Article
Biotechnology & Applied Microbiology
Wilson Nandolo, Gabor Meszaros, Maria Wurzinger, Liveness J. Banda, Timothy N. Gondwe, Henry A. Mulindwa, Helen N. Nakimbugwe, Emily L. Clark, M. Jennifer Woodward-Greene, Mei Liu, George E. Liu, Curtis P. Van Tassell, Benjamin D. Rosen, Johann Solkner
Summary: This study focused on African goats and developed a detailed copy number variation map, identifying a large number of CNVs with substantial differentiation between populations and population-specific selective pressures. A total of 6231 global CNV regions were identified across all animals, containing genes enriched in important biological functions and cellular components.
Article
Biochemistry & Molecular Biology
Ana Rita Marques, Joao Xavier Santos, Hugo Martiniano, Joana Vilela, Celia Rasga, Luisa Romao, Astrid Moura Vicente
Summary: This study investigates the role of the Nonsense-Mediated mRNA Decay (NMD) pathway in Autism Spectrum Disorder (ASD) and identifies many genetic variants associated with NMD genes in ASD patients, suggesting a potential involvement of NMD in ASD pathophysiology.
Article
Multidisciplinary Sciences
Wouter Steyaert, Lonneke Haer-Wigman, Rolph Pfundt, Debby Hellebrekers, Marloes Steehouwer, Juliet Hampstead, Elke de Boer, Alexander Stegmann, Helger Yntema, Erik-Jan Kamsteeg, Han Brunner, Alexander Hoischen, Christian Gilissen
Summary: This paper presents a method called "Chameleolyser" that accurately identifies variants in duplicated genomic regions. Application of this method to a large cohort of exome samples led to the identification of a significant number of rare variants, including those that resulted in direct molecular diagnoses for previously undiagnosed patients.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Amy B. Wilfert, Tychele N. Turner, Shwetha C. Murali, PingHsun Hsieh, Arvis Sulovari, Tianyun Wang, Bradley P. Coe, Hui Guo, Kendra Hoekzema, Trygve E. Bakken, Lara H. Winterkorn, Uday S. Evani, Marta Byrska-Bishop, Rachel K. Earl, Raphael A. Bernier, Michael C. Zody, Evan E. Eichler
Summary: Whole-genome sequencing data from 3,474 families revealed an excess of private, likely gene-disrupting variants in individuals with autism, which are under purifying selection. The study identified candidate genes not previously associated with autism and highlighted the importance of ultra-rare variants in autism risk. Private LGD variants were found to be significantly younger and act on a distinct set of genes, supporting a multi-hit model for autism.
Review
Genetics & Heredity
Tianyun Wang, Peiyao A. Zhao, Evan E. Eichler
Summary: This study provides evidence supporting an oligogenic model in which two or more ultrarare mutations with modest effects are preferentially transmitted to children with autism. These private gene-disruptive mutations are enriched in families with multiple affected individuals, emerged two or three generations ago, and map to genes not previously associated with autism. Although no single gene has reached statistical significance, this class of variation should be considered along with genetic and nongenetic factors to better explain the etiology of this complex trait.
TRENDS IN GENETICS
(2022)
Article
Biochemical Research Methods
Fei Qin, Xizhi Luo, Guoshuai Cai, Feifei Xiao
Summary: This study explores the correlation structure of whole-exome sequencing (WES) data and introduces a novel correlation-based CNV detection method, CORRseq, which outperforms existing methods in detecting medium and large CNVs. Modeling genomic correlation structure is advantageous for detecting relatively long CNVs.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Oncology
Cody Ashby, Eileen M. Boyle, Michael A. Bauer, Aneta Mikulasova, Christopher P. Wardell, Louis Williams, Ariel Siegel, Patrick Blaney, Marc Braunstein, David Kaminetsky, Jonathan Keats, Francesco Maura, Ola Landgren, Brian A. Walker, Faith E. Davies, Gareth J. Morgan
Summary: Deciphering genomic architecture helps identify disease drivers and understand myeloma initiation and progression mechanisms. This study demonstrates that structural variants occur nonrandomly in the genome, and their frequencies vary in different genetic contexts. The study also reveals the heterogeneity of transcriptional dysregulation caused by both canonical and novel structural variants, as well as the impact of complex rearrangements on clinical outcomes. Chromothripsis, in particular, has a significant negative effect on clinical outcome.
BLOOD CANCER JOURNAL
(2022)
Article
Genetics & Heredity
Shizhen Chen, Liming Lu, Jianfeng Xian, Changhong Shi, Jinbin Chen, Boqi Rao, Fuman Qiu, Jiachun Lu, Lei Yang
Summary: This study developed a prognostic nomogram for NSCLC based on gCNVs and validated two gCNVs associated with NSCLC overall survival in a Chinese population. The high polygenic risk score (PRS) calculated from CNVR395.1 and CNVR2239.1 showed significantly higher death rates in both the training and validation cohorts. The nomogram, incorporating PRS and other factors, demonstrated good predictive performance and calibration in predicting NSCLC survival, with an observed interaction between PRS and asbestos exposure.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Jhih-Rong Lin, Yingjie Zhao, M. Reza Jabalameli, Nha Nguyen, Joydeep Mitra, Ann Swillen, Jacob A. S. Vorstman, Eva W. C. Chow, Marianne van den Bree, Beverly S. Emanuel, Joris R. Vermeesch, Michael J. Owen, Nigel M. Williams, Anne S. Bassett, Donna M. McDonald-McGinn, Raquel E. Gur, Carrie E. Bearden, Bernice E. Morrow, Herbert M. Lachman, Zhengdong D. Zhang
Summary: 22q11.2 deletion is a strong genetic risk factor for schizophrenia. Whole-genome sequencing of schizophrenia cases and controls with this deletion revealed the effects of rare coding variants in modifier genes, contributing to the pathogenesis of schizophrenia. The modifier genes affected synaptic function and developmental disorders and were coexpressed with 22q11.2 genes in specific brain regions.
MOLECULAR PSYCHIATRY
(2023)
Review
Biochemical Research Methods
Mian Umair Ahsan, Qian Liu, Jonathan Elliot Perdomo, Li Fang, Kai Wang
Summary: As long-read sequencing technologies become more popular, various methods have been developed for detecting and analyzing structural variants (SVs) from long reads. These methods are needed to adapt to the unique challenges and opportunities presented by long-read sequencing. This review summarizes more than 50 long-read-based methods for SV detection, genotyping, and visualization, and discusses how new telomere-to-telomere genome assemblies and pangenome efforts can enhance accuracy and drive the development of SV callers in the future.
Article
Biochemistry & Molecular Biology
David R. Porubsky, Mitchell T. Vollger, William N. Harvey, Allison Rozanski, Peter Ebert, Glenn Hickey, Patrick D. Hasenfeld, Ashley Sanders, Catherine O. Stober, Jan Korbel, Benedict E. Paten, Tobias Marschall, Evan Eichler
Summary: There has been significant progress in phased genome assembly by combining long-read data with parental information or linked-read data. However, the typical phased genome assembly still has over 140 gaps. A detailed analysis of 182 haploid assemblies reveals that the majority of assembly gaps cluster near large and identical repeats, resulting in disrupted protein-coding genes. Misorientations and alignment discontinuities are also identified, highlighting the need for algorithmic development and pangenome representation.
Article
Genetics & Heredity
Cedrik Tekendo-Ngongang, Angela Grochowsky, Benjamin D. Solomon, Sho T. Yano
Summary: Various variants of the FMR1 gene have been shown to cause disease phenotypes, including splicing variants, missense variants, full deletions, nonsense variants, and frameshift variants. In addition, FMR1 deletions may not only occur in patients with mosaic full mutations, but also in patients with normal-sized CGG repeats, suggesting genomic instability in the CGG repeat region. Clinical tests for potential FMR1-related indications should include methods capable of detecting small coding, noncoding, and copy number variants.
Article
Multidisciplinary Sciences
Shukmei Wong, E. J. Ehrhart, Samuel Stewart, Victoria Zismann, Jacob Cawley, Rebecca Halperin, Natalia Briones, Keith Richter, Karthigayini Sivaprakasam, Nieves Perdigones, Tania Contente-Cuomo, Salvatore Facista, Jeffrey M. Trent, Muhammed Murtaza, Chand Khanna, William P. D. Hendricks
Summary: Cancer genomic heterogeneity is a significant challenge in understanding cancer processes and clinical management. The study of canine splenic hemangiosarcoma revealed both intertumoral and intratumoral genomic heterogeneity. This research provides valuable insights into the origin and clinical impact of cancer heterogeneity.
Article
Biochemistry & Molecular Biology
Catherine A. Brownstein, Richard S. Smith, Lance H. Rodan, Mark P. Gorman, Margaret A. Hojlo, Emily A. Garvey, Jianqiao Li, Kristin Cabral, Joshua J. Bowen, Abhijit S. Rao, Casie A. Genetti, Devon Carroll, Emma A. Deaso, Pankaj B. Agrawal, Jill A. Rosenfeld, Weimin Bi, Jennifer Howe, Dimitri J. Stavropoulos, Adam W. Hansen, Hesham M. Hamoda, Ferne Pinard, Annmarie Caracansi, Christopher A. Walsh, Eugene J. D'Angelo, Alan H. Beggs, Mehdi Zarrei, Richard A. Gibbs, Stephen W. Scherer, David C. Glahn, Joseph Gonzalez-Heydrich
Summary: Mendelian and early-onset severe psychiatric phenotypes often involve genetic variants with large effects, offering opportunities for genetic discoveries and early therapeutic interventions. In this study, a stop-gain mutation in the RCL1 gene was identified in an 18-year-old boy with cognitive decline, leading to the discovery of RCL1 copy number variations in multiple patients with varying neurodevelopmental or psychiatric phenotypes. These findings suggest that dosage variation of RCL1 contributes to a range of neurological and clinical phenotypes.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Anna Minaidou, Stella Tamana, Coralea Stephanou, Maria Xenophontos, Cornelis L. Harteveld, Celeste Bento, Marina Kleanthous, Petros Kountouris
Summary: This article presents an online tool called IthaCNVs, which aids in the diagnosis of haemoglobinopathies associated with copy number variants (CNVs). The tool allows filtering of entries based on breakpoint information, chromosomal and locus positions, MLPA probes, and affected genes, assisting laboratory staff and clinicians in confirming the diagnosis of CNVs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pediatrics
Amy Pan, Sierra Scodellaro, Tayyaba Khan, Inna Ushcatz, Wendy Wu, Meredith Curtis, Eyal Cohen, Ronald D. Cohn, Robin Z. Hayeems, M. Stephen Meyn, Julia Orkin, Jaskiran Otal, Miriam S. Reuter, Susan Walker, Stephen W. Scherer, Christian R. Marshall, Iris Cohn, Gregory Costain
Summary: Genome-wide sequencing can provide clinically relevant pharmacogenetic information for children with medical complexity, enabling precision prescribing practices throughout their lifelong care.
PEDIATRIC RESEARCH
(2023)
Article
Genetics & Heredity
Muhammad Faheem, Eric Deneault, Roumiana Alexandrova, Deivid C. C. Rodrigues, Giovanna Pellecchia, Carole Shum, Mehdi Zarrei, Alina Piekna, Wei Wei, Jennifer L. L. Howe, Bhooma Thiruvahindrapuram, Sylvia Lamoureux, P. Joel Ross, Clarrisa A. A. Bradley, James Ellis, Stephen W. W. Scherer
Summary: The PTCHD1 gene deletion is associated with autism spectrum disorder (ASD). Mutations that extend beyond PTCHD1-AS/DDX53 to PTCHD1 result in ASD and intellectual disability (ID). However, a study found that DDX53 mutation does not alter the function of NGN2 neurons, suggesting that synaptic deficits are unlikely to cause ASD in this cell type.
BMC MEDICAL GENOMICS
(2023)
Article
Genetics & Heredity
Qiliang Ding, Cherith Somerville, Roozbeh Manshaei, Brett Trost, Miriam S. Reuter, Kelsey Kalbfleisch, Kaitlin Stanley, John B. A. Okello, S. Mohsen Hosseini, Eriskay Liston, Meredith Curtis, Mehdi Zarrei, Edward J. Higginbotham, Ada J. S. Chan, Worrawat Engchuan, Bhooma Thiruvahindrapuram, Stephen W. Scherer, Raymond H. Kim, Rebekah K. Jobling
Summary: This study introduces SCIP, a software package that enables efficient and accurate clinical interpretation of CNVs, facilitating improved genetic diagnoses.
Article
Biochemistry & Molecular Biology
Zain Awamleh, Sanaa Choufani, Cheryl Cytrynbaum, Fowzan S. Alkuraya, Stephen Scherer, Sofia Fernandes, Catarina Rosas, Pedro Louro, Patricia Dias, Mariana Tomasio Neves, Sergio B. Sousa, Rosanna Weksberg
Summary: Pathogenic variants in ANKRD11 or microdeletions at 16q24.3 cause KBG syndrome and are associated with unique DNAm signatures. These DNAm profiles can be used for diagnostic purposes and can help classify individuals with variants of uncertain significance in ANKRD11.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Brianna K. Unda, Leon Chalil, Sehyoun Yoon, Savannah Kilpatrick, Courtney Irwin, Sansi Xing, Nadeem Murtaza, Anran Cheng, Chad Brown, Alexandria Afonso, Elizabeth McCready, Gabriel M. Ronen, Jennifer Howe, Aurelie Caye-Eude, Alain Verloes, Brad W. Doble, Laurence Faivre, Antonio Vitobello, Stephen W. Scherer, Yu Lu, Peter Penzes, Karun K. Singh
Summary: Copy number variations (CNVs) are associated with psychiatric and neurodevelopmental disorders (NDDs), and the underlying disease mechanisms for most CNVs are unknown. In this study, a 15q13.3 microdeletion mouse model and patient iPSC-derived neurons were used to investigate the developmental defects caused by the CNV. By targeting the 15q13.3 CNV genetic driver OTUD7A, the study revealed a critical OTUD7A-Ankyrin pathway in neuronal development and dysfunction in the 15q13.3 microdeletion syndrome.
MOLECULAR PSYCHIATRY
(2023)
Article
Oncology
Anita Villani, Scott Davidson, Nisha Kanwar, Winnie W. W. Lo, Yisu Li, Sarah Cohen-Gogo, Fabio Fuligni, Lisa-Monique Edward, Nicholas Light, Mehdi Layeghifard, Ricardo Harripaul, Larissa Waldman, Bailey Gallinger, Federico Comitani, Ledia Brunga, Reid Hayes, Nathaniel D. D. Anderson, Arun K. K. Ramani, Kyoko E. E. Yuki, Sasha Blay, Brittney Johnstone, Cara Inglese, Rawan Hammad, Catherine Goudie, Andrew Shuen, Jonathan D. D. Wasserman, Rosemarie E. E. Venier, Marianne Eliou, Miranda Lorenti, Carol Ann Ryan, Michael Braga, Meagan Gloven-Brown, Jianan A. Han, Maria Montero, Famida Spatare, James A. A. Whitlock, Stephen W. W. Scherer, Kathy Chun, Martin J. J. Somerville, Cynthia Hawkins, Mohamed Abdelhaleem, Vijay Ramaswamy, Gino R. R. Somers, Lianna Kyriakopoulou, Johann Hitzler, Mary Shago, Daniel A. A. Morgenstern, Uri Tabori, Stephen Meyn, Meredith S. S. Irwin, David Malkin, Adam Shlien
Summary: We conducted integrative somatic-germline analyses on 300 cancer patients, sequencing 864 cancer-associated genes, complete genomes, and transcriptomes. Clinically actionable variants were found in 56% of patients, leading to modified management in some cases. Therapeutically targetable variants, derived from both somatic and germline sources, were present in 54% of patients.
Article
Genetics & Heredity
Dmitrijs Rots, Taryn E. Jakub, Crystal Keung, Vissers E. L. M. Lisenka, Siddharth Banka, Rolph Pfundt, Bert B. A. de Vries, Richard H. van Jaarsveld, Saskia M. J. Hopman, Ellen van Binsbergen, Irene Valenzuela, Maja Hempel, Tatjana Bierhals, Fanny Kortuem, Francois Lecoquierre, Alice Goldenberg, Jens Michael Hertz, Charlotte Brasch Andersen, Maria Kibaek, Eloise J. Prijoles, Roger E. Stevenson, David B. Everman, Wesley G. Patterson, Linyan Meng, Charul Gijavanekar, Karl De Dios, Shenela Lakhani, Tess Levy, Matias Wagner, Dagmar Wieczorek, Paul J. Benke, Maria Soledad Lopez Garcia, Renee Perrier, Sergio B. Sousa, Pedro M. Almeida, Maria Jose Simoes, Bertrand Isidor, Wallid Deb, Andrew A. Schmanski, Omar Abdul-Rahman, Christophe Philippe, Ange-Line Bruel, Laurence Faivre, Antonio Vitobello, Christel Thauvin, Jeroen J. Smits, Livia Garavelli, Stefano G. Caraffi, Francesca Peluso, Laura Davis-Keppen, Dylan Platt, Erin Royer, Lisette Leeuwen, Margje Sinnema, Alexander P. A. Stegmann, Constance T. R. M. Stumpel, George E. Tiller, Danielle G. M. Bosch, Stephanus T. Potgieter, Shelagh Joss, Miranda Splitt, Simon Holden, Matina Prapa, Nicola Foulds, Sofia Douzgou, Kaija Puura, Regina Waltes, Andreas G. Chiocchetti, Christine M. Freitag, F. Kyle Satterstrom, Silvia De Rubeis, Joseph Buxbaum, Bruce D. Gelb, Aleksic Branko, Itaru Kushima, Jennifer Howe, Stephen W. Scherer, Alessia Arado, Chiara Baldo, Olivier Patat, Demeer Benedicte, Diego Lopergolo, Filippo M. Santorelli, Tobias B. Haack, Andreas Dufke, Miriam Bertrand, Ruth J. Falb, Angelika Riess, Peter Krieg, Stephanie Spranger, Maria Francesca Bedeschi, Maria Iascone, Sarah Josephi-Taylor, Tony Roscioli, Michael F. Buckley, Jan Liebelt, Aditi I. Dagli, Emmelien Aten, Anna C. E. Hurst, Alesha Hicks, Mohnish Suri, Ermal Aliu, Sunil Naik, Richard Sidlow, Juliette Coursimault, Gael Nicolas, Hanna Kuepper, Florence Petit, Veyan Ibrahim, Deniz Top, Francesca Di Cara, Raymond J. Louie, Elliot Stolerman, Han G. Brunner, Lisenka E. L. M. Vissers, Jamie M. Kramer, Tjitske Kleefstra
Summary: This study examines the clinical and molecular spectrum of individuals with KDM6B variants and challenges the accuracy of the current description of the disorder. Cognitive deficits are consistently observed, but the overall phenotype varies greatly. The study also demonstrates the disruptive effect of certain KDM6B variants on protein structure and introduces a functional testing paradigm for assessing these variants. The findings highlight the importance of international collaboration and rigorous functional analysis in diagnosing rare disorders.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Alanna Strong, Soumya Rao, Sandra von Hardenberg, Dong Li, Liza L. Cox, Paul C. Lee, Li Q. Zhang, Waheed Awotoye, Tamir Diamond, Jessica Gold, Catherine Gooch, Lord Jephthah Joojo Gowans, Hakon Hakonarson, Anne Hing, Kathleen Loomes, Nicole Martin, Mary L. Marazita, Tarja Mononen, David Piccoli, Rolph Pfundt, Salmo Raskin, Stephen W. Scherer, Nara Sobriera, Courtney Vaccaro, Xiang Wang, Deborah Watson, Rosanna Weksberg, Elizabeth Bhoj, Jeffrey C. Murray, Andrew C. Lidral, Azeez Butali, Michael F. Buckley, Tony Roscioli, David A. Koolen, Laurie H. Seaver, Cynthia A. Prows, Rolf W. Stottmann, Timothy C. Cox
Summary: AMOTL1 encodes angiomotin-like protein 1, a protein that regulates cell polarity, adhesion, and migration. Variants in AMOTL1 are associated with orofacial clefting, congenital heart disease, tall stature, auricular anomalies, and gastrointestinal manifestations. The study suggests that missense variants in AMOTL1, particularly in the region affecting amino acids 157-161, define a new orofacial clefting syndrome and highlight the importance of this region in its function.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Pharmacology & Pharmacy
Luciana Bertholim-Nasciben, Marilia O. Scliar, Guilherme Debortoli, Bhooma Thiruvahindrapuram, Stephen W. Scherer, Yeda A. O. Duarte, Mayana Zatz, Guilherme Suarez-Kurtz, Esteban J. Parra, Michel S. Naslavsky
Summary: This study evaluated the frequency of pharmacogenomics markers in the Brazilian population using whole-genome sequencing. The findings showed that some variants may lead to high-risk gene-drug interactions. The study concluded that next-generation sequencing for pharmacogenomics testing is feasible in the Brazilian population.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Genetics & Heredity
S. Yoo, E. Garg, L. T. Elliott, R. J. Hung, A. R. Halevy, J. D. Brooks, S. B. Bull, F. Gagnon, C. M. T. Greenwood, J. F. Lawless, A. D. Paterson, L. Sun, M. H. Zawati, J. Lerner-Ellis, R. J. S. Abraham, I Birol, G. Bourque, J-m Garant, C. Gosselin, J. Li, J. Whitney, B. Thiruvahindrapuram, J-a Herbrick, M. Lorenti, M. S. Reuter, O. O. Adeoye, S. Liu, U. Allen, F. P. Bernier, C. M. Biggs, A. M. Cheung, J. Cowan, M. Herridge, D. M. Maslove, B. P. Modi, V Mooser, S. K. Morris, M. Ostrowski, R. S. Parekh, G. Pfeffer, O. Suchowersky, J. Taher, J. Upton, R. L. Warren, R. S. M. Yeung, N. Aziz, S. E. Turvey, B. M. Knoppers, M. Lathrop, S. J. M. Jones, S. W. Scherer, L. J. Strug
Summary: HostSeq was launched in April 2020 to integrate whole genome sequencing data and clinical information of 10,000 Canadians infected with SARS-CoV-2. It aims to support research communities in understanding disease risk factors and developing interventions. HostSeq is a collaboration among 13 epidemiological studies across five provinces in Canada, providing aggregated data through two portals and individual-level data for global health research.
Article
Behavioral Sciences
Danielle A. Baribeau, Jasleen Arneja, Xuesong Wang, Jennifer Howe, John R. McLaughlin, Karen Tu, Jun Guan, Alana Iaboni, Elizabeth Kelley, Muhammad Ayub, Robert Nicolson, Stelios Georgiades, Stephen W. Scherer, Susan E. Bronskill, Evdokia Anagnostou, Jennifer D. Brooks
Summary: This study aimed to determine whether carrying an autism-associated rare genetic variant is associated with differences in health system utilization by autistic children and youth. The study found that participants with a rare variant impacting an autism-associated gene were less likely to have received psychiatric care, but there were no differences in health care costs and the proportion with complex chronic medical conditions.
Article
Genetics & Heredity
Mona Abdi, Elbay Aliyev, Brett Trost, Muhammad Kohailan, Waleed Aamer, Najeeb Syed, Rulan Shaath, Geethanjali Devadoss Gandhi, Worrawat Engchuan, Jennifer Howe, Bhooma Thiruvahindrapuram, Melissa Geng, Joe Whitney, Amira Syed, Jyothi Lakshmi, Sura Hussein, Najwa Albashir, Amal Hussein, Ilaria Poggiolini, Saba F. Elhag, Sasirekha Palaniswamy, Marios Kambouris, Maria de Fatima Janjua, Mohamed O. El Tahir, Ahsan Nazeer, Durre Shahwar, Muhammad Waqar Azeem, Younes Mokrab, Nazim Abdel Aati, Ammira Akil, Stephen W. Scherer, Madeeha Kamal, Khalid A. Fakhro
Summary: This study identified potentially pathogenic variants in ASD families in Qatar, with a significant proportion being single-gene variants. It also highlighted the impact of recessive variation on the ASD architecture in consanguineous settings, providing a unique genomic resource for future ASD research in the global community.
Article
Biology
Miriam S. Reuter, Dustin J. Sokolowski, J. Javier Diaz-Mejia, Johannes Keunen, Barbra de Vrijer, Cadia Chan, Liangxi Wang, Greg Ryan, David A. Chiasson, Troy Ketela, Stephen W. Scherer, Michael D. Wilson, Edgar Jaeggi, Rajiv R. Chaturvedi
Summary: Low blood flow through the fetal left heart can lead to hypoplastic left heart syndrome (HLHS). In this study, mid-gestation fetal lambs were used to create left ventricular inflow obstruction (LVIO) to investigate the effects of decreased left heart flow. The results showed that significant LVIO led to clinical features similar to HLHS, including decreased aortic valve flow, retrograde perfusion, severe left heart hypoplasia, and changes in cellular composition and gene expression consistent with fibrosis and abnormal mesenchymal programs.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Eduardo A. Maury, Maxwell A. Sherman, Giulio Genovese, Thomas G. Gilgenast, Tushar Kamath, S. J. Burris, Prashanth Rajarajan, Erin Flaherty, Schahram Akbarian, Andrew Chess, Steven A. McCarroll, Po-Ru Loh, Jennifer E. Phillips-Cremins, Kristen J. Brennand, Evan Z. Macosko, James T. R. Walters, Michael O'Donovan, Patrick Sullivan, Jonathan Sebat, Eunjung A. Lee, Christopher A. Walsh
Summary: This study suggests that somatic copy-number variants (sCNVs) may play a potential role in the risk of schizophrenia (SCZ). Early-developmental sCNVs were more common in SCZ cases, including recurrent somatic deletions in the NRXN1 gene. Additionally, recurrent intragenic deletions of the ABCB11 gene were observed in treatment-resistant SCZ cases.
Article
Genetics & Heredity
Salma Shickh, Chloe Mighton, Marc Clausen, Rita Kodida, Ella Adi-Wauran, Daena Hirjikaka, Suvetha Krishnapillai, Emma Reble, Jordan Sam, Nancy N. Baxter, Andreas Laupacis, Yvonne Bombard
Summary: This study aims to explore the patient-reported utility of cancer results from genomic sequencing (GS). Results showed that patients' perceptions of the utility of GS results were dependent on whether they triggered clinical action. Patients who received results without clinical action became hypervigilant and experienced negative effects. Therefore, there is a need to develop practice interventions to support cancer patients undergoing GS.
GENETICS IN MEDICINE
(2023)