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The ring finger protein 213 gene ( Rnf213 ) contributes to Rift Valley fever resistance in mice Mamm. Genome (IF 2.287) Pub Date : 2021-01-09 Denis Houzelstein, Dominique Simon-Chazottes, Leandro Batista, Satoko Tokuda, Francina Langa Vives, Marie Flamand, Xavier Montagutelli, Jean-Jacques Panthier
Rift Valley fever (RVF) is an emerging viral zoonosis that primarily affects ruminants and humans. We have previously shown that wild-derived MBT/Pas mice are highly susceptible to RVF virus and that part of this phenotype is controlled by a locus located on distal Chromosome 11. Using congenic strains, we narrowed down the critical interval to a 530 kb region containing five protein-coding genes among
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Alopecia in Harlequin mutant mice is associated with reduced AIF protein levels and expression of retroviral elements Mamm. Genome (IF 2.287) Pub Date : 2020-12-26 Maik Hintze, Sebastian Griesing, Marion Michels, Birgit Blanck, Lena Wischhof, Dieter Hartmann, Daniele Bano, Thomas Franz
We investigated the contribution of apoptosis-inducing factor (AIF), a key regulator of mitochondrial biogenesis, in supporting hair growth. We report that pelage abnormalities developed during hair follicle (HF) morphogenesis in Harlequin (Hq) mutant mice. Fragility of the hair cortex was associated with decreased expression of genes encoding structural hair proteins, though key transcriptional regulators
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Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo Mamm. Genome (IF 2.287) Pub Date : 2020-11-28 Udita Upadhyay, Gerald Z. Zhuang, Luda Diatchenko, Marc Parisien, Yuan Kang, Konstantinos D. Sarantopoulos, Eden R. Martin, Shad B. Smith, William Maixner, Roy C. Levitt
Intracellular calcium is critical in orchestrating neuronal excitability and analgesia. Carbonic anhydrase-8 (CA8) regulates intracellular calcium signaling through allosteric inhibition of neuronal inositol trisphosphate receptor 1 (ITPR1) to produce profound analgesia. Recently, we reported the “G” allele at rs6471859 represents cis-eQTL regulating alternative splicing of a 1697 bp transcript (CA8-204G)
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Intramuscular injection of tetracycline decreased gut microbial diversity in mouse Mamm. Genome (IF 2.287) Pub Date : 2020-11-22 Jia Liu, Xi-chuan Deng, Xiao-yu Li, Zhi-bang Yang, Guang-yuan Zhang, Ting-ting Chen
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Differential protein input in the maternal diet alters the skeletal muscle transcriptome in fetal sheep Mamm. Genome (IF 2.287) Pub Date : 2020-11-07 Md Mahmodul Hasan Sohel, Bilal Akyuz, Yusuf Konca, Korhan Arslan, Kutlay Gurbulak, Murat Abay, Mahmut Kaliber, Mehmet Ulas Cinar
Maternal nutrition during pregnancy is one of the major intrauterine environmental factors that influence fetal development by significantly altering the expression of genes that might have a consequence on the physiological, morphological, and metabolic performance of the offspring in the postnatal period. The impact of maternal dietary protein on the expression of genes in sheep fetal skeletal muscle
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Derivation of stable embryonic stem cell-like, but transcriptionally heterogenous, induced pluripotent stem cells from non-permissive mouse strains Mamm. Genome (IF 2.287) Pub Date : 2020-10-04 Tiffany A. Garbutt, Kranti Konganti, Thomas Konneker, Andrew Hillhouse, Drake Phelps, Alexis Jones, David Aylor, David W. Threadgill
Genetic background is known to play a role in the ability to derive pluripotent, embryonic stem cells (ESC), a trait referred to as permissiveness. Previously we demonstrated that induced pluripotent stem cells (iPSC) can be readily derived from non-permissive mouse strains by addition of serum-based media supplemented with GSK3B and MEK inhibitors, termed 2iS media, 3 days into reprogramming. Here
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Baseline and innate immune response characterization of a Zfp30 knockout mouse strain. Mamm. Genome (IF 2.287) Pub Date : 2020-08-29 Lucas T Laudermilk,Adelaide Tovar,Alison K Homstad,Joseph M Thomas,Kathryn M McFadden,Miriya K Tune,Dale O Cowley,Jason R Mock,Folami Ideraabdullah,Samir N P Kelada
Airway neutrophilia is correlated with disease severity in a number of chronic and acute pulmonary diseases, and dysregulation of neutrophil chemotaxis can lead to host tissue damage. The gene Zfp30 was previously identified as a candidate regulator of neutrophil recruitment to the lungs and secretion of CXCL1, a potent neutrophil chemokine, in a genome-wide mapping study using the Collaborative Cross
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Nuclear factor NF-κB1 functional promoter polymorphism and its expression conferring the risk of Type 2 diabetes-associated dyslipidemia. Mamm. Genome (IF 2.287) Pub Date : 2020-08-26 Tanima Chatterjee,Debasmita De,Subhankar Chowdhury,Maitree Bhattacharyya
Type 2 diabetes mellitus (T2DM) accompanied by hyperlipidemia confers higher risk for diabetes as well as cardiovascular diseases. NF-κB is actively involved in generating low-grade inflammation and oxidative stress triggering the development of diabetic complications. In this study, we have attempted to investigate the association between NF-κB1 functional promoter polymorphism-94 ATTG insertion/deletion
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A scan for genes associated with cancer mortality and longevity in pedigree dog breeds. Mamm. Genome (IF 2.287) Pub Date : 2020-07-13 Aoife Doherty,Inês Lopes,Christopher T Ford,Gianni Monaco,Patrick Guest,João Pedro de Magalhães
Selective breeding of the domestic dog (Canis lupus familiaris) rigidly retains desirable features, and could inadvertently fix disease-causing variants within a breed. We combine phenotypic data from > 72,000 dogs with a large genotypic dataset to search for genes associated with cancer mortality and longevity in pedigree dog breeds. We validated previous findings that breeds with higher average body
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Diversification of CpG-Island Promoters Revealed by Comparative Analysis Between Human and Rhesus Monkey Genomes. Mamm. Genome (IF 2.287) Pub Date : 2020-07-09 Saki Aoto,Mayu Fushimi,Kei Yura,Kohji Okamura
While CpG dinucleotides are significantly reduced compared to other dinucleotides in mammalian genomes, they can congregate and form CpG islands, which localize around the 5ʹ regions of genes, where they function as promoters. CpG-island promoters are generally unmethylated and are often found in housekeeping genes. However, their nucleotide sequences and existence per se are not conserved between
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Eukaryotic translation initiation factor 3 subunit b is a novel oncogenic factor in prostate cancer. Mamm. Genome (IF 2.287) Pub Date : 2020-06-15 Ping Xiang,Youwen Sun,Zhiqing Fang,Keqiang Yan,Yidong Fan
Prostate cancer, the second most common cancer among male adults, affects millions globally. We sought to investigate the expression and contribution of Eukaryotic translation initiation factor 3 subunit b (EIF3B) in prostate cancer. Expression of EIF3B was analyzed in both human prostate patient tissues and prostate cancer cell lines. Small interfering RNA (siRNA) knockdown of EIF3B was introduced
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Genetic control of non-genetic inheritance in mammals: state-of-the-art and perspectives. Mamm. Genome (IF 2.287) Pub Date : 2020-06-11 A Tomar,R Teperino
Thought to be directly and uniquely dependent from genotypes, the ontogeny of individual phenotypes is much more complicated. Individual genetics, environmental exposures, and their interaction are the three main determinants of individual’s phenotype. This picture has been further complicated a decade ago when the Lamarckian theory of acquired inheritance has been rekindled with the discovery of epigenetic
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MALDI-TOF-MS-based high throughput genotyping of mutations associated with body measurement traits in cattle. Mamm. Genome (IF 2.287) Pub Date : 2020-05-08 Yongfeng Liu,Yang Jiao,Peiwei Li,Linsen Zan
Exploration of genes in relation to body measurement traits through large-scaled mutation identification is highly conductive for the genomics-assisted breeding of superior productivity cattle. In this investigation, 31 objective mutations were genotyped synchronously in 384 yellow cattle of 8 breeds through the application of optimized MALDI-TOF-MS and multiplex PCR techniques. High genotyping rate
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Nutrition and its role in epigenetic inheritance of obesity and diabetes across generations. Mamm. Genome (IF 2.287) Pub Date : 2020-04-30 Daniela Kaspar,Sieglinde Hastreiter,Martin Irmler,Martin Hrabé de Angelis,Johannes Beckers
Nutritional constraints including not only caloric restriction or protein deficiency, but also energy-dense diets affect metabolic health and frequently lead to obesity and insulin resistance, as well as glucose intolerance and type 2 diabetes. The effects of these environmental factors are often mediated via epigenetic modifiers that target the expression of metabolic genes. More recently, it was
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PKM2 ablation enhanced retinal function and survival in a preclinical model of retinitis pigmentosa. Mamm. Genome (IF 2.287) Pub Date : 2020-04-27 Ethan Zhang,Joseph Ryu,Sarah R Levi,Jin Kyun Oh,Chun Wei Hsu,Xuan Cui,Ting-Ting Lee,Nan-Kai Wang,Jose Ronaldo Lima de Carvalho,Stephen H Tsang
Retinitis pigmentosa (RP) is a neurodegenerative disorder that causes irreversible vision loss in over 1.5 million individuals world-wide. The genetic heterogeneity of RP necessitates a broad therapy that is able to provide treatment in a gene- and mutation- non-specific manner. In this study, we identify the therapeutic benefits of metabolic reprogramming by targeting pyruvate kinase M2 (PKM2) in
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Identification and comparison of the porcine H1, U6, and 7SK RNA polymerase III promoters for short hairpin RNA expression. Mamm. Genome (IF 2.287) Pub Date : 2020-04-21 Hai-Chang Yin,Xin-Yu Chen,Wei Wang,Qing-Wen Meng
RNA polymerase III is an essential enzyme in eukaryotes for synthesis of tRNA, 5S rRNA, and other small nuclear and cytoplasmic RNAs. Thus, RNA polymerase III promoters are often used in small hairpin RNA (shRNA) expression. In this study, the porcine H1, U6, and 7SK RNA polymerase III type promoters were cloned into a pcDNA3.1( +) expression vector containing a shRNA sequence targeting enhanced green
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Epigenetics and genome stability. Mamm. Genome (IF 2.287) Pub Date : 2020-04-15 Justina X Feng,Nicole C Riddle
Maintaining genome stability is essential to an organism's health and survival. Breakdown of the mechanisms protecting the genome and the resulting genome instability are an important aspect of the aging process and have been linked to diseases such as cancer. Thus, a large network of interconnected pathways is responsible for ensuring genome integrity in the face of the continuous challenges that
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Tissue-specific epigenetic inheritance after paternal heat exposure in male wild guinea pigs. Mamm. Genome (IF 2.287) Pub Date : 2020-04-13 Alexandra Weyrich,Selma Yasar,Dorina Lenz,Jörns Fickel
External temperature change has been shown to modify epigenetic patterns, such as DNA methylation, which regulates gene expression. DNA methylation is heritable, and as such provides a mechanism to convey environmental information to subsequent generations. Studies on epigenetic response to temperature increase are still scarce in wild mammals, even more so studies that compare tissue-specific epigenetic
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Epigenetic contribution to obesity. Mamm. Genome (IF 2.287) Pub Date : 2020-04-11 Meriem Ouni,Annette Schürmann
Obesity is a worldwide epidemic and contributes to global morbidity and mortality mediated via the development of nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), cardiovascular (CVD) and other diseases. It is a consequence of an elevated caloric intake, a sedentary lifestyle and a genetic as well as an epigenetic predisposition. This review summarizes changes in DNA methylation and
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Advances of single-cell genomics and epigenomics in human disease: where are we now? Mamm. Genome (IF 2.287) Pub Date : 2020-04-08 Rizqah Kamies,Celia P Martinez-Jimenez
Cellular heterogeneity is revolutionizing the way to study, monitor and dissect complex diseases. This has been possible with the technological and computational advances associated to single-cell genomics and epigenomics. Deeper understanding of cell-to-cell variation and its impact on tissue function will open new avenues for early disease detection, accurate diagnosis and personalized treatments
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Creation and characterization of an immortalized canine myoblast cell line: Myok9. Mamm. Genome (IF 2.287) Pub Date : 2020-04-03 Sara Mata López,Cynthia Balog-Alvarez,Emily H Canessa,Yetrib Hathout,Kristy J Brown,Stanislav Vitha,Amanda K Bettis,Jessica Boehler,Joe N Kornegay,Peter P Nghiem
The availability of an in vitro canine cell line would reduce the need for dogs for primary in vitro cell culture and reduce overall cost in pre-clinical studies. An immortalized canine muscle cell line, named Myok9, from primary myoblasts of a normal dog has been developed by the authors. Immortalization was performed by SV40 viral transfection of the large T antigen into the primary muscle cells
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Comparative genomic analysis of inbred rat strains reveals the existence of ancestral polymorphisms. Mamm. Genome (IF 2.287) Pub Date : 2020-03-12 Hyeonjeong Kim,Minako Yoshihara,Mikita Suyama
In an alignment of closely related genomic sequences, the existence of discordant mutation sites, which do not reflect the phylogenetic relationship of the genomes, is often observed. Although these discordant mutation sites are thought to have emerged by ancestral polymorphism or gene flow, their frequency and distribution in the genome have not yet been analyzed in detail. Using the genome sequences
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33rd international mammalian genome conference: meeting highlights. Mamm. Genome (IF 2.287) Pub Date : 2020-03-02 Lauren J Tracey,Kelsey E Noll,Xavier Montagutelli
Scientists from 12 countries met at the International Mammalian Genome Conference (IMGC) to share advances in mammalian genetics and genomics research. The event was held in Strasbourg, France and represents the city's second time hosting the IMGC. A diverse attendance of pre-doctoral and post-doctoral trainees, young investigators, established researchers, clinicians, bioinformaticians, and computational
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A novel mutation in the mouse Pcsk1 gene showing obesity and diabetes. Mamm. Genome (IF 2.287) Pub Date : 2020-01-23 Nor I A Muhsin,Liz Bentley,Ying Bai,Michelle Goldsworthy,Roger D Cox
The proprotein convertase subtilisin/Kexin type 1 (PCSK1/PC1) protein processes inactive pro-hormone precursors into biologically active hormones in a number of neuroendocrine and endocrine cell types. Patients with recessive mutations in PCSK1 exhibit a complex spectrum of traits including obesity, diarrhoea and endocrine disorders. We describe here a new mouse model with a point mutation in the Pcsk1
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PATHBIO: an international training program for precision mouse phenotyping. Mamm. Genome (IF 2.287) Pub Date : 2020-02-22 Jesus Ruberte,Paul N Schofield,Cord Brakebusch,Peter Vogel,Yann Herault,Guillem Gracia,Colin McKerlie,Martin Hrabĕ de Angelis,Michael Hagn,John P Sundberg
Design and production of genetically engineered mouse strains by individual research laboratories, research teams, large-scale consortia, and the biopharmaceutical industry have magnified the need for qualified personnel to identify, annotate, and validate (phenotype) these potentially new mouse models of human disease. The PATHBIO project has been recently established and funded by the European Union's
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Ectopic expression of the Stabilin2 gene triggered by an intracisternal A particle (IAP) element in DBA/2J strain of mice. Mamm. Genome (IF 2.287) Pub Date : 2020-01-07 Nobuyo Maeda-Smithies,Sylvia Hiller,Sharlene Dong,Hyung-Suk Kim,Brian J Bennett,Yukako Kayashima
Stabilin2 (Stab2) encodes a large transmembrane protein which is predominantly expressed in the liver sinusoidal endothelial cells (LSECs) and functions as a scavenger receptor for various macromolecules including hyaluronans (HA). In DBA/2J mice, plasma HA concentration is ten times higher than in 129S6 or C57BL/6J mice, and this phenotype is genetically linked to the Stab2 locus. Stab2 mRNA in the
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A comprehensive and comparative phenotypic analysis of the collaborative founder strains identifies new and known phenotypes. Mamm. Genome (IF 2.287) Pub Date : 2020-02-14 Heike Kollmus,Helmut Fuchs,Christoph Lengger,Hamed Haselimashhadi,Molly A Bogue,Manuela A Östereicher,Marion Horsch,Thure Adler,Juan Antonio Aguilar-Pimentel,Oana Veronica Amarie,Lore Becker,Johannes Beckers,Julia Calzada-Wack,Lillian Garrett,Wolfgang Hans,Sabine M Hölter,Tanja Klein-Rodewald,Holger Maier,Philipp Mayer-Kuckuk,Gregor Miller,Kristin Moreth,Frauke Neff,Birgit Rathkolb,Ildikó Rácz,Jan
The collaborative cross (CC) is a large panel of mouse-inbred lines derived from eight founder strains (NOD/ShiLtJ, NZO/HILtJ, A/J, C57BL/6J, 129S1/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). Here, we performed a comprehensive and comparative phenotyping screening to identify phenotypic differences and similarities between the eight founder strains. In total, more than 300 parameters including allergy
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Candidate genes and gene markers for the resistance to porcine pleuropneumonia. Mamm. Genome (IF 2.287) Pub Date : 2020-01-20 Florian Nietfeld,Doris Höltig,Hermann Willems,Peter Valentin-Weigand,Christine Wurmser,Karl-Heinz Waldmann,Ruedi Fries,Gerald Reiner
Actinobacillus (A.) pleuropneumoniae is one of the most important respiratory pathogens in global pig production. Antimicrobial treatment and vaccination provide only limited protection, but genetic disease resistance is a very promising alternative for sustainable prophylaxis. Previous studies have discovered multiple QTL that may explain up to 30% of phenotypic variance. Based on these findings,
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Genome-wide scans identify known and novel regions associated with prolificacy and reproduction traits in a sub-Saharan African indigenous sheep (Ovis aries). Mamm. Genome (IF 2.287) Pub Date : 2019-11-22 Asrat Tera Dolebo,Negar Khayatzadeh,Aberra Melesse,David Wragg,Mourad Rekik,Aynalem Haile,Barbara Rischkowsky,Max F Rothschild,Joram M Mwacharo
Maximizing the number of offspring born per female is a key functionality trait in commercial- and/or subsistence-oriented livestock enterprises. Although the number of offspring born is closely associated with female fertility and reproductive success, the genetic control of these traits remains poorly understood in sub-Saharan Africa livestock. Using selection signature analysis performed on Ovine
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The JAX Synteny Browser for mouse-human comparative genomics. Mamm. Genome (IF 2.287) Pub Date : 2019-11-27 Georgi Kolishovski,Anna Lamoureux,Paul Hale,Joel E Richardson,Jill M Recla,Omoluyi Adesanya,Al Simons,Govindarajan Kunde-Ramamoorthy,Carol J Bult
Visualizing regions of conserved synteny between two genomes is supported by numerous software applications. However, none of the current applications allow researchers to select genome features to display or highlight in blocks of synteny based on the annotated biological properties of the features (e.g., type, function, and/or phenotype association). To address this usability gap, we developed an
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Mouse model of the human serotonin transporter-linked polymorphic region. Mamm. Genome (IF 2.287) Pub Date : 2019-11-22 Lukasz Piszczek,Simone Memoli,Angelo Raggioli,José Viosca,Jeanette Rientjes,Philip Hublitz,Weronika Czaban,Anna Wyrzykowska,Cornelius Gross
Genetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified
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Crim1C140S mutant mice reveal the importance of cysteine 140 in the internal region 1 of CRIM1 for its physiological functions. Mamm. Genome (IF 2.287) Pub Date : 2019-11-27 Tatsuya Furuichi,Manami Tsukamoto,Masaki Saito,Yuriko Sato,Nobuyasu Oiji,Kazuhiro Yagami,Ryutaro Fukumura,Yoichi Gondo,Long Guo,Shiro Ikegawa,Yu Yamamori,Kentaro Tomii
Cysteine-rich transmembrane bone morphogenetic protein regulator 1 (CRIM1) is a type I transmembrane protein involved in the organogenesis of many tissues via its interactions with growth factors including BMP, TGF-β, and VEGF. In this study, we used whole-exome sequencing and linkage analysis to identify a novel Crim1 mutant allele generated by ENU mutagenesis in mice. This allele is a missense mutation
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Allele substitution and dominance effects of CD166/ALCAM gene polymorphisms for endoparasite resistance and test-day traits in a small cattle population using logistic regression analyses. Mamm. Genome (IF 2.287) Pub Date : 2019-10-24 Katharina May,Christina Weimann,Carsten Scheper,Christina Strube,Sven König
The study investigated the effects of four single-nucleotide polymorphisms (SNPs) in the activated leukocyte cell adhesion molecule (ALCAM) gene on liver fluke (Fasciola hepatica) infections (FH-INF), gastrointestinal nematode infections (GIN-INF) and disease indicator traits [e.g. somatic cell score (SCS), fat-to-protein ratio (FPR)] in German dual-purpose cattle (DSN). A genome-wide association study
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Hepatic gene expression variations in response to high-fat diet-induced impaired glucose tolerance using RNAseq analysis in collaborative cross mouse population. Mamm. Genome (IF 2.287) Pub Date : 2019-10-24 H J Abu-Toamih Atamni,G Kontogianni,I Binenbaum,R Mott,H Himmelbauer,H Lehrach,A Chatziioannou,Fuad A Iraqi
Hepatic gene expression is known to differ between healthy and type 2 diabetes conditions. Identifying these variations will provide better knowledge to the development of gene-targeted therapies. The aim of this study is to assess diet-induced hepatic gene expression of susceptible versus resistant CC lines to T2D development. Next-generation RNA-sequencing was performed for 84 livers of diabetic
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The gut microbiota modulates differential adenoma suppression by B6/J and B6/N genetic backgrounds in ApcMin mice. Mamm. Genome (IF 2.287) Pub Date : 2019-09-23 Jacob E Moskowitz,Federica Andreatta,James Amos-Landgraf
Tumor multiplicity in the ApcMin (Min) mouse model of CRC is a classic quantitative trait that is subject to complex genetic and environmental factors, and therefore serves as an ideal platform to study modifiers of disease. While disparate inbred genetic backgrounds have well-characterized modifying effects on tumor multiplicity, it is unclear whether more closely related backgrounds such as C57BL/6J
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Mice expressing the variant rs1143679 allele of ITGAM (CD11b) show impaired DC-mediated T cell proliferation. Mamm. Genome (IF 2.287) Pub Date : 2019-10-31 Justin T Avery,Rachel V Jimenez,Joseph L Blake,Tyler T Wright,Beatriz Leόn-Ruiz,Trenton R Schoeb,Alexander J Szalai,Daniel C Bullard
Genome-wide association studies (GWAS) and functional genomic analyses have implicated several ITGAM (CD11b) single-nucleotide polymorphisms (SNPs) in the development of SLE and other disorders. ITGAM encodes the αM chain of the β2 integrin Mac-1, a receptor that plays important roles in myeloid cell functions. The ITGAM SNP rs1143679, which results in an arginine to histidine change at amino acid
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miR-129-5p improves cardiac function in rats with chronic heart failure through targeting HMGB1. Mamm. Genome (IF 2.287) Pub Date : 2019-10-23 Na Xiao,Jun Zhang,Chao Chen,Yanfang Wan,Ning Wang,Jing Yang
Increasing evidence shows that miRNAs play pivotal roles in cardiovascular diseases, including heart failure (HF). The aim of this study was to investigate the role of miR-129-5p in chronic heart failure and the underlying mechanisms. The levels of miR-129-5p and HMGB1 in chronic heart failure patients (CHF) and normal controls were examined by RT-qPCR and ELISA. Cardiac function, hemodynamics parameters
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Transposable element-mediated structural variation analysis in dog breeds using whole-genome sequencing. Mamm. Genome (IF 2.287) Pub Date : 2019-08-15 Songmi Kim,Seyoung Mun,Taemook Kim,Kang-Hoon Lee,Keunsoo Kang,Je-Yoel Cho,Kyudong Han
Naturally occurring diseases in dogs provide an important animal model for studying human disease including cancer, heart disease, and autoimmune disorders. Transposable elements (TEs) make up ~ 31% of the dog (Canis lupus familiaris) genome and are one of main drivers to cause genomic variations and alter gene expression patterns of the host genes, which could result in genetic diseases. To detect
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The dark genome and pleiotropy: challenges for precision medicine. Mamm. Genome (IF 2.287) Pub Date : 2019-08-23 Steve D M Brown,Heena V Lad
Surprisingly we remain ignorant of the function of the majority of genes in the human and mouse genomes. The dark genome is a major obstacle to the interpretation of the function of human genetic variation and its impact on disease. At the same time, pleiotropy, how individual variants influence multiple phenotypes, is key to understanding gene function and the role of genes and genetic networks in
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Exploring the dark genome: implications for precision medicine. Mamm. Genome (IF 2.287) Pub Date : 2019-07-04 Tudor I Oprea
The increase in the number of both patients and healthcare practitioners who grew up using the Internet and computers (so-called "digital natives") is likely to impact the practice of precision medicine, and requires novel platforms for data integration and mining, as well as contextualized information retrieval. The "Illuminating the Druggable Genome Knowledge Management Center" (IDG KMC) quantifies
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Precision and Functional Genomics. Mamm. Genome (IF 2.287) Pub Date : 2020-02-01 Steve D M Brown,Joseph H Nadeau
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Closing the 'phenotype gap' in precision medicine: improving what we measure to understand complex disease mechanisms. Mamm. Genome (IF 2.287) Pub Date : 2019-08-19 Calum A MacRae
The central concept underlying precision medicine is a mechanistic understanding of each disease and its response to therapy sufficient to direct a specific intervention. To execute on this vision requires parsing incompletely defined disease syndromes into discrete mechanistic subsets and developing interventions to precisely address each of these etiologically distinct entities. This will require
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Liver size and lipid content differences between BALB/c and BALB/cJ mice on a high-fat diet are due, in part, to Zhx2. Mamm. Genome (IF 2.287) Pub Date : 2019-07-18 Erica L Clinkenbeard,Courtney Turpin,Jieyun Jiang,Martha L Peterson,Brett T Spear
BALB/cJ mice exhibit considerable phenotypic differences with other BALB/c substrains. Some of these traits involve the liver, including persistent postnatal expression of genes that are normally expressed only in the fetal liver and reduced expression of major urinary proteins. These traits are due to a mutation that dramatically reduces expression of the gene encoding the transcription factor Zinc
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Amplification of lncRNA PVT1 promotes ovarian cancer proliferation by binding to miR-140. Mamm. Genome (IF 2.287) Pub Date : 2019-06-20 Yuqin Ding,Qianjin Fang,Yan Li,Yanni Wang
Gene deletion or gene amplification acts as a driving factor of onset, progress, and metastasis in various cancers, including ovarian cancers. By mining the whole genome data of ovarian cancer patients, we identify the long noncoding RNA PVT1 as the most amplified gene. Knockdown of PVT1 was then achieved using a shRNA in two ovarian cancer cell lines, and cell viability was determined by trypan blue
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Uses for humanised mouse models in precision medicine for neurodegenerative disease. Mamm. Genome (IF 2.287) Pub Date : 2019-06-15 Remya R Nair,Silvia Corrochano,Samanta Gasco,Charlotte Tibbit,David Thompson,Cheryl Maduro,Zeinab Ali,Pietro Fratta,Abraham Acevedo Arozena,Thomas J Cunningham,Elizabeth M C Fisher
Neurodegenerative disease encompasses a wide range of disorders afflicting the central and peripheral nervous systems and is a major unmet biomedical need of our time. There are very limited treatments, and no cures, for most of these diseases, including Alzheimer's Disease, Parkinson's Disease, Huntington Disease, and Motor Neuron Diseases. Mouse and other animal models provide hope by analysing them
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Precision medicine and Mammalian Genome. Mamm. Genome (IF 2.287) Pub Date : 2019-06-01 Steve D M Brown,Joseph H Nadeau
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New models for human disease from the International Mouse Phenotyping Consortium. Mamm. Genome (IF 2.287) Pub Date : 2019-05-24 Pilar Cacheiro,Melissa A Haendel,Damian Smedley,
The International Mouse Phenotyping Consortium (IMPC) continues to expand the catalogue of mammalian gene function by conducting genome and phenome-wide phenotyping on knockout mouse lines. The extensive and standardized phenotype screens allow the identification of new potential models for human disease through cross-species comparison by computing the similarity between the phenotypes observed in
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Inbreeding depression causes reduced fecundity in Golden Retrievers. Mamm. Genome (IF 2.287) Pub Date : 2019-05-21 Erin T Chu,Missy J Simpson,Kelly Diehl,Rodney L Page,Aaron J Sams,Adam R Boyko
Inbreeding depression has been demonstrated to impact vital rates, productivity, and performance in human populations, wild and endangered species, and in recent years, the domestic species. In all cases, standardized, high-quality phenotype data on all individuals are invaluable for longitudinal analyses such as those required to evaluate vital rates of a study cohort. Further, many investigators
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Chronic and age-dependent effects of the spongiform neurodegeneration-associated MGRN1 E3 ubiquitin ligase on mitochondrial homeostasis. Mamm. Genome (IF 2.287) Pub Date : 2019-05-14 Teresa M Gunn,Derek Silvius,Andrew Lester,Britney Gibbs
Spongiform encephalopathy is an intriguing yet poorly understood neuropathology characterized by vacuoles, demyelination, and gliosis. It is observed in patients with prion disease, primary mitochondrial disease, HIV-1 infection of the brain, and some inherited disorders, but the underlying mechanism of disease remains unclear. The brains of mice lacking the MGRN1 E3 ubiquitin ligase develop vacuoles
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The guanine nucleotide exchange factor, Spata13, influences social behaviour and nocturnal activity. Mamm. Genome (IF 2.287) Pub Date : 2019-04-26 Nora Bourbia,Paige Chandler,Gemma Codner,Gareth Banks,Patrick M Nolan
Spermatogenesis-associated protein 13 (Spata13) is a guanine nucleotide exchange factor (GEF) enriched in discrete brain regions in the adult, with pronounced expression in the extended central amygdala (CeA). Loss of Spata13, also known as the adenomatous polyposis coli exchange factor Asef2, has no identifiable phenotype although it has been shown to reduce the number and size of intestinal tumours
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A high-density genetic map and molecular sex-typing assay for gerbils. Mamm. Genome (IF 2.287) Pub Date : 2019-04-12 Thomas D Brekke,Sushmita Supriya,Megan G Denver,Angharad Thom,Katherine A Steele,John F Mulley
We constructed a high-density genetic map for Mongolian gerbils (Meriones unguiculatus). We genotyped 137 F2 individuals with a genotype-by-sequencing (GBS) approach at over 10,000 loci and built the genetic map using a two-step approach. First, we chose the highest-quality set of 485 markers to construct a robust map of 1239 cM with 22 linkage groups as expected from the published karyotype. Second
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Model validity for preclinical studies in precision medicine: precisely how precise do we need to be? Mamm. Genome (IF 2.287) Pub Date : 2019-04-05 Abigail L D Tadenev,Robert W Burgess
The promise of personalized medicine is that each patient's treatment can be optimally tailored to their disease. In turn, their disease, as well as their response to the treatment, is determined by their genetic makeup and the "environment," which relates to their general health, medical history, personal habits, and surroundings. Developing such optimized treatment strategies is an admirable goal
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Meeting report: 32nd international mammalian genome conference. Mamm. Genome (IF 2.287) Pub Date : 2019-04-01 Jacob Moskowitz,Lauren Tracey,Samuel Widmayer,Beth Dumont
Over 150 scientists from more than 50 research institutions and eight countries attended the 32nd annual meeting of the International Mammalian Genome Society (IMGS) held in Rio Mar, Puerto Rico. Attendees included predoctoral and postdoctoral trainees, junior investigators, clinicians, industry professionals, and established leaders in mammalian genetics and genomics. From November 11-14, major scientific
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Analysis and preliminary validation of the molecular mechanism of fat deposition in fatty and lean pigs by high-throughput sequencing. Mamm. Genome (IF 2.287) Pub Date : 2019-03-08 Jing Xiang Cui,Qi Fan Zeng,Wei Chen,Hong Zhang,Yong Qing Zeng
Fat deposition in muscle includes intramuscular fat (IMF) and intermuscular fat. IMF content is an index of pork quality; however, because IMF content is difficult to measure in vivo in young animals, conventional breeding for IMF content is difficult to carry out. The mechanism and progression of animal fat deposition is not well understood, and there are currently no effective control methods. In
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Humanized mouse models of immunological diseases and precision medicine. Mamm. Genome (IF 2.287) Pub Date : 2019-03-07 Leonard D Shultz,James Keck,Lisa Burzenski,Sonal Jangalwe,Shantashri Vaidya,Dale L Greiner,Michael A Brehm
With the increase in knowledge resulting from the sequencing of the human genome, the genetic basis for the underlying differences in individuals, their diseases, and how they respond to therapies is starting to be understood. This has formed the foundation for the era of precision medicine in many human diseases that is beginning to be implemented in the clinic, particularly in cancer. However, preclinical
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Treating Rett syndrome: from mouse models to human therapies. Mamm. Genome (IF 2.287) Pub Date : 2019-02-28 Neeti Vashi,Monica J Justice
Rare diseases are very difficult to study mechanistically and to develop therapies for because of the scarcity of patients. Here, the rare neuro-metabolic disorder Rett syndrome (RTT) is discussed as a prototype for precision medicine, demonstrating how mouse models have led to an understanding of the development of symptoms. RTT is caused by mutations in the X-linked gene methyl-CpG-binding protein
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Evidence for a de novo, dominant germ-line mutation causative of osteogenesis imperfecta in two Red Angus calves. Mamm. Genome (IF 2.287) Pub Date : 2019-02-23 Jessica L Petersen,Shauna M Tietze,Rachel M Burrack,David J Steffen
A genetic disorder, osteogenesis imperfecta (OI) is broadly characterized by connective tissue abnormalities and bone fragility most commonly attributed to alterations in Type I collagen. Two Red Angus calves by the same sire presented with severe bone and dental fragility, blue sclera, and evidence of in utero fractures consistent with OI congenita. Comparative analyses with human cases suggested
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Genetic variation in thyroid folliculogenesis influences susceptibility to hypothyroidism-induced hearing impairment. Mamm. Genome (IF 2.287) Pub Date : 2019-02-18 Amanda H Mortensen,Qing Fang,Michelle T Fleming,Thomas J Jones,Alexandre Z Daly,Kenneth R Johnson,Sally A Camper
Maternal and fetal sources of thyroid hormone are important for the development of many organ systems. Thyroid hormone deficiency causes variable intellectual disability and hearing impairment in mouse and man, but the basis for this variation is not clear. To explore this variation, we studied two thyroid hormone-deficient mouse mutants with mutations in pituitary-specific transcription factors, POU1F1
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Fearful old world? A commentary on the Second International Summit on human genome editing. Mamm. Genome (IF 2.287) Pub Date : 2019-01-03 Andy Greenfield
Genome editing is revolutionising our ability to modify genomes with exquisite precision for medical and agricultural applications, and in basic research. The first International Summit on Human Genome Editing, organised jointly by the US National Academies of Sciences and Medicine, the Chinese Academy of Sciences and the UK Royal Society, was held in Washington DC at the end of 2015. Its aim was to
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A deletion in the Ctns gene causes renal tubular dysfunction and cystine accumulation in LEA/Tohm rats. Mamm. Genome (IF 2.287) Pub Date : 2018-12-29 Yukiko Shimizu,Rieko Yanobu-Takanashi,Kenta Nakano,Kenji Hamase,Toshiaki Shimizu,Tadashi Okamura
The Long-Evans Agouti (LEA/Tohm) rat has recently been established as a new rat model of type 2 diabetes. The onset of diabetes mellitus was observed only in male LEA/Tohm rats; however, urinary glucose appeared before the onset of diabetes. To clarify the genetic basis of urinary glucose, we performed genetic linkage analysis using (BN × LEA) F2 intercross progeny. A recessively acting locus responsible