Use the journals feature with a free QxMD account.
Use Read by QxMD to access full text via your institution or open access sources.
Read also provides personalized recommendations to keep you up to date in your field.
Existing User
Sign InNew to Read
Sign Up#21
JOURNAL ARTICLE
Nicholas D Johnson, David J Cutler, Karen N Conneely
Allele-specific methylation (ASM) is an epigenetic modification whereby one parental allele becomes methylated and the other unmethylated at a specific locus. ASM is most often driven by the presence of nearby heterozygous variants that influence methylation, but also occurs somatically in the context of genomic imprinting. In this study, we investigate ASM using publicly available single-cell reduced representation bisulfite sequencing (scRRBS) data on 608 B cells sampled from six healthy B cell samples and 1,230 cells from 11 chronic lymphocytic leukemia (CLL) samples...
March 5, 2024: American Journal of Human Genetics
#22
JOURNAL ARTICLE
María Del Rocío Pérez Baca, Eva Z Jacobs, Lies Vantomme, Pontus Leblanc, Elke Bogaert, Annelies Dheedene, Laurenz De Cock, Sadegheh Haghshenas, Aidin Foroutan, Michael A Levy, Jennifer Kerkhof, Haley McConkey, Chun-An Chen, Nurit Assia Batzir, Xia Wang, María Palomares, Marieke Carels, Bart Dermaut, Bekim Sadikovic, Björn Menten, Bo Yuan, Sarah Vergult, Bert Callewaert
Neurodevelopmental disorders (NDDs) result from impaired development and functioning of the brain. Here, we identify loss-of-function (LoF) variation in ZFHX3 as a cause for syndromic intellectual disability (ID). ZFHX3 is a zinc-finger homeodomain transcription factor involved in various biological processes, including cell differentiation and tumorigenesis. We describe 42 individuals with protein-truncating variants (PTVs) or (partial) deletions of ZFHX3, exhibiting variable intellectual disability and autism spectrum disorder, recurrent facial features, relative short stature, brachydactyly, and, rarely, cleft palate...
February 26, 2024: American Journal of Human Genetics
#23
JOURNAL ARTICLE
Melanie Brugger, Antonella Lauri, Yan Zhen, Laura L Gramegna, Benedikt Zott, Nikolina Sekulić, Giulia Fasano, Robert Kopajtich, Viviana Cordeddu, Francesca Clementina Radio, Cecilia Mancini, Simone Pizzi, Graziamaria Paradisi, Ginevra Zanni, Gessica Vasco, Rosalba Carrozzo, Flavia Palombo, Caterina Tonon, Raffaele Lodi, Chiara La Morgia, Maria Arelin, Cristiane Blechschmidt, Tom Finck, Vigdis Sørensen, Kornelia Kreiser, Gertrud Strobl-Wildemann, Hagit Daum, Rachel Michaelson-Cohen, Lucia Ziccardi, Giuseppe Zampino, Holger Prokisch, Rami Abou Jamra, Claudio Fiorini, Thomas Arzberger, Juliane Winkelmann, Leonardo Caporali, Valerio Carelli, Harald Stenmark, Marco Tartaglia, Matias Wagner
The endosomal sorting complex required for transport (ESCRT) machinery is essential for membrane remodeling and autophagy and it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8 (GenBank: NM_007241.4), encoding the ESCRT-II subunit SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death...
February 21, 2024: American Journal of Human Genetics
#24
JOURNAL ARTICLE
Chunling Hu, Huaizhi Huang, Jie Na, Carolyn Lumby, Mohamed Abozaid, Megan A Holdren, Tara J Rao, Rachid Karam, Tina Pesaran, Jamie D Weyandt, Christen M Csuy, Christina A Seelaus, Colin C Young, Kelly Fulk, Zahra Heidari, Paulo Cilas Morais Lyra, Ronan E Couch, Benjamin Persons, Eric C Polley, Rohan D Gnanaolivu, Nicholas J Boddicker, Alvaro N A Monteiro, Siddhartha Yadav, Susan M Domchek, Marcy E Richardson, Fergus J Couch
Variants of uncertain significance (VUSs) in BRCA2 are a common result of hereditary cancer genetic testing. While more than 4,000 unique VUSs, comprised of missense or intronic variants, have been identified in BRCA2, the few missense variants now classified clinically as pathogenic or likely pathogenic are predominantly located in the region encoding the C-terminal DNA binding domain (DBD). We report on functional evaluation of the influence of 462 BRCA2 missense variants affecting the DBD on DNA repair activity of BRCA2 using a homology-directed DNA double-strand break repair assay...
February 21, 2024: American Journal of Human Genetics
#25
JOURNAL ARTICLE
Marcello Scala, Valeria Tomati, Matteo Ferla, Mariateresa Lena, Julie S Cohen, Ali Fatemi, Elly Brokamp, Anna Bican, John A Phillips, Mary E Koziura, Michael Nicouleau, Marlene Rio, Karine Siquier, Nathalie Boddaert, Ilaria Musante, Serena Tamburro, Simona Baldassari, Michele Iacomino, Paolo Scudieri, Jill A Rosenfeld, Gary Bellus, Sara Reed, Hind Al Saif, Rossana Sanchez Russo, Matthew B Walsh, Vincent Cantagrel, Amy Crunk, Stefano Gustincich, Sarah M Ruggiero, Mark P Fitzgerald, Ingo Helbig, Pasquale Striano, Mariasavina Severino, Vincenzo Salpietro, Nicoletta Pedemonte, Federico Zara
The Rab family of guanosine triphosphatases (GTPases) includes key regulators of intracellular transport and membrane trafficking targeting specific steps in exocytic, endocytic, and recycling pathways. DENND5B (Rab6-interacting Protein 1B-like protein, R6IP1B) is the longest isoform of DENND5, an evolutionarily conserved DENN domain-containing guanine nucleotide exchange factor (GEF) that is highly expressed in the brain. Through exome sequencing and international matchmaking platforms, we identified five de novo variants in DENND5B in a cohort of five unrelated individuals with neurodevelopmental phenotypes featuring cognitive impairment, dysmorphism, abnormal behavior, variable epilepsy, white matter abnormalities, and cortical gyration defects...
February 16, 2024: American Journal of Human Genetics
#26
JOURNAL ARTICLE
Brian Z Huang, Alexandra M Binder, Brandon Quon, Yesha M Patel, Annette Lum-Jones, Maarit Tiirikainen, Sharon E Murphy, Lenora Loo, Alika K Maunakea, Christopher A Haiman, Lynne R Wilkens, Woon-Puay Koh, Qiuyin Cai, Melinda C Aldrich, Kimberly D Siegmund, Stephen S Hecht, Jian-Min Yuan, William J Blot, Daniel O Stram, Loïc Le Marchand, Sungshim L Park
The impact of tobacco exposure on health varies by race and ethnicity and is closely tied to internal nicotine dose, a marker of carcinogen uptake. DNA methylation is strongly responsive to smoking status and may mediate health effects, but study of associations with internal dose is limited. We performed a blood leukocyte epigenome-wide association study (EWAS) of urinary total nicotine equivalents (TNEs; a measure of nicotine uptake) and DNA methylation measured using the MethylationEPIC v1.0 BeadChip (EPIC) in six racial and ethnic groups across three cohort studies...
February 16, 2024: American Journal of Human Genetics
#27
JOURNAL ARTICLE
Yige Li, Jingwen Gong, Qingrong Sun, Eu Gene Vong, Xiaoqing Cheng, Binghong Wang, Ying Yuan, Li Jin, Eric R Gamazon, Dan Zhou, Maode Lai, Dandan Zhang
Genetic variants are involved in the orchestration of alternative polyadenylation (APA) events, while the role of DNA methylation in regulating APA remains unclear. We generated a comprehensive atlas of APA quantitative trait methylation sites (apaQTMs) across 21 different types of cancer (1,612 to 60,219 acting in cis and 4,448 to 142,349 in trans). Potential causal apaQTMs in non-cancer samples were also identified. Mechanistically, we observed a strong enrichment of cis-apaQTMs near polyadenylation sites (PASs) and both cis- and trans-apaQTMs in proximity to transcription factor (TF) binding regions...
February 9, 2024: American Journal of Human Genetics
#28
JOURNAL ARTICLE
James L Shepherdson, Katie Hutchison, Dilan Wellalage Don, George McGillivray, Tae-Ik Choi, Carolyn A Allan, David J Amor, Siddharth Banka, Donald G Basel, Laura D Buch, Deanna Alexis Carere, Renée Carroll, Jill Clayton-Smith, Ali Crawford, Morten Dunø, Laurence Faivre, Christopher P Gilfillan, Nina B Gold, Karen W Gripp, Emma Hobson, Alexander M Holtz, A Micheil Innes, Bertrand Isidor, Adam Jackson, Panagiotis Katsonis, Leila Amel Riazat Kesh, Sébastien Küry, François Lecoquierre, Paul Lockhart, Julien Maraval, Naomichi Matsumoto, Julie McCarrier, Josephine McCarthy, Noriko Miyake, Lip Hen Moey, Andrea H Németh, Elsebet Østergaard, Rushina Patel, Kate Pope, Jennifer E Posey, Rhonda E Schnur, Marie Shaw, Elliot Stolerman, Julie P Taylor, Erin Wadman, Emma Wakeling, Susan M White, Lawrence C Wong, James R Lupski, Olivier Lichtarge, Mark A Corbett, Jozef Gecz, Charles M Nicolet, Peggy J Farnham, Cheol-Hee Kim, Marwan Shinawi
Pathogenic variants in multiple genes on the X chromosome have been implicated in syndromic and non-syndromic intellectual disability disorders. ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not been characterized in association with disease. Here, we present clinical and molecular characterization of 18 individuals with germline ZFX variants. Exome or genome sequencing revealed 11 variants in 18 subjects (14 males and 4 females) from 16 unrelated families...
February 5, 2024: American Journal of Human Genetics
#29
JOURNAL ARTICLE
Jianhua Zhang, Mritunjay Pandey, Adam Awe, Nicole Lue, Claire Kittock, Emma Fikse, Katherine Degner, Jenna Staples, Neha Mokhasi, Weiping Chen, Yanqin Yang, Poorni Adikaram, Nirmal Jacob, Emily Greenfest-Allen, Rachel Thomas, Laura Bomeny, Yajun Zhang, Timothy J Petros, Xiaowen Wang, Yulong Li, William F Simonds
Disease-associated variants identified from genome-wide association studies (GWASs) frequently map to non-coding areas of the genome such as introns and intergenic regions. An exclusive reliance on gene-agnostic methods of genomic investigation could limit the identification of relevant genes associated with polygenic diseases such as Alzheimer disease (AD). To overcome such potential restriction, we developed a gene-constrained analytical method that considers only moderate- and high-risk variants that affect gene coding sequences...
February 3, 2024: American Journal of Human Genetics
#30
JOURNAL ARTICLE
Mai Eshel, Beatrice Milon, Ronna Hertzano, Ran Elkon
Age-related hearing loss (ARHL) is a major health concern among the elderly population. It is hoped that increasing our understanding of its underlying pathophysiological processes will lead to the development of novel therapies. Recent genome-wide association studies (GWASs) discovered a few dozen genetic variants in association with elevated risk for ARHL. Integrated analysis of GWAS results and transcriptomics data is a powerful approach for elucidating specific cell types that are involved in disease pathogenesis...
February 2, 2024: American Journal of Human Genetics
#31
JOURNAL ARTICLE
Caitlin G Allen, Kelly J Hunt, Lori L McMahon, Clay Thornhill, Amy Jackson, John T Clark, Katie Kirchoff, Kelli L Garrison, Kimberly Foil, Libby Malphrus, Samantha Norman, Paula S Ramos, Kelly Perritt, Caroline Brown, Leslie Lenert, Daniel P Judge
We use the implementation science framework RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) to describe outcomes of In Our DNA SC, a population-wide genomic screening (PWGS) program. In Our DNA SC involves participation through clinical appointments, community events, or at home collection. Participants provide a saliva sample that is sequenced by Helix, and those with a pathogenic variant or likely pathogenic variant for CDC Tier 1 conditions are offered free genetic counseling. We assessed key outcomes among the first cohort of individuals recruited...
February 1, 2024: American Journal of Human Genetics
#32
JOURNAL ARTICLE
Amy G Jones, Matilde Aquilino, Rory J Tinker, Laura Duncan, Zandra Jenkins, Gemma L Carvill, Stephanie J DeWard, Dorothy K Grange, M J Hajianpour, Benjamin J Halliday, Muriel Holder-Espinasse, Judit Horvath, Silvia Maitz, Vincenzo Nigro, Manuela Morleo, Victoria Paul, Careni Spencer, Alina I Esterhuizen, Tilman Polster, Alice Spano, Inés Gómez-Lozano, Abhishek Kumar, Gemma Poke, John A Phillips, Hunter R Underhill, Gregory Gimenez, Takashi Namba, Stephen P Robertson
Glutamine synthetase (GS), encoded by GLUL, catalyzes the conversion of glutamate to glutamine. GS is pivotal for the generation of the neurotransmitters glutamate and gamma-aminobutyric acid and is the primary mechanism of ammonia detoxification in the brain. GS levels are regulated post-translationally by an N-terminal degron that enables the ubiquitin-mediated degradation of GS in a glutamine-induced manner. GS deficiency in humans is known to lead to neurological defects and death in infancy, yet how dysregulation of the degron-mediated control of GS levels might affect neurodevelopment is unknown...
April 4, 2024: American Journal of Human Genetics
#33
JOURNAL ARTICLE
Sami Jalil, Timo Keskinen, Juhana Juutila, Rocio Sartori Maldonado, Liliya Euro, Anu Suomalainen, Risto Lapatto, Emilia Kuuluvainen, Ville Hietakangas, Timo Otonkoski, Mervi E Hyvönen, Kirmo Wartiovaara
Argininosuccinate lyase deficiency (ASLD) is a recessive metabolic disorder caused by variants in ASL. In an essential step in urea synthesis, ASL breaks down argininosuccinate (ASA), a pathognomonic ASLD biomarker. The severe disease forms lead to hyperammonemia, neurological injury, and even early death. The current treatments are unsatisfactory, involving a strict low-protein diet, arginine supplementation, nitrogen scavenging, and in some cases, liver transplantation. An unmet need exists for improved, efficient therapies...
April 4, 2024: American Journal of Human Genetics
#34
REVIEW
Kenneth E Westerman, Tamar Sofer
Despite the importance of gene-environment interactions (GxEs) in improving and operationalizing genetic discovery, interpretation of any GxEs that are discovered can be surprisingly difficult. There are many potential biological and statistical explanations for a statistically significant finding and, likewise, it is not always clear what can be claimed based on a null result. A better understanding of the possible underlying mechanisms leading to a detected GxE can help investigators decide which are and which are not relevant to their hypothesis...
April 4, 2024: American Journal of Human Genetics
#35
Maimuna S Paul, Sydney L Michener, Hongling Pan, Hiuling Chan, Jessica M Pfliger, Jill A Rosenfeld, Vanesa C Lerma, Alyssa Tran, Megan A Longley, Richard A Lewis, Monika Weisz-Hubshman, Mir Reza Bekheirnia, Nasim Bekheirnia, Lauren Massingham, Michael Zech, Matias Wagner, Hartmut Engels, Kirsten Cremer, Elisabeth Mangold, Sophia Peters, Jessica Trautmann, Claudia Perne, Jessica L Mester, Maria J Guillen Sacoto, Richard Person, Pamela P McDonnell, Stacey R Cohen, Laina Lusk, Ana S A Cohen, Jean-Baptiste Le Pichon, Tomi Pastinen, Dihong Zhou, Kendra Engleman, Caroline Racine, Laurence Faivre, Sébastien Moutton, Anne-Sophie Denommé-Pichon, Hyun Yong Koh, Annapurna Poduri, Jeffrey Bolton, Cordula Knopp, Dong Sun Julia Suh, Andrea Maier, Mehran Beiraghi Toosi, Ehsan Ghayoor Karimiani, Reza Maroofian, Gerald Bradley Schaefer, Vijayalakshmi Ramakumaran, Pradeep Vasudevan, Benito Banos-Pinero, Alistair T Pagnamenta, Chitra Prasad, Matthew Osmond, Sarah Schuhmann, Georgia Vasileiou, Sophie Russ-Hall, Ingrid E Scheffer, Gemma L Carvill, Heather Mefford, Carlos A Bacino, Brendan H Lee, Hsiao-Tuan Chao
No abstract text is available yet for this article.
April 4, 2024: American Journal of Human Genetics
#36
JOURNAL ARTICLE
Doug Speed, David M Evans
We propose TetraHer, a method for estimating the liability heritability of binary phenotypes. TetraHer has five key features. First, it can be applied to data from complex pedigrees that contain multiple types of relationships. Second, it can correct for ascertainment of cases or controls. Third, it can accommodate covariates. Fourth, it can model the contribution of common environment. Fifth, it produces a likelihood that can be used for significance testing. We first demonstrate the validity of TetraHer on simulated data...
April 4, 2024: American Journal of Human Genetics
#37
Derek J C Tai, Parisa Razaz, Serkan Erdin, Dadi Gao, Jennifer Wang, Xander Nuttle, Celine E de Esch, Ryan L Collins, Benjamin B Currall, Kathryn O'Keefe, Nicholas D Burt, Rachita Yadav, Lily Wang, Kiana Mohajeri, Tatsiana Aneichyk, Ashok Ragavendran, Alexei Stortchevoi, Elisabetta Morini, Weiyuan Ma, Diane Lucente, Alex Hastie, Raymond J Kelleher, Roy H Perlis, Michael E Talkowski, James F Gusella
No abstract text is available yet for this article.
March 7, 2024: American Journal of Human Genetics
#38
Saranya Balachandran, Cesar A Prada-Medina, Martin A Mensah, Juliane Glaser, Naseebullah Kakar, Inga Nagel, Jelena Pozojevic, Enrique Audain, Marc-Phillip Hitz, Martin Kircher, Varun K A Sreenivasan, Malte Spielmann
No abstract text is available yet for this article.
March 7, 2024: American Journal of Human Genetics
#39
JOURNAL ARTICLE
Nancy J Cox
This article is based on the address given by the author at the 2023 meeting of The American Society of Human Genetics (ASHG). A video of the original address can be found at the ASHG website.
March 7, 2024: American Journal of Human Genetics
#40
JOURNAL ARTICLE
Michael Boehnke
This article is based on the address given by the author at the 2023 meeting of the American Society of Human Genetics (ASHG) in Washington, D.C. The video of the original address can be found at the ASHG website.
March 7, 2024: American Journal of Human Genetics
Make the most of Read.
Download the mobile app.
Download the mobile app.
Fetching more papers... 
