{"id":33149,"date":"2025-11-13T00:25:36","date_gmt":"2025-11-13T00:25:36","guid":{"rendered":"https:\/\/naijaglobalnews.org\/?p=33149"},"modified":"2025-11-13T00:25:36","modified_gmt":"2025-11-13T00:25:36","slug":"gregor-accelerating-genomics-for-rare-diseases","status":"publish","type":"post","link":"https:\/\/naijaglobalnews.org\/?p=33149","title":{"rendered":"GREGoR: accelerating genomics for rare diseases"},"content":{"rendered":"

\n<\/p>\n

  • \n

    Baxter, S. M. et al. Centers for Mendelian Genomics: a decade of facilitating gene discovery. Genet. Med. 24, 784\u2013797 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Taylor, J. C. et al. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders. Nat. Genet. 47, 717\u2013726 (2015).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wright, C. F. et al. Genomic diagnosis of rare pediatric disease in the United Kingdom and Ireland. N. Engl. J. Med. 388, 1559\u20131571 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rimmer, A. et al. Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications. Nat. Genet. 46, 912\u2013918 (2014).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Monaco, L. et al. Research on rare diseases: ten years of progress and challenges at IRDiRC. Nat. Rev. Drug Discov. 21, 319\u2013320 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Yang, Y. et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 312, 1870\u20131879 (2014).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Farnaes, L. et al. Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization. npj Genom. Med. 3, 10 (2018).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Posey, J. E. et al. Resolution of disease phenotypes resulting from multilocus genomic variation. N. Engl. J. Med. 376, 21\u201331 (2017). Multilocus genomic diagnoses occur in nearly 5% of solved exome cases, underscoring the complexity and need for comprehensive interpretation in rare disease phenotypes.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Turro, E. et al. Whole-genome sequencing of patients with rare diseases in a national health system. Nature 583, 96\u2013102 (2020).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bamshad, M. J. et al. The Centers for Mendelian Genomics: a new large-scale initiative to identify the genes underlying rare Mendelian conditions. Am. J. Med. Genet. A 158A, 1523\u20131525 (2012).<\/p>\n

    PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Posey, J. E. et al. Insights into genetics, human biology and disease gleaned from family based genomic studies. Genet. Med. 21, 798\u2013812 (2019).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chong, J. X. et al. The genetic basis of Mendelian phenotypes: discoveries, challenges, and opportunities. Am. J. Hum. Genet. 97, 199\u2013215 (2015).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Surl, D. et al. Clinician-driven reanalysis of exome sequencing data from patients with inherited retinal diseases. JAMA Netw. Open 7, e2414198 (2024).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Seaby, E. G. et al. A gene pathogenicity tool \u2018GenePy\u2019 identifies missed biallelic diagnoses in the 100,000 Genomes Project. Genet. Med. 26, 101073 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Liu, P. et al. Reanalysis of clinical exome sequencing data. N. Engl. J. Med. 380, 2478\u20132480 (2019). Systematic reanalysis of clinical exome data substantially increased diagnostic yield and was driven by the newest novel disease gene discoveries.<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Berger, S. I. et al. Increased diagnostic yield from negative whole genome-slice panels using automated reanalysis. Clin. Genet. 104, 377\u2013383 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wenger, A. M., Guturu, H., Bernstein, J. A. & Bejerano, G. Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers. Genet. Med. 19, 209\u2013214 (2017).<\/p>\n

    PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Weisburd, B. et al. Diagnosing missed cases of spinal muscular atrophy in genome, exome, and panel sequencing data sets. Genet. Med. 27, 101336 (2025).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Guo, M. H. et al. Inferring compound heterozygosity from large-scale exome sequencing data. Nat. Genet. 56, 152\u2013161 (2024). This work presents a method to infer phasing of rare variant pairs in short-read exomes using gnomAD, enabling improved diagnosis of recessive Mendelian conditions.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gudmundsson, S. et al. Variant interpretation using population databases: lessons from gnomAD. Hum. Mutat. 43, 1012\u20131030 (2022).<\/p>\n

    PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mitani, T. et al. High prevalence of multilocus pathogenic variation in neurodevelopmental disorders in the Turkish population. Am. J. Hum. Genet. 108, 1981\u20132005 (2021).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lemire, G. et al. Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease. Am. J. Hum. Genet. 111, 863\u2013876 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Du, H. et al. HMZDupFinder: a robust computational approach for detecting intragenic homozygous duplications from exome sequencing data. Nucleic Acids Res. 52, e18 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Babadi, M. et al. GATK-gCNV enables the discovery of rare copy number variants from exome sequencing data. Nat. Genet. 55, 1589\u20131597 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Du, H. et al. VizCNV: An integrated platform for concurrent phased BAF and CNV analysis with trio genome sequencing data. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.10.27.620363 (2024).<\/p>\n<\/li>\n

  • \n

    Wojcik, M. H. et al. Beyond the exome: what\u2019s next in diagnostic testing for Mendelian conditions. Am. J. Hum. Genet. 110, 1229\u20131248 (2023). Offers a roadmap for diagnostic escalation beyond exome sequencing, including RNA-seq, genome sequencing, and long-read technologies, essential for solving unsolved Mendelian cases.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Sudmant, P. H. et al. An integrated map of structural variation in 2,504 human genomes. Nature 526, 75\u201381 (2015).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Collins, R. L. et al. A structural variation reference for medical and population genetics. Nature 581, 444\u2013451 (2020).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Byrska-Bishop, M. et al. High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios. Cell 185, 3426\u20133440 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Collins, R. L. et al. Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome. Genome Biol. 18, 36 (2017).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wojcik, M. H. et al. Genome sequencing for diagnosing rare diseases. N. Engl. J. Med. 390, 1985\u20131997 (2024). Genome sequencing provided unique diagnoses in 8% of previously unsolved cases.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434\u2013443 (2020).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Vitsios, D., Dhindsa, R. S., Middleton, L., Gussow, A. B. & Petrovski, S. Prioritizing non-coding regions based on human genomic constraint and sequence context with deep learning. Nat. Commun. 12, 1504 (2021).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chen, S. et al. A genomic mutational constraint map using variation in 76,156 human genomes. Nature 625, 92\u2013100 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhang, X. et al. Genetic constraint at single amino acid resolution in protein domains improves missense variant prioritisation and gene discovery. Genome Med. 16, 88 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chao, K. R. et al. The landscape of regional missense mutational intolerance quantified from 125,748 exomes. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.04.11.588920 (2024).<\/p>\n<\/li>\n

  • \n

    Saad, A. K. et al. Biallelic in-frame deletion in TRAPPC4 in a family with developmental delay and cerebellar atrophy. Brain J. Neurol. 143, e83 (2020).<\/p>\n

    \n Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dawood, M. et al. A biallelic frameshift indel in PPP1R35 as a cause of primary microcephaly. Am. J. Med. Genet. A 191, 794\u2013804 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dardas, Z. et al. NODAL variants are associated with a continuum of laterality defects from simple D-transposition of the great arteries to heterotaxy. Genome Med. 16, 53 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Miller, D. E. et al. Targeted long-read sequencing identifies a retrotransposon insertion as a cause of altered GNAS Exon A\/B methylation in a family with autosomal dominant pseudohypoparathyroidism type 1b (PHP1B). J. Bone Miner. Res. 37, 1711\u20131719 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mori, T. et al. CFAP47 is implicated in X-linked polycystic kidney disease. Kidney Int. Rep. 9, 3580\u20133591 (2024).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bruels, C. C. et al. Diagnostic capabilities of nanopore long-read sequencing in muscular dystrophy. Ann. Clin. Transl. Neurol. 9, 1302\u20131309 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chen, X. et al. Genome-wide profiling of highly similar paralogous genes using HiFi sequencing. Nat. Commun. 16, 2340 (2025).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Negi, S. et al. Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection. Am. J. Hum. Genet. 112, 428\u2013449 (2025).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mahmoud, M. et al. Closing the gap: solving complex medically relevant genes at scale. Preprint at medRxiv https:\/\/doi.org\/10.1101\/2024.03.14.24304179 (2024).<\/p>\n<\/li>\n

  • \n

    Dias, K.-R. et al. Narrowing the diagnostic gap: genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort. Genet. Med. 26, 101076 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bilgrav Saether, K. et al. Leveraging the T2T assembly to resolve rare and pathogenic inversions in reference genome gaps. Genome Res. 34, 1785\u20131797 (2024).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Fu, Y. et al. MethPhaser: methylation-based long-read haplotype phasing of human genomes. Nat. Commun. 15, 5327 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    LaFlamme, C. W. et al. Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement. Nat. Commun. 15, 6524 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zheng, X. et al. STIX: long-reads based accurate structural variation annotation at population scale. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.09.30.615931 (2024).<\/p>\n<\/li>\n

  • \n

    Smolka, M. et al. Detection of mosaic and population-level structural variants with Sniffles2. Nat. Biotechnol. 42, 1571\u20131580 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Sedlazeck, F. J. et al. Accurate detection of complex structural variations using single-molecule sequencing. Nat. Methods 15, 461\u2013468 (2018).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Stergachis, A. B., Debo, B. M., Haugen, E., Churchman, L. S. & Stamatoyannopoulos, J. A. Single-molecule regulatory architectures captured by chromatin fiber sequencing. Science 368, 1449\u20131454 (2020).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Jha, A. et al. DNA-m6A calling and integrated long-read epigenetic and genetic analysis with fibertools. Genome Res. 34, 1976\u20131986 (2024).<\/p>\n<\/li>\n

  • \n

    Vollger, M. R. et al. Synchronized long-read genome, methylome, epigenome and transcriptome profiling resolve a Mendelian condition. Nat. Genet. 57, 469\u2013479 (2025). By integrating long-read genome, methylome, epigenome, and transcriptome data, this study demonstrates how complex, multi-mechanism rare diseases can be mechanistically resolved in a single assay.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Grasberger, H. et al. STR mutations on chromosome 15q cause thyrotropin resistance by activating a primate-specific enhancer of MIR7-2\/MIR1179. Nat. Genet. 56, 877\u2013888 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Carvalho, C. M. B. et al. Interchromosomal template-switching as a novel molecular mechanism for imprinting perturbations associated with Temple syndrome. Genome Med. 11, 25 (2019).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Jensen, T. D. et al. Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease. Genome Res. 35, 914\u2013928 (2025).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Pais, L. S. et al. seqr: a web-based analysis and collaboration tool for rare disease genomics. Hum. Mutat. 43, 698\u2013707 (2022).<\/p>\n

    PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lansdon, L. A. et al. Factors affecting migration to GRCh38 in laboratories performing clinical next-generation sequencing. J. Mol. Diagn. 23, 651\u2013657 (2021).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Li, H. et al. Exome variant discrepancies due to reference-genome differences. Am. J. Hum. Genet. 108, 1239\u20131250 (2021). Discrepancies between GRCh37 and GRCh38 reference genomes affect variant calling in around 200 genes including Mendelian disease genes.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ungar, R. A. et al. Impact of genome build on RNA-seq interpretation and diagnostics. Am. J. Hum. Genet. 111, 1282\u20131300 (2024). Genome build choice significantly alters RNA-seq interpretation across >2800 genes, directly impacting transcriptomics-guided rare disease diagnostics.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Behera, S. et al. FixItFelix: improving genomic analysis by fixing reference errors. Genome Biol. 24, 31 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wagner, J. et al. Curated variation benchmarks for challenging medically relevant autosomal genes. Nat. Biotechnol. 40, 672\u2013680 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Liao, W.-W. et al. A draft human pangenome reference. Nature 617, 312\u2013324 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Behera, S. et al. Comprehensive genome analysis and variant detection at scale using DRAGEN. Nat. Biotechnol. 43, 1177\u20131191 (2025). The DRAGEN pipeline is a high-accuracy, scalable variant detection method that leverages multigenome mapping and machine learning to identify all major variant types\u2014including single-nucleotide variants, copy-number variants, structural variants and short tandem repeats\u2014across diverse populations.<\/p>\n<\/li>\n

  • \n

    Chin, C.-S. et al. A pan-genome approach to decipher variants in the highly complex tandem repeat of LPA. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2022.06.08.495395 (2022).<\/p>\n<\/li>\n

  • \n

    Samocha, K. E. et al. A framework for the interpretation of de novo mutation in human disease. Nat. Genet. 46, 944\u2013950 (2014). A framework to evaluate de novo mutations improves gene discovery in rare diseases by distinguishing pathogenic mutations from background variation.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lupski, J. R., Belmont, J. W., Boerwinkle, E. & Gibbs, R. A. Clan genomics and the complex architecture of human disease. Cell 147, 32\u201343 (2011). Describes the foundational framework for emphasizing the role of recent, rare, and private variants in disease risk and highlights the importance of family-centric rare disease analysis.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Teran, N. A. et al. Nonsense-mediated decay is highly stable across individuals and tissues. Am. J. Hum. Genet. 108, 1401\u20131408 (2021).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Coban-Akdemir, Z. et al. Identifying genes whose mutant transcripts cause dominant disease traits by potential gain-of-function alleles. Am. J. Hum. Genet. 103, 171\u2013187 (2018).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Valencia, A. M. et al. Landscape of mSWI\/SNF chromatin remodeling complex perturbations in neurodevelopmental disorders. Nat. Genet. 55, 1400\u20131412 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Paine, I. et al. Paralog studies augment gene discovery: DDX and DHX genes. Am. J. Hum. Genet. 105, 302\u2013316 (2019).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gillentine, M. A. et al. Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders. Genome Med. 13, 63 (2021).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Amberger, J. S., Bocchini, C. A., Scott, A. F. & Hamosh, A. OMIM.org: leveraging knowledge across phenotype-gene relationships. Nucleic Acids Res. 47, D1038\u2013D1043 (2019).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    DiStefano, M. T. et al. The gene curation coalition: a global effort to harmonize gene-disease evidence resources. Genet. Med. 24, 1732\u20131742 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ochoa, S. et al. A deep intronic splice-altering AIRE variant causes APECED syndrome through antisense oligonucleotide-targetable pseudoexon inclusion. Sci. Transl. Med. 16, eadk0845 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wu, N. et al. TBX6 null variants and a common hypomorphic allele in congenital scoliosis. N. Engl. J. Med. 372, 341\u2013350 (2015).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lord, J. et al. Non-coding variants are a rare cause of recessive developmental disorders in trans with coding variants. Genet. Med. 26, 101249 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mao, K. et al. FOXI3 pathogenic variants cause one form of craniofacial microsomia. Nat. Commun. 14, 2026 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ganesh, V. S. et al. Neurodevelopmental disorder caused by deletion of CHASERR, a lncRNA gene. N. Engl. J. Med. 391, 1511\u20131518 (2024). Discovery of a neurodevelopmental disorder caused by CHASERR long non-coding deletion reveals regulatory non-coding elements as critical contributors to rare disease pathogenesis.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Greene, D. et al. Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders. Nat. Med. 30, 2165\u20132169 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chen, Y. et al. De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome. Nature 632, 832\u2013840 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Greene, D. et al. Mutations in the small nuclear RNA gene RNU2-2 cause a severe neurodevelopmental disorder with prominent epilepsy. Nat. Genet. 57, 1367\u20131373 (2025).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Nava, C. et al. Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption. Nat. Genet. 57, 1374\u20131388 (2025).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bozkurt-Yozgatli, T. et al. Multilocus pathogenic variants contribute to intrafamilial clinical heterogeneity: a retrospective study of sibling pairs with neurodevelopmental disorders. BMC Med. Genom. 17, 85 (2024).<\/p>\n

    CAS\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Liu, P. et al. An organismal CNV mutator phenotype restricted to early human development. Cell 168, 830\u2013842 (2017).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Du, H. et al. The multiple de novo copy number variant (MdnCNV) phenomenon presents with peri-zygotic DNA mutational signatures and multilocus pathogenic variation. Genome Med. 14, 122 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Logsdon, G. A. et al. Complex genetic variation in nearly complete human genomes. Nature 644, 430\u2013441 (2025).<\/p>\n<\/li>\n

  • \n

    Ebert, P. et al. Haplotype-resolved diverse human genomes and integrated analysis of structural variation. Science 372, eabf7117 (2021).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Grochowski, C. M. et al. Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci. Cell Genom. 4, 100590 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dardas, Z. et al. Genomic balancing act: deciphering DNA rearrangements in the complex chromosomal aberration involving 5p15.2, 2q31.1, and 18q21.32. Eur. J. Hum. Genet. 33, 231\u2013238 (2025).<\/p>\n<\/li>\n

  • \n

    Pehlivan, D. et al. Structural variant allelic heterogeneity in MECP2 duplication syndrome provides insight into clinical severity and variability of disease expression. Genome Med. 16, 146 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Jakubosky, D. et al. Discovery and quality analysis of a comprehensive set of structural variants and short tandem repeats. Nat. Commun. 11, 2928 (2020).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Jakubosky, D. et al. Properties of structural variants and short tandem repeats associated with gene expression and complex traits. Nat. Commun. 11, 2927 (2020).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dolzhenko, E. et al. Characterization and visualization of tandem repeats at genome scale. Nat. Biotechnol. 42, 1606\u20131614 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    English, A. C. et al. Analysis and benchmarking of small and large genomic variants across tandem repeats. Nat. Biotechnol. 43, 431\u2013442 (2025).<\/p>\n<\/li>\n

  • \n

    Dolzhenko, E. et al. REViewer: haplotype-resolved visualization of read alignments in and around tandem repeats. Genome Med. 14, 84 (2022).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Behera, S. et al. Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk. BMC Med. Genom. 17, 255 (2024).<\/p>\n

    CAS\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Weisburd, B., Tiao, G. & Rehm, H. L. Insights from a genome-wide truth set of tandem repeat variation. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2023.05.05.539588 (2023).<\/p>\n<\/li>\n

  • \n

    Cui, Y. et al. A genome-wide spectrum of tandem repeat expansions in 338,963 humans. Cell 187, 2336\u20132341 (2024). This study establishes a biobank-scale, population reference of tandem repeat expansions across ancestries from short-read genome sequencing.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Weisburd, B. et al. Defining a tandem repeat catalog and variation clusters for genome-wide analyses and population databases. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.10.04.615514 (2024).<\/p>\n<\/li>\n

  • \n

    Wang, Q. et al. Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes. Nat. Commun. 11, 2539 (2020).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Srinivasan, S. et al. Misannotated multi-nucleotide variants in public cancer genomics datasets lead to inaccurate mutation calls with significant implications. Cancer Res. 81, 282\u2013288 (2021).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Campbell, I. M. et al. Multiallelic positions in the human genome: challenges for genetic analyses. Hum. Mutat. 37, 231\u2013234 (2016).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lindeboom, R. G. H., Vermeulen, M., Lehner, B. & Supek, F. The impact of nonsense-mediated mRNA decay on genetic disease, gene editing and cancer immunotherapy. Nat. Genet. 51, 1645\u20131651 (2019).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lindeboom, R. G. H., Supek, F. & Lehner, B. The rules and impact of nonsense-mediated mRNA decay in human cancers. Nat. Genet. 48, 1112\u20131118 (2016).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Torene, R. I. et al. Systematic analysis of variants escaping nonsense-mediated decay uncovers candidate Mendelian diseases. Am. J. Hum. Genet. 111, 70\u201381 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Potter, A. S. et al. Rare variant in MRC2 associated with familial supraventricular tachycardia and Wolff-Parkinson-White syndrome. Circ. Genomic Precis. Med. 17, e004614 (2024).<\/p>\n

    CAS\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gudmundsson, S. et al. Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.06.12.593113 (2024).<\/p>\n<\/li>\n

  • \n

    Rehm, H. L. et al. The landscape of reported VUS in multi-gene panel and genomic testing: time for a change. Genet. Med. 25, 100947 (2023). This multi-laboratory analysis reveals the high prevalence and clinical burden of VUSs in genetic testing from panel testing and advocates for refined reporting practices to reduce VUSs.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dawood, M. et al. Using multiplexed functional data to reduce variant classification inequities in underrepresented populations. Genome Med. 16, 143 (2024). This study defines variant classification disparities in several biobanks and demonstrates how multiplexed functional data can reduce variant classification disparities across ancestries, offering a scalable strategy to make genomic medicine more equitable.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Young, J. L. et al. Beyond race: recruitment of diverse participants in clinical genomics research for rare disease. Front. Genet. 13, 949422 (2022).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wojcik, M. H. et al. Rare diseases, common barriers: disparities in pediatric clinical genetics outcomes. Pediatr. Res. 93, 110\u2013117 (2023).<\/p>\n

    PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Serrano, J. G. et al. Advancing understanding of inequities in rare disease genomics. Clin. Ther. 45, 745\u2013753 (2023).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    D\u2019Angelo, C. S. et al. Barriers and considerations for diagnosing rare diseases in indigenous populations. Front. Pediatr. 8, 579924 (2020).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Savage, S. K. et al. Using a chat-based informed consent tool in large-scale genomic research. J. Am. Med. Inform. Assoc. 31, 472\u2013478 (2024). A chat-based consent tool successfully scaled participant enrollment for large rare disease genomics studies, reducing staff burden while maintaining participant understanding.<\/p>\n

    PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Abou Tayoun, A. N. & Rehm, H. L. Genetic variation in the Middle East\u2014an opportunity to advance the human genetics field. Genome Med. 12, 116 (2020).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    AlAbdi, L. et al. Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families. Nat. Commun. 14, 5269 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    AlAbdi, L. et al. Beyond the exome: utility of long-read whole genome sequencing in exome-negative autosomal recessive diseases. Genome Med. 15, 114 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    AlAbdi, L. et al. Arab founder variants: Contributions to clinical genomics and precision medicine. Med 6, 100528 (2025).<\/p>\n<\/li>\n

  • \n

    Sulem, P. et al. Identification of a large set of rare complete human knockouts. Nat. Genet. 47, 448\u2013452 (2015).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Oddsson, A. et al. Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality. Nat. Commun. 14, 3453 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wenger, T. L. et al. SeqFirst: building equity access to a precise genetic diagnosis in critically ill newborns. Am. J. Hum. Genet. 112, 508\u2013522 (2025).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Stark, Z. et al. A call to action to scale up research and clinical genomic data sharing. Nat. Rev. Genet. 26, 141\u2013147 (2025).<\/p>\n<\/li>\n

  • \n

    Rehm, H. L. Time to make rare disease diagnosis accessible to all. Nat. Med. 28, 241\u2013242 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wilkinson, M. D. et al. The FAIR guiding principles for scientific data management and stewardship. Sci. Data 3, 160018 (2016).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bamshad, M. J., Nickerson, D. A. & Chong, J. X. Mendelian gene discovery: fast and furious with no end in sight. Am. J. Hum. Genet. 105, 448\u2013455 (2019).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wagner, A. H. et al. The GA4GH variation representation specification: a computational framework for variation representation and federated identification. Cell Genom. 1, 100027 (2021).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Pawliczek, P. et al. ClinGen allele registry links information about genetic variants. Hum. Mutat. 39, 1690\u20131701 (2018).<\/p>\n

    PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    K\u00f6hler, S. et al. The Human Phenotype Ontology in 2021. Nucleic Acids Res. 49, D1207\u2013D1217 (2021).<\/p>\n

    PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Stegmann, J. D. et al. Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies. npj Genom. Med. 9, 18 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Herman, I. et al. Quantitative dissection of multilocus pathogenic variation in an Egyptian infant with severe neurodevelopmental disorder resulting from multiple molecular diagnoses. Am. J. Med. Genet. A 188, 735\u2013750 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Calame, D. G. et al. Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease. Am. J. Hum. Genet. 110, 1394\u20131413 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Jolly, A. et al. Rare variant enrichment analysis supports GREB1L as a contributory driver gene in the etiology of Mayer-Rokitansky-K\u00fcster-Hauser syndrome. HGG Adv. 4, 100188 (2023).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lima, A. R. et al. Phenotypic and mutational spectrum of ROR2-related Robinow syndrome. Hum. Mutat. 43, 900\u2013918 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhang, C. et al. Novel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome: WNT signaling perturbation and phenotypic variability. HGG Adv. 3, 100074 (2022).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Garcia, B. T. et al. Improving automated deep phenotyping through large language models using retrieval-augmented generation. Genome Med. 17, 91 (2025).<\/p>\n<\/li>\n

  • \n

    Gustafson, J. A. et al. High-coverage nanopore sequencing of samples from the 1000 Genomes Project to build a comprehensive catalog of human genetic variation. Genome Res. 34, 2061\u20132073 (2024). High-coverage long-read ONT sequencing of 1000 Genomes Project samples enables improved detection of structural variants and epigenetic changes.<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Harrison, P. W. et al. Ensembl 2024. Nucleic Acids Res. 52, D891\u2013D899 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Liu, X., Li, C., Mou, C., Dong, Y. & Tu, Y. dbNSFP v4: a comprehensive database of transcript-specific functional predictions and annotations for human nonsynonymous and splice-site SNVs. Genome Med. 12, 103 (2020).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Pagel, K. A. et al. Integrated informatics analysis of cancer-related variants. JCO Clin. Cancer Inform. 4, 310\u2013317 (2020).<\/p>\n

    PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rodrigues, E. D. S. et al. Variant-level matching for diagnosis and discovery: challenges and opportunities. Hum. Mutat. 43, 782\u2013790 (2022).<\/p>\n

    PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Seaby, E. G. et al. A panel-agnostic strategy \u2018HiPPo\u2019 improves diagnostic efficiency in the UK Genomic Medicine Service. Healthcare 11, 3179 (2023).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chong, J. X. et al. Considerations for reporting variants in novel candidate genes identified during clinical genomic testing. Genet. Med. 26, 101199 (2024).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rai, A. et al. Genomic rare variant mechanisms for congenital cardiac laterality defect: a digenic model approach. Am. J. Hum. Genet. 112, 1664\u20131680 (2025).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    T\u00f6pf, A. et al. Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy. Nat. Genet. 56, 395\u2013407 (2024).<\/p>\n

    PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gifford, C. A. et al. Oligogenic inheritance of a human heart disease involving a genetic modifier. Science 364, 865\u2013870 (2019).<\/p>\n

    CAS\u00a0
    \n PubMed\u00a0
    \n PubMed Central\u00a0<\/p>\n

    Google Scholar\u00a0\n <\/p>\n<\/li>\n

  • \n

    Arriaga, T. M. et al. Transcriptome-wide outlier approach identifies individuals with minor spliceopathies. Am. J. Hum. Genet. 112, 2458\u20132475 (2025).<\/p>\n<\/li>\n","protected":false},"excerpt":{"rendered":"

    Baxter, S. M. et al. Centers for Mendelian Genomics: a decade of facilitating gene discovery. Genet. Med. 24, 784\u2013797 (2022). CAS\u00a0 PubMed\u00a0 PubMed Central\u00a0 Google Scholar\u00a0 Taylor, J. C. et al. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders. Nat. Genet. 47, 717\u2013726 (2015). CAS\u00a0 PubMed\u00a0 PubMed Central\u00a0 Google Scholar\u00a0<\/p>\n","protected":false},"author":1,"featured_media":33150,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[58],"tags":[16782,737,19021,19020,485],"class_list":{"0":"post-33149","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-science","8":"tag-accelerating","9":"tag-diseases","10":"tag-genomics","11":"tag-gregor","12":"tag-rare"},"_links":{"self":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts\/33149","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=33149"}],"version-history":[{"count":0,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts\/33149\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/media\/33150"}],"wp:attachment":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=33149"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=33149"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=33149"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}