%0 Journal Article %J Am J Hum Genet %D 2014 %T Monoallelic and biallelic mutations in MAB21L2 cause a spectrum of major eye malformations. %A Rainger, Joe %A Pehlivan, Davut %A Johansson, Stefan %A Bengani, Hemant %A Sanchez-Pulido, Luis %A Williamson, Kathleen A %A Ture, Mehmet %A Barker, Heather %A Rosendahl, Karen %A Spranger, Jürgen %A Horn, Denise %A Meynert, Alison %A Floyd, James A B %A Prescott, Trine %A Anderson, Carl A %A Rainger, Jacqueline K %A Karaca, Ender %A Gonzaga-Jauregui, Claudia %A Jhangiani, Shalini %A Muzny, Donna M %A Seawright, Anne %A Soares, Dinesh C %A Kharbanda, Mira %A Murday, Victoria %A Finch, Andrew %A Gibbs, Richard A %A van Heyningen, Veronica %A Taylor, Martin S %A Yakut, Tahsin %A Knappskog, Per M %A Hurles, Matthew E %A Ponting, Chris P %A Lupski, James R %A Houge, Gunnar %A FitzPatrick, David R %K Adult %K Alleles %K Animals %K Anophthalmos %K Brain Diseases, Metabolic, Inborn %K Coloboma %K Corneal Opacity %K Exome %K Eye Proteins %K Female %K Gene Expression %K HEK293 Cells %K Heterozygote %K Homozygote %K Humans %K Intellectual Disability %K Intracellular Signaling Peptides and Proteins %K Male %K Mice %K Microcephaly %K Microphthalmos %K Mutation, Missense %K Pedigree %K Phenotype %K Protein Conformation %K Signal Transduction %X

We identified four different missense mutations in the single-exon gene MAB21L2 in eight individuals with bilateral eye malformations from five unrelated families via three independent exome sequencing projects. Three mutational events altered the same amino acid (Arg51), and two were identical de novo mutations (c.151C>T [p.Arg51Cys]) in unrelated children with bilateral anophthalmia, intellectual disability, and rhizomelic skeletal dysplasia. c.152G>A (p.Arg51His) segregated with autosomal-dominant bilateral colobomatous microphthalmia in a large multiplex family. The fourth heterozygous mutation (c.145G>A [p.Glu49Lys]) affected an amino acid within two residues of Arg51 in an adult male with bilateral colobomata. In a fifth family, a homozygous mutation (c.740G>A [p.Arg247Gln]) altering a different region of the protein was identified in two male siblings with bilateral retinal colobomata. In mouse embryos, Mab21l2 showed strong expression in the developing eye, pharyngeal arches, and limb bud. As predicted by structural homology, wild-type MAB21L2 bound single-stranded RNA, whereas this activity was lost in all altered forms of the protein. MAB21L2 had no detectable nucleotidyltransferase activity in vitro, and its function remains unknown. Induced expression of wild-type MAB21L2 in human embryonic kidney 293 cells increased phospho-ERK (pERK1/2) signaling. Compared to the wild-type and p.Arg247Gln proteins, the proteins with the Glu49 and Arg51 variants had increased stability. Abnormal persistence of pERK1/2 signaling in MAB21L2-expressing cells during development is a plausible pathogenic mechanism for the heterozygous mutations. The phenotype associated with the homozygous mutation might be a consequence of complete loss of MAB21L2 RNA binding, although the cellular function of this interaction remains unknown.

%B Am J Hum Genet %V 94 %P 915-23 %8 2014 Jun 05 %G eng %N 6 %1 https://www.ncbi.nlm.nih.gov/pubmed/24906020?dopt=Abstract %R 10.1016/j.ajhg.2014.05.005 %0 Journal Article %J Nature %D 2004 %T Genome sequence of the Brown Norway rat yields insights into mammalian evolution. %A Gibbs, Richard A %A Weinstock, George M %A Metzker, Michael L %A Muzny, Donna M %A Sodergren, Erica J %A Scherer, Steven %A Scott, Graham %A Steffen, David %A Worley, Kim C %A Burch, Paula E %A Okwuonu, Geoffrey %A Hines, Sandra %A Lewis, Lora %A DeRamo, Christine %A Delgado, Oliver %A Dugan-Rocha, Shannon %A Miner, George %A Morgan, Margaret %A Hawes, Alicia %A Gill, Rachel %A Holt, Robert A %A Adams, Mark D %A Amanatides, Peter G %A Baden-Tillson, Holly %A Barnstead, Mary %A Chin, Soo %A Evans, Cheryl A %A Ferriera, Steve %A Fosler, Carl %A Glodek, Anna %A Gu, Zhiping %A Jennings, Don %A Kraft, Cheryl L %A Nguyen, Trixie %A Pfannkoch, Cynthia M %A Sitter, Cynthia %A Sutton, Granger G %A Venter, J Craig %A Woodage, Trevor %A Smith, Douglas %A Lee, Hong-Mei %A Gustafson, Erik %A Cahill, Patrick %A Kana, Arnold %A Doucette-Stamm, Lynn %A Weinstock, Keith %A Fechtel, Kim %A Weiss, Robert B %A Dunn, Diane M %A Green, Eric D %A Blakesley, Robert W %A Bouffard, Gerard G %A De Jong, Pieter J %A Osoegawa, Kazutoyo %A Zhu, Baoli %A Marra, Marco %A Schein, Jacqueline %A Bosdet, Ian %A Fjell, Chris %A Jones, Steven %A Krzywinski, Martin %A Mathewson, Carrie %A Siddiqui, Asim %A Wye, Natasja %A McPherson, John %A Zhao, Shaying %A Fraser, Claire M %A Shetty, Jyoti %A Shatsman, Sofiya %A Geer, Keita %A Chen, Yixin %A Abramzon, Sofyia %A Nierman, William C %A Havlak, Paul H %A Chen, Rui %A Durbin, K James %A Simons, Rain %A Ren, Yanru %A Song, Xing-Zhi %A Li, Bingshan %A Liu, Yue %A Qin, Xiang %A Cawley, Simon %A Worley, Kim C %A Cooney, A J %A D'Souza, Lisa M %A Martin, Kirt %A Wu, Jia Qian %A Gonzalez-Garay, Manuel L %A Jackson, Andrew R %A Kalafus, Kenneth J %A McLeod, Michael P %A Milosavljevic, Aleksandar %A Virk, Davinder %A Volkov, Andrei %A Wheeler, David A %A Zhang, Zhengdong %A Bailey, Jeffrey A %A Eichler, Evan E %A Tuzun, Eray %A Birney, Ewan %A Mongin, Emmanuel %A Ureta-Vidal, Abel %A Woodwark, Cara %A Zdobnov, Evgeny %A Bork, Peer %A Suyama, Mikita %A Torrents, David %A Alexandersson, Marina %A Trask, Barbara J %A Young, Janet M %A Huang, Hui %A Wang, Huajun %A Xing, Heming %A Daniels, Sue %A Gietzen, Darryl %A Schmidt, Jeanette %A Stevens, Kristian %A Vitt, Ursula %A Wingrove, Jim %A Camara, Francisco %A Mar Albà, M %A Abril, Josep F %A Guigó, Roderic %A Smit, Arian %A Dubchak, Inna %A Rubin, Edward M %A Couronne, Olivier %A Poliakov, Alexander %A Hübner, Norbert %A Ganten, Detlev %A Goesele, Claudia %A Hummel, Oliver %A Kreitler, Thomas %A Lee, Young-Ae %A Monti, Jan %A Schulz, Herbert %A Zimdahl, Heike %A Himmelbauer, Heinz %A Lehrach, Hans %A Jacob, Howard J %A Bromberg, Susan %A Gullings-Handley, Jo %A Jensen-Seaman, Michael I %A Kwitek, Anne E %A Lazar, Jozef %A Pasko, Dean %A Tonellato, Peter J %A Twigger, Simon %A Ponting, Chris P %A Duarte, Jose M %A Rice, Stephen %A Goodstadt, Leo %A Beatson, Scott A %A Emes, Richard D %A Winter, Eitan E %A Webber, Caleb %A Brandt, Petra %A Nyakatura, Gerald %A Adetobi, Margaret %A Chiaromonte, Francesca %A Elnitski, Laura %A Eswara, Pallavi %A Hardison, Ross C %A Hou, Minmei %A Kolbe, Diana %A Makova, Kateryna %A Miller, Webb %A Nekrutenko, Anton %A Riemer, Cathy %A Schwartz, Scott %A Taylor, James %A Yang, Shan %A Zhang, Yi %A Lindpaintner, Klaus %A Andrews, T Dan %A Caccamo, Mario %A Clamp, Michele %A Clarke, Laura %A Curwen, Valerie %A Durbin, Richard %A Eyras, Eduardo %A Searle, Stephen M %A Cooper, Gregory M %A Batzoglou, Serafim %A Brudno, Michael %A Sidow, Arend %A Stone, Eric A %A Venter, J Craig %A Payseur, Bret A %A Bourque, Guillaume %A López-Otín, Carlos %A Puente, Xose S %A Chakrabarti, Kushal %A Chatterji, Sourav %A Dewey, Colin %A Pachter, Lior %A Bray, Nicolas %A Yap, Von Bing %A Caspi, Anat %A Tesler, Glenn %A Pevzner, Pavel A %A Haussler, David %A Roskin, Krishna M %A Baertsch, Robert %A Clawson, Hiram %A Furey, Terrence S %A Hinrichs, Angie S %A Karolchik, Donna %A Kent, William J %A Rosenbloom, Kate R %A Trumbower, Heather %A Weirauch, Matt %A Cooper, David N %A Stenson, Peter D %A Ma, Bin %A Brent, Michael %A Arumugam, Manimozhiyan %A Shteynberg, David %A Copley, Richard R %A Taylor, Martin S %A Riethman, Harold %A Mudunuri, Uma %A Peterson, Jane %A Guyer, Mark %A Felsenfeld, Adam %A Old, Susan %A Mockrin, Stephen %A Collins, Francis %K Animals %K Base Composition %K Centromere %K Chromosomes, Mammalian %K CpG Islands %K DNA Transposable Elements %K DNA, Mitochondrial %K Evolution, Molecular %K Gene Duplication %K Genome %K Genomics %K Humans %K Introns %K Male %K Mice %K Models, Molecular %K Mutagenesis %K Polymorphism, Single Nucleotide %K Rats %K Rats, Inbred BN %K Regulatory Sequences, Nucleic Acid %K Retroelements %K RNA Splice Sites %K RNA, Untranslated %K Sequence Analysis, DNA %K Telomere %X

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

%B Nature %V 428 %P 493-521 %8 2004 Apr 01 %G eng %N 6982 %1 https://www.ncbi.nlm.nih.gov/pubmed/15057822?dopt=Abstract %R 10.1038/nature02426