Article
Biochemistry & Molecular Biology
Keiji Ogura, Yoshiko Ayabe, Chihiro Harada, Ignacia Braga Tanaka, Satoshi Tanaka, Jun-ichiro Komura
Summary: This study reported the transgenerational effects of chronic low dose-rate irradiation in mice, revealing an increase in de novo copy number variations in the offspring of irradiated male mice. However, no significant difference was found in the size of the de novo deletions between the irradiated and non-irradiated groups. Further analysis suggested a potential association between de novo copy-number variations and shorter life spans.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Igor N. Lebedev, Tatyana Karamysheva, Eugeny A. Elisaphenko, Alexey Makunin, Daria Zhigalina, Maria E. Lopatkina, Gleb Drozdov, Aleksander D. Cheremnykh, Natalia B. Torkhova, Gulnara N. Seitova, Stanislav A. Vasilyev, Anna A. Kashevarova, Ludmila P. Nazarenko, Nikolay B. Rubtsov
Summary: The case study presented a prenatal diagnosis of a foetus with mosaic sSMC(10) and identified a ring structure derived from chromosome 10 with specific regions involved. Despite the presence of a 9 Mb euchromatin region, the sSMC did not result in clinical manifestations and a healthy girl was born. The study suggests that the ring structure of sSMCs could influence their manifestations and should be considered in genetic counselling during prenatal diagnosis.
Article
Biochemistry & Molecular Biology
Donatella Conconi, Serena Redaelli, Andrea Alberto Lissoni, Chiara Cilibrasi, Patrizia Perego, Eugenio Gautiero, Elena Sala, Mariachiara Paderno, Leda Dalpra, Fabio Landoni, Marialuisa Lavitrano, Gaia Roversi, Angela Bentivegna
Summary: The study analyzed the genomic and epigenomic profiles of uterine smooth muscle tumors, finding similarities between STUMPs and LMSs. Some genes with potential prognostic value, previously not associated with STUMP, were identified. Methylation data showed promise, especially in samples with divergent profiles, and Gene Ontology analysis highlighted cancer genes that may serve as prognostic markers in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Nicoletta Villa, Serena Redaelli, Stefania Farina, Donatella Conconi, Elena Maria Sala, Francesca Crosti, Silvana Mariani, Carla Maria Colombo, Leda Dalpra, Marialuisa Lavitrano, Angela Bentivegna, Gaia Roversi, Mario Ventura
Summary: Complex chromosomal rearrangements are rare events that can occur and be compatible with survival. They involve an imbalance and/or position effect of one or more genes, resulting in a variety of clinical presentations. Investigating and diagnosing these cases can be challenging. Understanding the pairing and segregation patterns of these chromosomes during meiosis is crucial for assessing the risk and type of imbalance in offspring.
Article
Medicine, General & Internal
Chung-Lin Lee, Chih-Kuang Chuang, Ru-Yi Tu, Huei-Ching Chiu, Yun-Ting Lo, Ya-Hui Chang, Yen-Jiun Chen, Chao-Ling Chou, Peih-Shan Wu, Chih-Ping Chen, Hsiang-Yu Lin, Shuan-Pei Lin
Summary: This study aimed to determine the diagnostic yield of array-CGH in ASD patients from a Taiwanese cohort. The results showed a satisfactory diagnostic yield of array-CGH in Taiwanese ASD patients, supporting its clinical usefulness as a first-line testing method for ASD.
MEDICINA-LITHUANIA
(2022)
Article
Education, Special
C. Palka Bayard de Volo, M. Alfonsi, E. Morizio, P. Guaciali-Franchi, A. Mohn, F. Chiarelli
Summary: The use of array-comparative genomic hybridization in analyzing a cohort of 343 Italian patients with ID, MCA, and ASD revealed a high detection rate of chromosomal abnormalities. The abnormalities were classified into three major groups based on their pathogenic significance, with a higher number of deletions in the pathogenic group. The study highlights the complexity of CNV classification and the importance of patient selection in interpreting molecular cytogenetic results.
JOURNAL OF INTELLECTUAL DISABILITY RESEARCH
(2021)
Article
Obstetrics & Gynecology
Elisa Spataro, Adalgisa Cordisco, Carlo Luchi, Gilda Rosaria Filardi, Giulia Masini, Lucia Pasquini
Summary: The objective of this study was to determine the residual risk of morbidity-related outcome in fetuses with nuchal translucency (NT) of 3.5 mm or more after normal genetic testing and mid-trimester anomaly scan. The results showed that the residual risk of morbidity-related outcome was 24.64% for NT 3.5-4.5 mm, 25% for NT 4.5-6 mm, and 76.47% for NT more than 6 mm. After a normal RASopathy testing and mid-trimester anomaly scan, the residual risks decreased to 7.14%, 8.69%, and 33.3% in the three groups, respectively.
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
(2023)
Article
Biochemistry & Molecular Biology
Shristi Bhattarai, Bruna M. Sugita, Stefanne M. Bortoletto, Aline S. Fonseca, Luciane R. Cavalli, Ritu Aneja
Summary: TNBCs can be further classified into AR-positive and AR-negative subtypes, with AR-negative tumors showing higher levels of CNAs and a higher frequency of cases affected by CNAs. QNBCs and TNBCs exhibit similar CNAs in CIN25 and CA signatures, but QNBCs have higher expression levels of CIN25 and CA20 genes. miRNA profiling identified differentially expressed miRNAs associated with genomic instability, with eight miRNAs showing concordance of expression and copy number levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Danielle Rodrigues Cortez, Fabio Mitsuo Lima, Joao Luis Reis-Cunha, Daniella Castanheira Bartholomeu, Rolando Andre Rios Villacis, Silvia Regina Rogatto, Andre Guilherme Costa-Martins, Fernanda Sycko Marchiano, Rafaela Andrade do Carmo, Jose Franco da Silveira, Marjorie Mendes Marini
Summary: In this study, the genetic differences between two lineages of Chagas disease-causing parasite T. cruzi were analyzed using intraspecific array-based comparative genomic hybridization (aCGH). The results showed that clone D11 had more chromosomal gains and losses compared to the parental G strain. These genomic changes suggest a dynamic genome in clone D11 that responds to environmental stress by altering gene copy numbers and generating segmental aneuploidy.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Cell Biology
Elisabet Lloveras, Anna Canellas, Alberto Plaja, Laura Barranco, Daniel Fernandez, Begona Mendez, Meritxell Pique, Cristina de la Iglesia, Nuria Palau, Marta Costa, Marta Herrero, Diana Yeste, Marc Auge, Laia Puig, Cristina Perez
Summary: The use of new technologies has revealed new mechanisms for structural variation in the human genome, such as the phenomenon of chromothripsis, posing challenges for genetic counseling.
CYTOGENETIC AND GENOME RESEARCH
(2021)
Article
Genetics & Heredity
Chin-Chieh Hsu, Chien-Hong Lee, Shuenn-Dyh Chang, Tsang-Ming Ko, Shir-Hwa Ueng, Yu-Hsiu Chen, Mei-Chia Wang, Yao-Lung Chang
Summary: This article presents a unique case of placental mesenchymal dysplasia with fetal chromosomal anomaly, and provides insights into the possible pathogenesis and embryogenesis through detailed molecular testing and mosaic analysis.
Article
Cell Biology
Diana Corallo, Carlo Zanon, Marcella Pantile, Gian Paolo Tonini, Angelica Zin, Samuela Francescato, Bartolomeo Rossi, Eva Trevisson, Claudia Pinato, Ezequiel Monferrer, Rosa Noguera, Salvador F. Alino, Maria Jose Herrero, Alessandra Biffi, Elisabetta Viscardi, Sanja Aveic
Summary: The genetic landscape of an aggressive NB has been depicted through comprehensive analysis, combining CNAs, SNVs, and SNPs analyses along with characterization of 3D tumoroids. The integrated approach proved powerful in evaluating clonal evolution and dynamic genomic alterations during disease progression and therapy administration, enhancing disease follow-up and tumor recurrence prediction.
Article
Biochemistry & Molecular Biology
Ni-Chen Chang, Quirze Rovira, Jonathan Wells, Cedric Feschotte, Juan M. Vaquerizas
Summary: This study describes the demography and genomic distribution of zebrafish transposable elements (TEs) and their expression during embryogenesis. The results reveal a highly dynamic genomic ecosystem comprising nearly 2000 distinct TE families, with longer retroelements being retained in intergenic regions and shorter elements more frequently found near or within genes. The study provides a valuable resource for using zebrafish as a model to study the impact of TEs on vertebrate development.
Article
Biology
Martina Giambra, Eleonora Messuti, Andrea Di Cristofori, Clarissa Cavandoli, Raffaele Bruno, Raffaella Buonanno, Matilde Marzorati, Melissa Zambuto, Virginia Rodriguez-Menendez, Serena Redaelli, Carlo Giussani, Angela Bentivegna
Summary: The genomic landscape of glioblastoma and its components, such as the stem cell compartment and peritumoral brain zone, is still incomplete. Research has shown the key role of stem cells in tumor maintenance and drug resistance, as well as the importance of the marginal area where tumor recurrences often occur. By analyzing the genomic profiles of different components, new specific biomarkers have been identified for potential therapies.
Article
Clinical Neurology
Akiko Hiraiwa, Kou Matsui, Yumi Nakayama, Takao Komatsubara, Shinichi Magara, Yu Kobayashi, Moemi Hojo, Mitsuhiro Kato, Toshiyuki Yamamoto, Jun Tohyama
Summary: This report describes a patient with Pallister-Killian syndrome (PKS) showing unique polymicrogyria with calcifications. The patient exhibited delayed development and dysmorphic facial features, with genetic analysis revealing mosaic duplication of chromosome 12p. The findings suggest that somatic mosaicism of tetrasomy in PKS could lead to asymmetrical polymicrogyria, possibly involving increased dosages of CCND2.
BRAIN & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Reuben M. Buckley, Alex C. Harris, Guo-Dong Wang, D. Thad Whitaker, Ya-Ping Zhang, Elaine A. Ostrander
Summary: The study compared the accuracy and performance of low-pass whole genome sequencing and imputation in dogs, demonstrating that by optimizing a variant quality filtering strategy, the imputation error rate can be reduced and approximately 80% of imputed sites retained. For case-control GWAS, where small effect sizes were most impacted, guidelines for best practices in low-pass WGS-imputed genotypes in dogs were provided.
Article
Genetics & Heredity
Ashley Moller-Hansen, Stephanie Huynh, Cornelius F. Boerkoel, Hui-Lin Chin
Summary: This study reports a rare case of cerebral cavernous malformations with lymphatic defects in addition to common symptoms, expanding the spectrum of KRIT1-related diseases to include lymphatic malformations and lymphatic endothelial dysfunction.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Pierre K. Boerkoel, Katherine Dixon, Carrie Fitzsimons, Yaoqing Shen, Stephanie Huynh, Kamilla Schlade-Bartusiak, Luka Culibrk, Simon Chan, Cornelius F. Boerkoel, Steven J. M. Jones, Hui-Lin Chin
Summary: This study reports a newborn with syndromic degenerative anophthalmia and a complex de novo rearrangement of chromosome 13q. Long-read genome sequencing improved the resolution and clinical interpretation of the rearrangement, providing new insights into the molecular etiology of MAC.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Hui-Lin Chin, Stephanie Huynh, Jahanshah Ashkani, Michael Castaldo, Katherine Dixon, Kathryn Selby, Yaoqing Shen, Marie Wright, Cornelius F. Boerkoel, Glenda Hendson, Steven J. M. Jones
Summary: Monoallelic pathogenic variants in BICD2 cause autosomal dominant Spinal Muscular Atrophy Lower Extremity Predominant 2A and 2B. Dysfunction of BICD2 leads to motor neuron loss. A novel de novo BICD2 variant was identified in a patient with diaphragmatic paralysis without typical muscle weakness and contractures, expanding the phenotypic spectrum of BICD2-related disease.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Biochemistry & Molecular Biology
Jocelyn Plassais, Bridgett M. vonHoldt, Heidi G. Parker, Alberto Carmagnini, Nicolas Dubos, Ilenia Papa, Kevin Bevant, Thomas Derrien, Lauren M. Hennelly, D. Thad Whitaker, Alex C. Harris, Andrew N. Hogan, Heather J. Huson, Victor F. Zaibert, Anna Linderholm, James Haile, Thierry Fest, Bilal Habib, Benjamin N. Sacks, Norbert Benecke, Alan K. Outram, Mikhail Sablin, Mietje Germonpre, Greger Larson, Laurent Frantz, Elaine A. Ostrander
Summary: Domestic dogs display a 40-fold size difference between breeds, with body size being regulated by multiple genes. Insulin-like growth factor 1 (IGF1) is the main regulator, controlling approximately 15% of the body size variation. By analyzing genome sequences from different species, researchers identified a variant in an antisense long non-coding RNA (IGF1-AS) that interacts with the IGF1 gene, resulting in the dominance of derived mutation in modern wolves and large domestic breeds.
Article
Genetics & Heredity
Praveen F. Cherukuri, Melissa M. Soe, David E. Condon, Shubhi Bartaria, Kaitlynn Meis, Shaopeng Gu, Frederick G. Frost, Lindsay M. Fricke, Krzysztof P. Lubieniecki, Joanna M. Lubieniecka, Robert E. Pyatt, Catherine Hajek, Cornelius F. Boerkoel, Lynn Carmichael
Summary: The study validates the analytical accuracy of GSA genotyping through quality assessment and comparison with benchmark and rWGS data, meeting clinical screening standards. However, caution is advised for GSA assays targeting rare variants, transversions, and variants within low-complexity regions.
BMC MEDICAL GENOMICS
(2022)
Meeting Abstract
Hematology
Jason E. Farrar, Jenny L. Smith, Megan Othus, Benjamin J. Huang, Yi-Cheng Wang, Rhonda E. Ries, Tiffany A. Hylkema, Era L. Pogosova-Agadjanyan, Sneha Challa, Amanda R. Leonti, Timothy Shaw, Timothy Junius Triche, Alan S. Gamis, Richard Aplenc, Anders E. Kolb, Xiaotu Ma, Derek Stirewalt, Todd A. Alonzo, Soheil Meshinchi
Meeting Abstract
Hematology
Akiko Shimamura, Alexey Maschan, Carolyn Bennett, Jason E. Farrar, Sujith Samarasinghe, Brigitte Strahm, Winfred C. Wang, Adrianna Vlachos, Charlotte M. Niemeyer, Timothy S. Olson, Denise D'Alessio, Elise Burmeister Getz, Tomasz Lawniczek, Yunnan Xu, David A. Williams
Meeting Abstract
Hematology
Adam J. Lamble, Rhonda E. Ries, Todd A. Alonzo, Yi-Cheng Wang, Jason E. Farrar, Benjamin J. Huang, Matthew A. Kutny, Jessica A. Pollard, Richard Aplenc, Alan S. Gamis, Edward A. Kolb, Todd M. Cooper, Soheil Meshinchi
Article
Medicine, General & Internal
Julia Handra, Adrienne Elbert, Nour Gazzaz, Ashley Moller-Hansen, Stephanie Hyunh, Hyun Kyung Lee, Pierre Boerkoel, Emily Alderman, Erin Anderson, Lorne Clarke, Sara Hamilton, Ronnalea Hamman, Shevaun Hughes, Simon Ip, Sylvie Langlois, Mary Lee, Laura Li, Frannie Mackenzie, Millan S. S. Patel, Leah M. M. Prentice, Karan Sangha, Laura Sato, Kimberly Seath, Margaret Seppelt, Anne Swenerton, Lynn Warnock, Jessica L. Zambonin, Cornelius F. Boerkoel, Hui-Lin Chin, Linlea Armstrong
Summary: Genomic medicine is an emerging medical discipline that applies the principles of evolution, developmental biology, functional genomics, and structural genomics within clinical care. Enabling the integration of genomic medicine into clinical practice is crucial for achieving precision medicine. This paper provides a biological framework for diagnostic utility of genomic testing, and outlines the process of genomic medicine integration into clinical practice.
FRONTIERS IN MEDICINE
(2023)
Article
Genetics & Heredity
Ashley Moller-Hansen, Duha Hejla, Hyun Kyung Lee, Jenea Barbara Lyles, Yunhan Yang, Kun Chen, Wenhui Laura Li, Gary Thomas, Cornelius F. Boerkoel
Summary: PACS1-neurodevelopmental disorder (PACS1-NDD) is associated with recurrent variation of Arg203 and considered diagnostic of PACS1-NDD, an autosomal dominant syndromic intellectual disability disorder. The proposed disease mechanism for this variant is altered PACS1 affinity for its client proteins. In this study, a novel PACS1 variant (NM_018026.3:c.[755C>T];[=], p.(Ser252Phe)) is found to interfere with binding of the adaptor protein GGA3, leading to phenotypic features overlapping PACS1-NDD.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Oncology
Jason E. Farrar, Jenny L. Smith, Megan Othus, Benjamin J. Huang, Yi-Cheng Wang, Rhonda Ries, Tiffany Hylkema, Era L. Pogosova-Agadjanyan, Sneha Challa, Amanda Leonti, Timothy I. Shaw, Timothy J. Triche Jr, Alan S. Gamis, Richard Aplenc, E. Anders Kolb, Xiaotu Ma, Derek L. Stirewalt, Todd A. Alonzo, Soheil Meshinchi
Summary: Optimized risk classification strategies are crucial for personalized therapy in patients with biologically distinctive diseases. This study comprehensively evaluated the landscape of long noncoding RNA (lncRNA) transcripts in pediatric acute myeloid leukemia (pAML) and identified a 37 lncRNA signature (lncScore) associated with outcomes. The inclusion of the lncScore enhances the predictive power of traditional stratification methods in pAML, with potential to replace complex stratification schemes.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Genetics & Heredity
Marie Morimoto, Vikas Bhambhani, Nour Gazzaz, Mariska Davids, Paalini Sathiyaseelan, Ellen F. Macnamara, Jennifer Lange, Anna Lehman, Patricia M. Zerfas, Jennifer L. Murphy, Maria T. Acosta, Camille Wang, Emily Alderman, Sara Reichert, Audrey Thurm, David R. Adams, Wendy J. Introne, Sharon M. Gorski, Cornelius F. Boerkoel, William A. Gahl, Cynthia J. Tifft, May Christine V. Malicdan
Summary: This study reports three individuals from two unrelated families with a neurodevelopmental disorder characterized by speech and motor impairment, and similar facial characteristics. Rare, conserved, bi-allelic variants were identified in ATG4D gene, encoding one of four ATG4 cysteine proteases important for autophagosome biogenesis. Functional analysis revealed that these variants impair the activity of ATG4D and contribute to the pathogenesis of this syndromic neurodevelopmental disorder.
NPJ GENOMIC MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jiayi Sun, Wing-Yuk Chow, Gufeng Xu, M. John Hicks, Manjula Nakka, Jianhe Shen, Patrick Kwok Shing M. Ng, Aaron Taylor, Alexander E. Yu, Jason A. Farrar, Donald Barkauskas, Richard M. Gorlick, Jaime M. Guidry Auvil, Daniela Gerhard, Paul Meltzer, Rudy Guerra, Tsz-Kwong C. Man, Ching Lau, TARGET Osteosarcoma Consortium
Summary: Osteosarcoma is a primary malignant bone tumor that commonly metastasizes to the lungs. Altered FAS expression due to DNA methylation has been explored as a mechanism in cancer cells. Analysis revealed high variability in methylation of CpG sites that correlated with FAS mRNA expression. Treatment with demethylating agent 5-azacytidine restored FAS protein expression and reduced metastasis in osteosarcoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Taylorlyn Stephan, Shawn M. Burgess, Hans Cheng, Charles G. Danko, Clare A. Gill, Erich D. Jarvis, Klaus-Peter Koepfli, James E. Koltes, Eric Lyons, Pamela Ronald, Oliver A. Ryder, Lynn M. Schriml, Pamela Soltis, Sue VandeWoude, Huaijun Zhou, Elaine A. Ostrander, Elinor K. Karlsson
Summary: Genomics research has primarily focused on humans and a limited number of species, resulting in a lack of understanding about the genomes of the majority of species. However, a broad view that encompasses the vast diversity of life is necessary to comprehend how genomes function and how genetic variation shapes phenotypes. Integrating comparative genomics with other fields is crucial for scientific discovery and the protection of ourselves and our world.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
