Dawood Moez, Heavner Ben, Wheeler Marsha M, Ungar Rachel A, LoTempio Jonathan, Wiel Laurens, Berger Seth, Bernstein Jonathan A, Chong Jessica X, Délot Emmanuèle C, Eichler Evan E, Gibbs Richard A, Lupski James R, Shojaie Ali, Talkowski Michael E, Wagner Alex H, Wei Chia-Lin, Wellington Christopher, Wheeler Matthew T, Carvalho Claudia M B, Gifford Casey A, May Susanne, Miller Danny E, Rehm Heidi L, Sedlazeck Fritz J, Vilain Eric, O'Donnell-Luria Anne, Posey Jennifer E, Chadwick Lisa H, Bamshad Michael J, Montgomery Stephen B
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
ArXiv. 2024 Dec 18:arXiv:2412.14338v1.
Rare diseases are collectively common, affecting approximately one in twenty individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in DNA sequencing, development of new computational and experimental approaches to prioritize genes and genetic variants, and increased global exchange of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis. The Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium was initiated to study thousands of challenging rare disease cases and families and apply, standardize, and evaluate emerging genomics technologies and analytics to accelerate their adoption in clinical practice. Further, all data generated, currently representing ~7500 individuals from ~3000 families, is rapidly made available to researchers worldwide via the Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) to catalyze global efforts to develop approaches for genetic diagnoses in rare diseases (https://gregorconsortium.org/data). The majority of these families have undergone prior clinical genetic testing but remained unsolved, with most being exome-negative. Here, we describe the collaborative research framework, datasets, and discoveries comprising GREGoR that will provide foundational resources and substrates for the future of rare disease genomics.
罕见病总体上很常见，全球约每二十人中就有一人受其影响。近年来，由于DNA测序技术的进步、用于对基因和遗传变异进行优先级排序的新计算和实验方法的开发以及临床和遗传数据全球交流的增加，罕见病诊断取得了快速进展。然而，超过一半疑似患有罕见病的个体缺乏基因诊断结果。为了研究数千例具有挑战性的罕见病病例和家庭，并应用、规范和评估新兴的基因组技术和分析方法，以加速其在临床实践中的应用，开展了阐明罕见病遗传学的基因组学研究（GREGoR）联盟。此外，目前来自约3000个家庭的约7500名个体所产生的所有数据，都通过基因组数据科学分析、可视化和信息学实验室空间（AnVIL）迅速提供给全球的研究人员，以推动全球为开发罕见病基因诊断方法所做的努力（https://gregorconsortium.org/data）。这些家庭中的大多数此前都接受过临床基因检测，但仍未得到确诊，其中大多数外显子检测结果为阴性。在这里，我们描述了构成GREGoR的合作研究框架、数据集和发现，它们将为罕见病基因组学的未来提供基础资源和支撑。
