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.

Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase
Start-loss variants in GLUL result in a severe developmental and epileptic phenotype through the stabilization of glutamine synthetase, an enzyme crucial for brain function. This disorder is unusual in its gain-of-stabilization mechanism contrasting with the allelic deficiency disorder. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - April 4, 2024 Category: Genetics & Stem Cells Authors: Amy G. Jones, Matilde Aquilino, Rory J. Tinker, Laura Duncan, Zandra Jenkins, Gemma L. Carvill, Stephanie J. DeWard, Dorothy K. Grange, MJ Hajianpour, Benjamin J. Halliday, Muriel Holder-Espinasse, Judit Horvath, Silvia Maitz, Vincenzo Nigro, Manuela Morl Tags: Article Source Type: research

Genetic and functional correction of argininosuccinate lyase deficiency using CRISPR adenine base editors
Harnessing CRISPR to correct a metabolic inherited disease, we developed a therapeutically relevant method to precisely edit the Finnish Founder pathogenic variant responsible for argininosuccinate lyase deficiency. By lipid-nanoparticle-mediated delivery of the adenosine base editor RNA, we achieve efficient gene editing and metabolic normalization in patient fibroblasts. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - April 4, 2024 Category: Genetics & Stem Cells Authors: Sami Jalil, Timo Keskinen, Juhana Juutila, Rocio Sartori Maldonado, Liliya Euro, Anu Suomalainen, Risto Lapatto, Emilia Kuuluvainen, Ville Hietakangas, Timo Otonkoski, Mervi E. Hyv önen, Kirmo Wartiovaara Tags: Article Source Type: research

Many roads to a gene-environment interaction
We describe five key phenomena, both “real” and spurious, that can produce a detectable GxE and discuss how researchers may plan experiments and interpret GxE findings and their clinical relevance in light of these phenomena. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - April 4, 2024 Category: Genetics & Stem Cells Authors: Kenneth E. Westerman, Tamar Sofer Tags: Review Source Type: research

This Month in The Journal
Although the detrimental effects of smoking on human health are well documented, our understanding of these effects at a molecular level remains incomplete. In recent years, many studies have identified associations between smoking and changes in DNA methylation, an epigenetic mark that modulates gene expression. Most of these analyses have utilized the most widely available biological sample: blood. In this issue, Li et  al. leverage data from the Genotype-Tissue Expression (GTEx) project to explore how smoking alters DNA methylation and gene expression across a range of tissues. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - April 4, 2024 Category: Genetics & Stem Cells Authors: Alyson B. Barnes, Kylee L. Spencer, Sara B. Cullinan Tags: Editors' Corner Source Type: research

De novo missense variants in exon 9 of SEPHS1 cause a neurodevelopmental condition with developmental delay, poor growth, hypotonia, and dysmorphic features
We report nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Our findings provide insight into the molecular pathogenesis of this neurodevelopmental disorder. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - March 25, 2024 Category: Genetics & Stem Cells Authors: Sureni V. Mullegama, Kaitlyn A. Kiernan, Erin Torti, Ethan Pavlovsky, Nicholas Tilton, Austin Sekula, Hua Gao, Joseph T. Alaimo, Kendra Engleman, Eric T. Rush, Karli Blocker, Katrina M. Dipple, Veronica M. Fettig, Heather Hare, Ian Glass, Dorothy K. Grang Tags: Report Source Type: research

Detection of elusive DNA copy-number variations in hereditary disease and cancer through the use of noncoding and off-target sequencing reads
Copy-number variations are a type of DNA variants that can lead to genetic disease and cancer. Because of important technical limitations, they are usually difficult to identify. We have created a software, OFF-PEAK, which makes use of data that are discarded by conventional procedures to efficiently detect these particular variants. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - March 25, 2024 Category: Genetics & Stem Cells Authors: Mathieu Quinodoz, Karolina Kaminska, Francesca Cancellieri, Ji Hoon Han, Virginie G. Peter, Elifnaz Celik, Lucas Janeschitz-Kriegl, Nils Sch ärer, Daniela Hauenstein, Bence György, Giacomo Calzetti, Vincent Hahaut, Sónia Custódio, Ana Cristina Sousa, Tags: Article Source Type: research

Biobank-scale inference of multi-individual identity by descent and gene conversion
We present a method for efficiently identifying clusters of identical-by-descent haplotypes in biobank-scale sequence data, and we demonstrate how these clusters can be used to identify alleles that have been changed by gene conversion. We apply our methods to UK Biobank sequence data. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - March 20, 2024 Category: Genetics & Stem Cells Authors: Sharon R. Browning, Brian L. Browning Tags: Article Source Type: research

A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3
(The American Journal of Human Genetics 111, 96 –118, January 4, 2024) (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - March 19, 2024 Category: Genetics & Stem Cells Authors: 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, Mich Tags: Correction Source Type: research

Population structure and migration in the Eastern Highlands of Papua New Guinea, a region impacted by the kuru epidemic
Explore an in-depth investigation of the Eastern Highlands of Papua New Guinea. Analyses attempt to disentangle the complex relationships between genetics, linguistics, and the clan system of political organization. Additionally, an analysis investigating the impact of the kuru epidemic on migration flows in the region is undertaken. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - March 19, 2024 Category: Genetics & Stem Cells Authors: Liam Quinn, Jerome Whitfield, Michael P. Alpers, Tracy Campbell, Holger Hummerich, William Pomat, Peter Siba, George Koki, Ida Moltke, John Collinge, Garrett Hellenthal, Simon Mead Tags: Article Source Type: research

Expanding the PRAAS spectrum: De novo mutations of immunoproteasome subunit β-type 10 in six infants with SCID-Omenn syndrome
This study highlights the identification of recurrent heterozygous de novo mutations in immunoproteasome subunit β2i (PSMB10) as a cause for SCID-Omenn syndrome. These variants are predicted to profoundly disrupt immunoproteasome structure and function, emphasizing its importance for lymphocyte development. Pathogenic variants in PSMB10 should be sought in SCID newborn screening. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - March 18, 2024 Category: Genetics & Stem Cells Authors: Caspar I. van der Made, Simone Kersten, Odelia Chorin, Karin R. Engelhardt, Gayatri Ramakrishnan, Helen Griffin, Ina Schim van der Loeff, Hanka Venselaar, Annick Raas Rothschild, Meirav Segev, Janneke H.M. Schuurs-Hoeijmakers, Tuomo Mantere, Rick Essers, Tags: Report Source Type: research

Mono-allelic KCNB2 variants lead to a neurodevelopmental syndrome caused by altered channel inactivation
In this study, we identify 10 variants in KCNB2 in individuals with neurodevelopmental disorders. Our data suggest that most KCNB2 variants show reduced potassium conductance due to either reduced functional expression or increased channel inactivation. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - March 18, 2024 Category: Genetics & Stem Cells Authors: Shreyas Bhat, Justine Rousseau, Coralie Michaud, Charles Marques Louren ço, Joan M. Stoler, Raymond J. Louie, Lola K. Clarkson, Angie Lichty, Daniel C. Koboldt, Shalini C. Reshmi, Sanjay M. Sisodiya, Eva M.M. Hoytema van Konijnenburg, Klaas Koop, Peter M Tags: Article Source Type: research

Estimating disease heritability from complex pedigrees allowing for ascertainment and covariates
TetraHer is a new method for estimating the heritability of diseases that allows for ascertainment of cases and for contributions of covariates. Applied to UK Biobank data, TetraHer finds 107 ICD-10 codes with significant heritability. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - March 14, 2024 Category: Genetics & Stem Cells Authors: Doug Speed, David M. Evans Tags: Article Source Type: research

The association of cigarette smoking with DNA methylation and gene expression in human tissue samples
Cigarette smoking adversely affects many aspects of human health, and epigenetic responses to smoking may reflect mechanisms that mediate or defend against these effects. Prior studies of smoking and DNA methylation (DNAm), typically measured in leukocytes, have identified numerous smoking-associated regions (e.g., AHRR). To identify smoking-associated DNAm features in typically inaccessible tissues, we generated array-based DNAm data for 916 tissue samples from the GTEx (Genotype-Tissue Expression) project representing 9 tissue types (lung, colon, ovary, prostate, blood, breast, testis, kidney, and muscle). (Source: The A...
Source: The American Journal of Human Genetics - March 14, 2024 Category: Genetics & Stem Cells Authors: James L. Li, Niyati Jain, Lizeth I. Tamayo, Lin Tong, Farzana Jasmine, Muhammad G. Kibriya, Kathryn Demanelis, Meritxell Oliva, Lin S. Chen, Brandon L. Pierce Tags: Article Source Type: research

De novo variants in FRYL are associated with developmental delay, intellectual disability, and dysmorphic features
We report fourteen individuals with de novo variants in FRYL who present with neurodevelopmental features. Nine variants correspond to premature stop codons, frameshifts, or splicing variants. Modeling in Drosophila supports an essential developmental function for the fly FRYL ortholog; genomic integration of three missense variants caused a loss-of-function phenotype. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - March 12, 2024 Category: Genetics & Stem Cells Authors: Xueyang Pan, Alice M. Tao, Shenzhao Lu, Mengqi Ma, Shabab B. Hannan, Rachel Slaugh, Sarah Drewes Williams, Lauren O'Grady, Oguz Kanca, Richard Person, Melissa T. Carter, Konrad Platzer, Franziska Schnabel, Rami Abou Jamra, Amy E. Roberts, Jane W. Newburge Tags: Article Source Type: research

Guidance on use of race, ethnicity, and geographic origin as proxies for genetic ancestry groups in biomedical publications
In March 2023, the National Academies of Sciences, Engineering, and Medicine (NASEM) released a consensus study report titled Using Population Descriptors in Genetics and Genomics Research.1 Sponsored by the US National Institutes of Health, the report is more than a discussion of the use of terminology; the authors of the NASEM report suggest a tectonic shift away from current models that use race, ethnicity, and geographic origin as proxies for genetic ancestry groups (i.e., a set of individuals who share more similar genetic ancestries) in genetic and genomic science. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - March 12, 2024 Category: Genetics & Stem Cells Authors: W. Gregory Feero, Robert D. Steiner, Anne Slavotinek, Tiago Faial, Michael J. Bamshad, Jehannine Austin, Bruce R. Korf, Annette Flanagin, Kirsten Bibbins-Domingo Tags: Editorial Source Type: research