caused by Mutations in Transcriptional Coregulator HCFC1. American Journal of Human Genetics, 93(3), 506–514. http://doi.org/10.1016/j.ajhg.2013.07.022
Zhang, X. (2014). Exome sequencing greatly expedites the progressive research of Mendelian diseases. Frontiers of Medicine, 8(1), 42–57. http://doi.org/10.1007/s11684-014-0303-9