The American Journal of Human Genetics This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Improved detection of aberrant splicing with FRASER 2.0 and the intron Jaccard index
Detection of aberrantly spliced genes is an important step in RNA-seq-based rare-disease diagnostics. We recently developed FRASER, a denoising autoencoder-based method that outperformed alternative methods of detecting aberrant splicing. However, because FRASER ’s three splice metrics are partially redundant and tend to be sensitive to sequencing depth, we introduce here a more robust intron-excision metric, the intron Jaccard index, that combines the alternative donor, alternative acceptor, and intron-retention signal into a single value. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 24, 2023 Category: Genetics & Stem Cells Authors: Ines F. Scheller, Karoline Lutz, Christian Mertes, Vicente A. Y épez, Julien Gagneur Tags: Article Source Type: research

The NYCKidSeq randomized controlled trial: Impact of GU ÍA digitally enhanced genetic results disclosure in diverse families
GU ÍA, a digital application designed to enhance the delivery of genetic/genomic test results, was evaluated through the NYCKidSeq randomized controlled trial. Findings from the trial demonstrate that GUÍA positively impacts perceived and objective understanding of genetic results in diverse, multili ngual parents/guardians of children with suspected genetic conditions who underwent testing. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 24, 2023 Category: Genetics & Stem Cells Authors: Sabrina A. Suckiel, Nicole R. Kelly, Jacqueline A. Odgis, Katie M. Gallagher, Monisha Sebastin, Katherine E. Bonini, Priya N. Marathe, Kaitlyn Brown, Miranda Di Biase, Michelle A. Ramos, Jessica E. Rodriguez, Laura Scarimbolo, Beverly J. Insel, Kathleen D Tags: Article Source Type: research

CHARR efficiently estimates contamination from DNA sequencing data
Lu et  al. develop CHARR, a method for estimating DNA sample contamination from variant call data, which leverages the infiltration of reference reads within homozygous alternate variant calls. CHARR accurately recapitulates results from existing tools with substantially reduced cost and increased effici ency, which facilitates downstream analyses of ultra-large genomic data. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 23, 2023 Category: Genetics & Stem Cells Authors: Wenhan Lu, Laura D. Gauthier, Timothy Poterba, Edoardo Giacopuzzi, Julia K. Goodrich, Christine R. Stevens, Daniel King, Mark J. Daly, Benjamin M. Neale, Konrad J. Karczewski Tags: Article Source Type: research

Increasing diversity of functional genetics studies to advance biological discovery and human health
There is a dearth of genetic and environmental diversity in functional genomics datasets. Research focused on the variant-to-function gap aims to identify molecular QTLs but lacks data from non-European-ancestry populations. We discuss the major barriers and pose actionable suggestions, which aim to empower research and researchers from underserved populations. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 22, 2023 Category: Genetics & Stem Cells Authors: Sophia H.L. George, Alejandra Medina-Rivera, Youssef Idaghdour, Tuuli Lappalainen, Irene Gallego Romero Tags: Perspective Source Type: research

Assortative mating and parental genetic relatedness contribute to the pathogenicity of variably expressive variants
Many rare genetic variants are variably expressive, conferring risk for a range of clinical features with incomplete penetrance. We implicate assortative mating as a risk factor for disease in families carrying these variants by increasing genetic disease liability over generations, leading to the “genetic anticipation” observed in these families. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 17, 2023 Category: Genetics & Stem Cells Authors: Corrine Smolen, Matthew Jensen, Lisa Dyer, Lucilla Pizzo, Anastasia Tyryshkina, Deepro Banerjee, Laura Rohan, Emily Huber, Laila El Khattabi, Paolo Prontera, Jean-Hubert Caberg, Anke Van Dijck, Charles Schwartz, Laurence Faivre, Patrick Callier, Anne-Laur Tags: Article Source Type: research

Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome
Pathogenic variants in the spliceosome component WBP4 cause a severe neurodevelopmental disorder, expanding our understanding of spliceosome-related conditions. This research identifies ten individuals with five distinct homozygous loss-of-function WBP4 variants. This discovery reveals symptoms related to splicing targets of WBP4, shedding light on how abnormal splicing contributes to the disease. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 13, 2023 Category: Genetics & Stem Cells Authors: Eden Engal, Kaisa Teele Oja, Reza Maroofian, Ophir Geminder, Thuy-Linh Le, Pauline Marzin, Anne Guimier, Evyatar Mor, Naama Zvi, Naama Elefant, Maha S. Zaki, Joseph G. Gleeson, Kai Muru, Sander Pajusalu, Monica H. Wojcik, Divya Pachat, Marwa Abd Elmaksoud Tags: Report Source Type: research

Inferring disease architecture and predictive ability with LDpred2-auto
This study extends the utility of LDpred2-auto, a widely used method for deriving predictive polygenic scores. It validates the use of the latest version of LDpred2-auto for inferring key genetic parameters that inform us about the genetic architecture of traits, for identifying causal genetic variants, and for estimating predictive performance. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 8, 2023 Category: Genetics & Stem Cells Authors: Florian Priv é, Clara Albiñana, Julyan Arbel, Bogdan Pasaniuc, Bjarni J. Vilhjálmsson Tags: Article Source Type: research

RAB1A haploinsufficiency phenocopies the 2p14 –p15 microdeletion and is associated with impaired neuronal differentiation
We identify a dominant RAB1A-related neurocognitive disorder with speech and motor delay caused by loss-of-function and dominant-negative mutations in RAB1A. We demonstrate an essential role for RAB1A in neuronal arborization and implicate RAB1A haploinsufficiency in the pathogenesis of neurocognitive manifestations associated with the 2p14 –p15 microdeletion syndrome. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 3, 2023 Category: Genetics & Stem Cells Authors: Jonathan J. Rios, Yang Li, Nandina Paria, Ryan J. Bohlender, Chad Huff, Jill A. Rosenfeld, Pengfei Liu, Weimin Bi, Kentaro Haga, Mitsunori Fukuda, Shayal Vashisth, Kiran Kaur, Maria H. Chahrour, Michael B. Bober, Angela L. Duker, Farah A. Ladha, Neil A. H Tags: Report Source Type: research

Efficient in  vivo prime editing corrects the most frequent phenylketonuria variant, associated with high unmet medical need
The PAH c.1222C>T variant is the most frequent variant reported in phenylketonuria (PKU) individuals. Here, the authors show these individuals have poor metabolic control, and they use prime editing, delivered by adeno-associated viral vectors, to directly correct the variant in the liver in humanized PKU mice and definitively treat the disease. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 3, 2023 Category: Genetics & Stem Cells Authors: Dominique L. Brooks, Madelynn N. Whittaker, Ping Qu, Kiran Musunuru, Rebecca C. Ahrens-Nicklas, Xiao Wang Tags: Article Source Type: research

Response to Luzzatto et  al.
To the editor: In the last few years, updates to G6PD variant interpretation and drug use guidelines have been published, highlighting the importance and continued interest in connecting G6PD variation with G6PD deficiency, chronic anemia, and risk of adverse drug reactions. However, many challenges remain for G6PD variant interpretation, including those raised by Luzzatto et  al.1 (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 2, 2023 Category: Genetics & Stem Cells Authors: Renee C. Geck, Nicholas R. Powell, Maitreya J. Dunham Tags: Letter to the Editor Source Type: research

Potentially pathogenic and pathogenic G6PD variants
In their interesting and comprehensive paper in the February 2, 2023 issue of this journal, Geck et  al.1 have illustrated several aspects of genetic variation at the X-linked G6PD locus that is rather unique in terms of its clinical and public health implications. Their analysis supports the recently revised WHO classification: this is gratifying and not surprising, since the WHO revision was ca rried out after long deliberation, based in large part on recently reviewed data2,3 that Geck et al.1 have also analyzed. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 2, 2023 Category: Genetics & Stem Cells Authors: Lucio Luzzatto, Caterina Nannelli, Rosario Notaro Tags: Letter to the editor Source Type: research

Factorizing polygenic epistasis improves prediction and uncovers biological pathways in complex traits
Epistasis has been difficult to study in complex traits due to the statistical challenges of fitting polygenic interactions. Here, we develop a model called Epistasis Factor Analysis and demonstrate its utility for modeling epistasis effects in complex traits. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 2, 2023 Category: Genetics & Stem Cells Authors: David Tang, Jerome Freudenberg, Andy Dahl Tags: Article Source Type: research

The GenoVA study: Equitable implementation of a pragmatic randomized trial of polygenic-risk scoring in primary care
The Genomic Medicine at Veterans Affairs (GenoVA) Study is addressing three main challenges to the clinical implementation of PRS in preventive care: defining and determining their clinical utility, implementing them in time-constrained primary care settings, and countering their potential to exacerbate healthcare disparities. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 2, 2023 Category: Genetics & Stem Cells Authors: Jason L. Vassy, Charles A. Brunette, Matthew S. Lebo, Katharine MacIsaac, Thomas Yi, Morgan E. Danowski, Nicholas V.J. Alexander, Mark P. Cardellino, Kurt D. Christensen, Manish Gala, Robert C. Green, Elizabeth Harris, Natalie E. Jones, Benjamin J. Kerman Tags: Perspective Source Type: research

Envisioning a new era: Complete genetic information from routine, telomere-to-telomere genomes
In the next decade, advancements in long-read sequencing technologies will facilitate widespread access to complete, haplotype-phased genome assemblies. This will significantly enhance variant discovery, understanding of genetic diversity, and epigenetic characterization, transforming the field of human genetics and our approach to associating genetic variations with diseases. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 2, 2023 Category: Genetics & Stem Cells Authors: Karen H. Miga, Evan E. Eichler Tags: Perspective Source Type: research

To boldly go: Unpacking the NHGRI ’s bold predictions for human genomics by 2030
The 2020 strategic vision for human genomics, written by the National Human Genome Research Institute (NHGRI), was punctuated by a set of provocatively audacious “bold predictions for human genomics by 2030.” Starting here, these will be unpacked and discussed in an upcoming series in the American Journal of Human Genetics. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 2, 2023 Category: Genetics & Stem Cells Authors: Chris Gunter, Eric D. Green Tags: Forum Source Type: research