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September 2020

Dorsal surface and block face micrographs of unaffected (left), Zfp423-hypomorphic (middle), and Zfp423-null (right) mutant brains show sensitivity of midline structures to reduced Zfp423 function. Brain development requires coordination among cell lineage and extracellular signaling information. Zfp423's zinc finger domains bind DNA and other regulatory proteins in lineage- and signal-dependent contexts, including EBF, SMAD, retinoic acid receptor, notch intracellular domain, and DNA damage response proteins. Simple structural measures are sensitive to even heterozygous loss of Zfp423, allowing rapid phenotyping of variants. Among reported patient amino acid substitution variants, however, only H1277Y, which disrupts an EBF-binding zinc finger, shows an effect. See Deshpande et al.

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Image Credit: Ojas Deshpande

Research Articles

A mega-analysis of expression quantitative trait loci in retinal tissue

Tobias Strunz, Christina Kiel, Felix Grassmann, Rinki Ratnapriya, Madeline Kwicklis, Marcus Karlstetter, Sascha Fauser, Nicole Arend, Anand Swaroop, Thomas Langmann, Armin Wolf, Bernhard H. F. Weber

Trappc9 deficiency causes parent-of-origin dependent microcephaly and obesity

Zhengzheng S. Liang, Irene Cimino, Binnaz Yalcin, Narayanan Raghupathy, Valerie E. Vancollie, Ximena Ibarra-Soria, Helen V. Firth, Debra Rimmington, I. Sadaf Farooqi, Christopher J. Lelliott, Steven C. Munger, Stephen O’Rahilly, Anne C. Ferguson-Smith, Anthony P. Coll, Darren W. Logan

Trichoderma reesei XYR1 activates cellulase gene expression via interaction with the Mediator subunit TrGAL11 to recruit RNA polymerase II

Fanglin Zheng, Yanli Cao, Renfei Yang, Lei Wang, Xinxing Lv, Weixin Zhang, Xiangfeng Meng, Weifeng Liu

Excess crossovers impede faithful meiotic chromosome segregation in C. elegans

Jeremy A. Hollis, Marissa L. Glover, Aleesa J. Schlientz, Cori K. Cahoon, Bruce Bowerman, Sarah M. Wignall, Diana E. Libuda

Male-biased aganglionic megacolon in the TashT mouse model of Hirschsprung disease involves upregulation of p53 protein activity and Ddx3y gene expression

Tatiana Cardinal, Karl-Frédérik Bergeron, Rodolphe Soret, Ouliana Souchkova, Christophe Faure, Amélina Guillon, Nicolas Pilon

Genetic analysis of the modern Australian labradoodle dog breed reveals an excess of the poodle genome

Muhammad Basil Ali, Jacquelyn M. Evans, Heidi G. Parker, Jaemin Kim, Susan Pearce-Kelling, D. Thad Whitaker, Jocelyn Plassais, Qaiser M. Khan, Elaine A. Ostrander

Adiponectin GWAS loci harboring extensive allelic heterogeneity exhibit distinct molecular consequences

Cassandra N. Spracklen, Apoorva K. Iyengar, Swarooparani Vadlamudi, Chelsea K. Raulerson, Anne U. Jackson, Sarah M. Brotman, Ying Wu, Maren E. Cannon, James P. Davis, Aaron T. Crain, Kevin W. Currin, Hannah J. Perrin, Narisu Narisu, Heather M. Stringham, Christian Fuchsberger, Adam E. Locke, Ryan P. Welch, Johanna K. Kuusisto, Päivi Pajukanta, Laura J. Scott, Yun Li, Francis S. Collins, Michael Boehnke, Markku Laakso, Karen L. Mohlke

Using prior information from humans to prioritize genes and gene-associated variants for complex traits in livestock

Biaty Raymond, Loic Yengo, Roy Costilla, Chris Schrooten, Aniek C. Bouwman, Ben J. Hayes, Roel F. Veerkamp, Peter M. Visscher

ZNF423 patient variants, truncations, and in-frame deletions in mice define an allele-dependent range of midline brain abnormalities

Ojas Deshpande, Raquel Z. Lara, Oliver R. Zhang, Dorothy Concepcion, Bruce A. Hamilton

The causal effect of obesity on prediabetes and insulin resistance reveals the important role of adipose tissue in insulin resistance

Zong Miao, Marcus Alvarez, Arthur Ko, Yash Bhagat, Elior Rahmani, Brandon Jew, Sini Heinonen, Linda Liliana Muñoz-Hernandez, Miguel Herrera-Hernandez, Carlos Aguilar-Salinas, Teresa Tusie-Luna, Karen L. Mohlke, Markku Laakso, Kirsi H. Pietiläinen, Eran Halperin, Päivi Pajukanta

The Arabidopsis PHD-finger protein EDM2 has multiple roles in balancing NLR immune receptor gene expression

Yan Lai, Xueqing Maggie Lu, Josquin Daron, Songqin Pan, Jianqiang Wang, Wei Wang, Tokuji Tsuchiya, Eric Holub, John M. McDowell, R. Keith Slotkin, Karine G. Le Roch, Thomas Eulgem

A Novel Recessive Mutation in SPEG Causes Early Onset Dilated Cardiomyopathy

Aviva Levitas, Emad Muhammad, Yuan Zhang, Isaac Perea Gil, Ricardo Serrano, Nashielli Diaz, Maram Arafat, Alexandra A. Gavidia, Michael S. Kapiloff, Mark Mercola, Yoram Etzion, Ruti Parvari, Ioannis Karakikes

TENET 2.0: Identification of key transcriptional regulators and enhancers in lung adenocarcinoma

Daniel J. Mullen, Chunli Yan, Diane S. Kang, Beiyun Zhou, Zea Borok, Crystal N. Marconett, Peggy J. Farnham, Ite A. Offringa, Suhn Kyong Rhie

Meiotic cohesins mediate initial loading of HORMAD1 to the chromosomes and coordinate SC formation during meiotic prophase

Yasuhiro Fujiwara, Yuki Horisawa-Takada, Erina Inoue, Naoki Tani, Hiroki Shibuya, Sayoko Fujimura, Ryo Kariyazono, Toyonori Sakata, Kunihiro Ohta, Kimi Araki, Yuki Okada, Kei-ichiro Ishiguro

PIG-1 MELK-dependent phosphorylation of nonmuscle myosin II promotes apoptosis through CES-1 Snail partitioning

Hai Wei, Eric J. Lambie, Daniel S. Osório, Ana X. Carvalho, Barbara Conradt

Leveraging correlations between variants in polygenic risk scores to detect heterogeneity in GWAS cohorts

Jie Yuan, Henry Xing, Alexandre Louis Lamy, The Schizophrenia Working Group of the Psychiatric Genomics Consortium, Todd Lencz, Itsik Pe’er

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