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.
Article
Biochemistry & Molecular Biology
Marie Saitou, Naoki Masuda, Omer Gokcumen
Summary: This study developed a new method to identify potentially adaptive structural variants and discovered hundreds of such variants using various analytical approaches. The study also revealed the associations of these variants with genotype frequency, coding sequences, and GWAS traits, and introduced new evolutionary models to explain the complexity of structural variant evolution.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Endocrinology & Metabolism
Maria Stamou, Harrison Brand, Mei Wang, Isaac Wong, Margaret F. Lippincott, Lacey Plummer, William F. Crowley, Michael Talkowski, Stephanie Seminara, Ravikumar Balasubramanian
Summary: This study found that copy number variants (CNVs) in known genes contribute to approximately 2% of isolated hypogonadotropic hypogonadism (IHH) pathogenesis. Multigenic contiguous CNVs resulted in syndromic phenotypes, while single gene CNVs also caused syndromic phenotypes, validating the pleiotropy of some IHH genes.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Clinical Neurology
Kari A. Mattison, Gilles Tossing, Fred Mulroe, Callum Simmons, Kameryn M. Butler, Alison Schreiber, Adnan Alsadah, Derek E. Neilson, Karin Naess, Anna Wedell, Anna Wredenberg, Arthur Sorlin, Emma McCann, George J. Burghel, Beatriz Menendez, George E. Hoganson, Lorenzo D. Botto, Francis M. Filloux, Angel Aledo-Serrano, Antonio Gil-Nagel, Katrina Tatton-Brown, Nienke E. Verbeek, Bert van der Zwaag, Kyrieckos A. Aleck, Andrew C. Fazenbaker, Jorune Balciuniene, Holly A. Dubbs, Eric D. Marsh, Kathryn Garber, Jakob Ek, Morten Duno, Christina E. Hoei-Hansen, Matthew A. Deardorff, Gordana Raca, Catherine Quindipan, Michele Van Hirtum-Das, Jeroen Breckpot, Trine Bjorg Hammer, Rikke S. Moller, Andrea Whitney, Andrew G. L. Douglas, Mira Kharbanda, Nicola Brunetti-Pierri, Manuela Morleo, Vincenzo Nigro, Halie J. May, James X. Tao, Emanuela Argilli, Elliot H. Sherr, William B. Dobyns, Richard A. Baines, Jim Warwicker, J. Alex Parker, Siddharth Banka, Philippe M. Campeau, Andrew Escayg
Summary: This study identifies ATP6V0C as an important disease gene associated with neurodevelopmental abnormalities. The mutations in ATP6V0C affect the activity of vacuolar H+-ATPase and lead to decreased cell growth, motor dysfunction, and reduced lifespan.
Article
Genetics & Heredity
Xueya Zhou, Pamela Feliciano, Chang Shu, Tianyun Wang, Irina Astrovskaya, Jacob B. Hall, Joseph U. Obiajulu, Jessica R. Wright, Shwetha C. Murali, Simon Xuming Xu, Leo Brueggeman, Taylor R. Thomas, Olena Marchenko, Christopher Fleisch, Sarah D. Barns, LeeAnne Green Snyder, Bing Han, Timothy S. Chang, Tychele N. Turner, William T. Harvey, Andrew Nishida, Brian J. O'Roak, Daniel H. Geschwind, Jacob J. Michaelson, Natalia Volfovsky, Evan E. Eichler, Yufeng Shen, Wendy K. Chung
Summary: In a comprehensive analysis of autism cases, we identified 60 genes, including five new risk genes, that are significantly associated with autism risk. The NAV3 gene is primarily associated with autism risk through rare inherited variants and has a moderate effect. Autistic individuals with moderate-risk genes show less cognitive impairment compared to those with highly penetrant genes.
Article
Multidisciplinary Sciences
Triin Kikas, Anna Maria Punab, Laura Kasak, Olev Poolamets, Vladimir Vihljajev, Kristjan Pomm, Mario Reiman, Stanislav Tjagur, Paul Korrovits, Margus Punab, Maris Laan
Summary: This study analyzed the genome-wide CNV profile in men with SPGF and found that the proportion of CNVs >1 Mb was twice as high in SPGF patients compared to controls. Additionally, seven patients carried microdeletions or microduplications that were linked to severe congenital conditions.
SCIENTIFIC REPORTS
(2023)
Article
Psychiatry
Xavier Caseras, George Kirov, Kimberley M. Kendall, Elliott Rees, Sophie E. Legge, Matthew Bracher-Smith, Valentina Escott-Price, Kevin Murphy
Summary: The study revealed that carriers of rare copy number variants associated with schizophrenia showed reduced surface area, increased cortical thickness, and heightened thickness covariance across gyri in the brain. These changes were predominantly found in frontal and parietal areas and were driven by a limited number of rare risk alleles. The heterogeneity in the effects of rare risk alleles suggests potential different neurobiological pathways into the phenotype of schizophrenia.
BRITISH JOURNAL OF PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Maria del Pilar Chantada-Vazquez, Susana B. Bravo, Sofia Barbosa-Gouveia, Jose V. Alvarez, Maria L. Couce
Summary: Inherited metabolic disorders (IMDs) are rare medical conditions caused by genetic defects that affect the body's metabolism. Early diagnosis and understanding of the disease are crucial, and proteomics and tandem mass spectrometry (MS/MS) have emerged as valuable tools for studying IMDs. Proteomics can aid in the identification of biomarkers, early diagnosis, and better understanding of the underlying pathology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Yoann Vial, Elodie Lainey, Thierry Leblanc, Veronique Baudouin, Marie Emilie Dourthe, Pierre Gressens, Alain Verloes, Helene Cave, Severine Drunat
Summary: We identified a likely pathogenic variant in NUF2 in a patient with severe microcephaly, congenital bone marrow failure, growth retardation, and renal hypoplasia, which impairs the cell's ability to properly complete mitosis. This finding suggests a unifying causal role of the variant in Fanconi Anaemia, highlighting the unique pathological link between neurogenesis and haematopoiesis.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Genetics & Heredity
Thomas Eggermann, Florian Kraft, Eva Lausberg, Katrin Ergezinger, Erdmute Kunstmann
Summary: This study identified a family with a 132 bp deletion within the KCNQ1OT1 gene, which is associated with growth retardation when paternally transmitted but results in a normal phenotype when maternally inherited. Comparisons with cases from the literature helped to determine the functional relevance of this microdeletion within the paternal imprinting center 2 affecting the KCNQ1OT1 gene.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Genetics & Heredity
Emma S. Singer, Samantha B. Ross, Jon R. Skinner, Robert G. Weintraub, Jodie Ingles, Christopher Semsarian, Richard D. Bagnall
Summary: This study utilized recent gene curation efforts and technical standards to characterize clinically relevant CNVs in patients with inherited heart disease and sudden cardiac death. In 690 unrelated probands, eight CNVs were identified, with three being classified as pathogenic and some CNVs being linked to ancestral events. Identifying precise breakpoint junctions proved useful for interpreting the clinical relevance of CNVs.
GENETICS IN MEDICINE
(2021)
Review
Hematology
Usua Oyarbide, Genevieve M. Crane, Seth J. Corey
Summary: Neutrophils, the shortest-lived blood cells, require extensive proliferation and differentiation to maintain sufficient numbers and respond quickly to infections. Defects in cellular metabolism resulting from monogenic disorders can lead to congenital neutropenias. Understanding metabolic pathways could identify new strategies for treating neutropenias.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
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
Francis Ramond, Caroline Dalgliesh, Mona Grimmel, Oded Wechsberg, Annalisa Vetro, Renzo Guerrini, David FitzPatrick, Rebecca L. Poole, Marine Lebrun, Allan Bayat, Ute Grasshoff, Miriam Bertrand, Dennis Witt, Peter D. Turnpenny, Victor Faundes, Lorena Santa Maria, Carolina Mendoza Fuentes, Paulina Mabe, Shaun A. Hussain, Sureni V. Mullegama, Erin Torti, Barbara Oehl-Jaschkowitz, Lina Basel Salmon, Naama Orenstein, Noa Ruhrman Shahar, Ofir Hagari, Lily Bazak, Sabine Hoffjan, Carlos E. Prada, Tobias Haack, David J. Elliott
Summary: This study aims to associate germline variants in the TRA2B gene with a novel neurodevelopmental disorder. Through RNA sequencing and western blot analyses, it was found that these variants resulted in a new neurodevelopmental syndrome.
GENETICS IN MEDICINE
(2023)