دورية أكاديمية
Genomic answers for children: Dynamic analyses of >1000 pediatric rare disease genomes.
| العنوان: | Genomic answers for children: Dynamic analyses of >1000 pediatric rare disease genomes. |
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| المؤلفون: | Cohen ASA; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO; Department of Pathology and Laboratory Medicine, Children's Mercy Kansas City, Kansas City, MO; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO., Farrow EG; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Abdelmoity AT; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Alaimo JT; Department of Pathology and Laboratory Medicine, Children's Mercy Kansas City, Kansas City, MO; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO., Amudhavalli SM; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Anderson JT; Department of Orthopaedic Surgery, Children's Mercy Kansas City, Kansas City, MO., Bansal L; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Bartik L; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Baybayan P; Pacific Biosciences of California, Inc, Menlo Park, CA., Belden B; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Berrios CD; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Biswell RL; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Buczkowicz P; PhenoTips, Toronto, Canada., Buske O; PhenoTips, Toronto, Canada., Chakraborty S; Pacific Biosciences of California, Inc, Menlo Park, CA., Cheung WA; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Coffman KA; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Cooper AM; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Cross LA; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Curran T; Children's Mercy Research Institute, Kansas City, MO., Dang TTT; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Elfrink MM; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Engleman KL; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Fecske ED; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Fieser C; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Fitzgerald K; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Fleming EA; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Gadea RN; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Gannon JL; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Gelineau-Morel RN; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Gibson M; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Goldstein J; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Grundberg E; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Halpin K; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Harvey BS; Department of Orthopaedic Surgery, Children's Mercy Kansas City, Kansas City, MO., Heese BA; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Hein W; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Herd SM; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Hughes SS; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Ilyas M; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Jacobson J; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Jenkins JL; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Jiang S; Bionano Genomics, Inc, San Diego, CA., Johnston JJ; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Keeler K; Department of Orthopaedic Surgery, Children's Mercy Kansas City, Kansas City, MO., Korlach J; Pacific Biosciences of California, Inc, Menlo Park, CA., Kussmann J; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Lambert C; Pacific Biosciences of California, Inc, Menlo Park, CA., Lawson C; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Le Pichon JB; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Leeder JS; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Little VC; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Louiselle DA; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Lypka M; Bionano Genomics, Inc, San Diego, CA., McDonald BD; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Miller N; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Division of Allergy Immunology Pulmonary and Sleep Medicine, Children's Mercy Kansas City, Kansas City, MO., Modrcin A; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Nair A; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Neal SH; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Oermann CM; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Pacicca DM; Department of Orthopaedic Surgery, Children's Mercy Kansas City, Kansas City, MO., Pawar K; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Posey NL; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Price N; Department of Orthopaedic Surgery, Children's Mercy Kansas City, Kansas City, MO., Puckett LMB; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Quezada JF; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Raje N; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Division of Neonatology, Children's Mercy Kansas City, Kansas City, MO., Rowell WJ; Pacific Biosciences of California, Inc, Menlo Park, CA., Rush ET; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO; Department of Internal Medicine, University of Kansas School of Medicine, Kansas City, MO., Sampath V; Division of Neonatology, Children's Mercy Hospital Kansas City, Kansas City, MO., Saunders CJ; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO; Department of Pathology and Laboratory Medicine, Children's Mercy Kansas City, Kansas City, MO; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO., Schwager C; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Schwend RM; Department of Orthopaedic Surgery, Children's Mercy Kansas City, Kansas City, MO., Shaffer E; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Smail C; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Soden S; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Strenk ME; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Sullivan BR; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Sweeney BR; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Tam-Williams JB; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Walter AM; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Welsh H; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Wenger AM; Pacific Biosciences of California, Inc, Menlo Park, CA., Willig LK; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Yan Y; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO., Younger ST; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO., Zhou D; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Zion TN; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, MO; Division of Genetics, Children's Mercy Kansas City, Kansas City, MO., Thiffault I; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO; Department of Pathology and Laboratory Medicine, Children's Mercy Kansas City, Kansas City, MO; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO. Electronic address: ithiffault@cmh.edu., Pastinen T; Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO; UKMC School of Medicine, University of Missouri Kansas City, Kansas City, MO; Children's Mercy Research Institute, Kansas City, MO. Electronic address: tpastinen@cmh.edu. |
| المصدر: | Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2022 Jun; Vol. 24 (6), pp. 1336-1348. Date of Electronic Publication: 2022 Mar 16. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 9815831 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0366 (Electronic) Linking ISSN: 10983600 NLM ISO Abbreviation: Genet Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2022- : [New York] : Elsevier Original Publication: Baltimore, MD : Lippincott, Williams & Wilkins, c1998- |
| مواضيع طبية MeSH: | Genomics* , Rare Diseases*/diagnosis , Rare Diseases*/genetics, Child ; Genome ; High-Throughput Nucleotide Sequencing ; Humans ; Pedigree ; Sequence Analysis, DNA |
| مستخلص: | Purpose: This study aimed to provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids program. Methods: Extensive analyses of 960 families with suspected genetic disorders included short-read exome sequencing and short-read genome sequencing (srGS); PacBio HiFi long-read genome sequencing (HiFi-GS); variant calling for single nucleotide variants (SNV), structural variant (SV), and repeat variants; and machine-learning variant prioritization. Structured phenotypes, prioritized variants, and pedigrees were stored in PhenoTips database, with data sharing through controlled access the database of Genotypes and Phenotypes. Results: Diagnostic rates ranged from 11% in patients with prior negative genetic testing to 34.5% in naive patients. Incorporating SVs from genome sequencing added up to 13% of new diagnoses in previously unsolved cases. HiFi-GS yielded increased discovery rate with >4-fold more rare coding SVs compared with srGS. Variants and genes of unknown significance remain the most common finding (58% of nondiagnostic cases). Conclusion: Computational prioritization is efficient for diagnostic SNVs. Thorough identification of non-SNVs remains challenging and is partly mitigated using HiFi-GS sequencing. Importantly, community research is supported by sharing real-time data to accelerate gene validation and by providing HiFi variant (SNV/SV) resources from >1000 human alleles to facilitate implementation of new sequencing platforms for rare disease diagnoses. Competing Interests: Conflict of Interest P. Baybayan, S. Chakraborty, J. Korlach, C. Lambert, W.J. Rowell, and A.M. Wenger are employees and shareholders of Pacific Biosciences. P. Buczkowicz and O. Buske are employees of PhenoTips. N. Miller became an employee of Bionano Genomics after contribution to the work described in this manuscript. All other authors declare no conflicts of interest. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: AI; Genome sequencing; Long read sequencing; NGS; Rare disease |
| تواريخ الأحداث: | Date Created: 20220320 Date Completed: 20220602 Latest Revision: 20220721 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.gim.2022.02.007 |
| PMID: | 35305867 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-0366 |
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| DOI: | 10.1016/j.gim.2022.02.007 |