The American Journal of Human Genetics 
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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.This Month in The Journal
Biobanks are becoming increasingly common, and although each has its own goals, strengths, and challenges, the standard recipe is a focus on scientific discovery through genetic data linked to electronic health records (EHRs). In this issue, Wiley et al. describe the development of the Colorado Center for Personalized Medicine Biobank (CCPM Biobank), which is not only designed to advance research but also to directly impact patient care. A few key elements were crucial to achieving these dual aims. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2024 Category: Genetics & Stem Cells Authors: Alyson B. Barnes, Kylee L. Spencer, Sara B. Cullinan Tags: Editors' Corner Source Type: research
75 years of The American Journal of Human Genetics
This past year, the American Society of Human Genetics (ASHG) celebrated its 75th anniversary. The American Journal of Human Genetics (AJHG) was founded one year after formation of the Society, so now in 2024, we recognize the 75th anniversary of AJHG. AJHG was conceived as the flagship of the Society to provide a home for publication of human genetics research, and the first edition was published in 1949. It has continued to serve this role three quarters of a century later, remaining a pre-eminent journal in our field even as innumerable other journals have embraced research in human genetics. (Source: The American Journ...
Source: The American Journal of Human Genetics - January 4, 2024 Category: Genetics & Stem Cells Authors: Bruce R. Korf Tags: Editorial Source Type: research
A Bayesian fine-mapping model using a continuous global-local shrinkage prior with applications in prostate cancer analysis
We develop a fine-mapping method, called h2-D2, utilizing a continuous global-local shrinkage prior, and propose an approach to define credible set of causal variants in this framework. Our proposed method outperforms the state-of-art fine-mapping methods based on discrete mixture priors. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 2, 2024 Category: Genetics & Stem Cells Authors: Xiang Li, Pak Chung Sham, Yan Dora Zhang Tags: Article Source Type: research
A recurrent de novo MAX p.Arg60Gln variant causes a syndromic overgrowth disorder through differential expression of c-Myc target genes
Harris et al. describe three individuals with overlapping macrocephaly-associated phenotypes carrying a recurrent de novo c.179G>A (p.Arg60Gln) variant in Myc-associated factor X (MAX). MAXArg60Gln binds its target E-box sequence with a lower affinity, meaning more efficient heterodimerization with c-Myc and dysregulated transcriptional activity. c-Myc inhibitors provide a possible therapeutic option for individuals carrying this variant. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 22, 2023 Category: Genetics & Stem Cells Authors: Erica L. Harris, Vincent Roy, Martin Montagne, Ailsa M.S. Rose, Helen Livesey, Margot R.F. Reijnders, Emma Hobson, Francis H. Sansbury, Marjolein H. Willemsen, Rolph Pfundt, Daniel Warren, Vernon Long, Ian M. Carr, Han G. Brunner, Eamonn G. Sheridan, Hele Tags: Article Source Type: research
Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome
Bi-allelic variants in the translational GTPases GTPBP1 and GTPBP2 may affect ribosomal translational control and impair brain development and neurological function. This research identifies 20 individuals with homozygous GTPBP1 and GTPBP2 variants leading to an identical neurodevelopmental syndrome, which we defined as “Gtpbp1/2-related ectodermal neurodevelopmental (GREND) syndrome.” (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 19, 2023 Category: Genetics & Stem Cells Authors: Vincenzo Salpietro, Reza Maroofian, Maha S. Zaki, Jamie Wangen, Andrea Ciolfi, Sabina Barresi, Stephanie Efthymiou, Angelique Lamaze, Gabriel N. Aughey, Fuad Al Mutairi, Aboulfazl Rad, Clarissa Rocca, Elisa Cal ì, Andrea Accogli, Federico Zara, Pasquale Tags: Report Source Type: research
A statistical method for image-mediated association studies discovers genes and pathways associated with four brain disorders
The authors developed a computational tool, the image-mediated association study (IMAS), which utilizes borrowed imaging/genomics data to conduct association mapping in legacy GWAS cohorts. A cerebellar-mediated mechanism was identified to be common to the four disorders. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 19, 2023 Category: Genetics & Stem Cells Authors: Jingni He, Lilit Antonyan, Harold Zhu, Karen Ardila, Qing Li, David Enoma, William Zhang, Andy Liu, Thierry Chekouo, Bo Cao, M. Ethan MacDonald, Paul D. Arnold, Quan Long Tags: Article Source Type: research
ClinGen guidance for use of the PP1/BS4 co-segregation and PP4 phenotype specificity criteria for sequence variant pathogenicity classification
The 2015 ACMG/AMP variant classification recommendations included pathogenic (PP1) and benign (BS4) criteria for co-segregation, but details for using them were sparse. We developed a points-based co-segregation heuristic and integrated the specific phenotype criterion (PP4). We also show that negative evidence at one locus constitutes positive evidence for other loci. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 15, 2023 Category: Genetics & Stem Cells Authors: Leslie G. Biesecker, Alicia B. Byrne, Steven M. Harrison, Tina Pesaran, Alejandro A. Sch äffer, Brian H. Shirts, Sean V. Tavtigian, Heidi L. Rehm, ClinGen Sequence Variant Interpretation Working Group Tags: Article Source Type: research
Systematic analysis of variants escaping nonsense-mediated decay uncovers candidate Mendelian diseases
We examined individuals with neurodevelopmental disorders referred for clinical exome sequencing for gene-level enrichment of de novo PTVesc and phenotypic similarity analysis. This analysis identified PTVesc as a mutation spectrum in established and candidate Mendelian disease-gene associations. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 12, 2023 Category: Genetics & Stem Cells Authors: Rebecca I. Torene, Maria J. Guillen Sacoto, Francisca Millan, Zhancheng Zhang, Stephen McGee, Matthew Oetjens, Elizabeth Heise, Karen Chong, Richard Sidlow, Lauren O ’Grady, Inderneel Sahai, Christa L. Martin, David H. Ledbetter, Scott M. Myers, Kevin J Tags: Article Source Type: research
Will variants of uncertain significance still exist in 2030?
The authors propose that many, if not most, variants of uncertain significance (VUSs) in coding regions will be resolved by 2030 and outline a confluence of changes making this possible. They note that achieving this goal will depend on the choices made now and in the next few years. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 11, 2023 Category: Genetics & Stem Cells Authors: Douglas M. Fowler, Heidi L. Rehm Tags: Perspective Source Type: research
Tree-based QTL mapping with expected local genetic relatedness matrices
We identify quantitative trait loci by testing the eGRM, a measure of local relatedness based on the ancestral recombination graph, for association with phenotypes using a variance-components framework. This is beneficial for phenotypes with allelic heterogeneity and allows us to capture untyped variation without imputation in understudied populations. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 7, 2023 Category: Genetics & Stem Cells Authors: Vivian Link, Joshua G. Schraiber, Caoqi Fan, Bryan Dinh, Nicholas Mancuso, Charleston W.K. Chiang, Michael D. Edge Tags: Article Source Type: research
Genomic medicine year in review: 2023
Starting in 2019, AJHG has published an annual feature1,2,3,4 identifying ten key advances in applying genomic information to clinical care that were reported in the previous 12 months of published literature. The Genomic Medicine Working Group of the National Advisory Council for Human Genome Research of the National Human Genome Research Institute (NHGRI) has authored these reviews, based on its broader effort to identify notable accomplishments in genomic medicine on a monthly basis and post them on a searchable website (https://www.genome.gov/health/Genomics-and-Medicine/accomplishments). (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 7, 2023 Category: Genetics & Stem Cells Authors: Teri A. Manolio, Jahnavi Narula, Carol J. Bult, Rex L. Chisholm, Patricia A. Deverka, Geoffrey S. Ginsburg, Eric D. Green, Gillian Hooker, Gail P. Jarvik, George A. Mensah, Erin M. Ramos, Dan M. Roden, Robb Rowley, Marc S. Williams Tags: Year in review Source Type: research
H. Eldon Sutton, PhD (1927 –2023): A long and full life
Eldon Sutton, professor emeritus at University of Texas at Austin passed away on June 20, 2023 in Austin, TX at the age of 96. Beverly, his wife of 61 years, predeceased him by four months in February 2023. His daughters, Susan and Caroline, and two granddaughters survive him. Eldon was the epitome of a Texas gentleman, tall and erudite, calm and soft spoken, with no trace of accent to show his Texas roots. He was at the forefront of human genetics in many respects. He was on the faculty at the University of Michigan ’s newly formed Department of Genetics in 1956 with Jim Neel. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 7, 2023 Category: Genetics & Stem Cells Authors: Barbara R. DuPont, Roberta Palmour, Patricia Howard-Peebles, Chih-Lin Hsieh Tags: Obituary Source Type: research
This month in The Journal
In individuals with phenylketonuria (PKU), the most common inborn error of metabolism, phenylanine (Phe) accumulates to neurotoxic levels as a result of the body ’s inability to convert Phe to tyrosine. PKU is caused by mutations in PAH, the gene encoding phenylalanine hydroxylase, and the most commonly occurring pathogenic PAH variant worldwide is c.1222C>T. Individuals with this variant do not respond to current pharmacological treatments for PKU; a one-time therapy that permanently normalizes blood Phe levels could be transformative for the care of these individuals. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - December 7, 2023 Category: Genetics & Stem Cells Authors: Alyson B. Barnes, Kylee L. Spencer, Sara B. Cullinan Tags: Editors' Corner Source Type: research
Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease
In five families from Sk åne region in Sweden, expanded repeat expansions in ZFHX3 were identified as the cause for spinocerebellar ataxia type 4, SCA4. SCA4 is an autosomal-dominant disorder with progressive gait and balance disturbance and dyscoordination of movements. SCA4 might compromise nerves controlling automatic b odily functions. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 29, 2023 Category: Genetics & Stem Cells Authors: Joel Wallenius, Efthymia Kafantari, Emma Jhaveri, Sorina Gorcenco, Adam Ameur, Christin Karremo, Sigurd Dobloug, Kristina Karrman, Tom de Koning, Andreea Ilinca, Maria Landqvist Wald ö, Andreas Arvidsson, Staffan Persson, Elisabet Englund, Hans Ehrencron Tags: Article Source Type: research
Identifying risk variants for embryo aneuploidy using ultra-low coverage whole-genome sequencing from preimplantation genetic testing
Egg aneuploidy is common in human meiosis and is the primary cause of early miscarriage. Here, we developed a method to analyze ultra-low coverage whole-genome sequencing (ulc-WGS) data from preimplantation genetic testing for aneuploidy (PGT-A) of embryos and identified variants in CCDC66 associated with aneuploid conception risk. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - November 28, 2023 Category: Genetics & Stem Cells Authors: Siqi Sun, Mansour Aboelenain, Daniel Ariad, Mary E. Haywood, Charles R. Wageman, Marlena Duke, Aishee Bag, Manuel Viotti, Mandy Katz-Jaffe, Rajiv C. McCoy, Karen Schindler, Jinchuan Xing Tags: Article Source Type: research
