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Background: To diagnose the full spectrum of hereditary and congenital diseases, genetic laboratories use many different workflows, ranging from karyotyping to exome sequencing. A single generic high-throughput workflow would greatly increase efficiency. We assessed whether genome sequencing (GS) can replace these existing workflows aimed at germline genetic diagnosis for rare disease.
Methods: We performed short-read GS (NovaSeq™6000; 150 bp paired-end reads, 37 × mean coverage) on 1000 cases with 1271 known clinically relevant variants, identified across different workflows, representative of our tertiary diagnostic centers. Variants were categorized into small variants (single nucleotide variants and indels < 50 bp), large variants (copy number variants and short tandem repeats) and other variants (structural variants and aneuploidies). Variant calling format files were queried per variant, from which workflow-specific true positive rates (TPRs) for detection were determined. A TPR of ≥ 98% was considered the threshold for transition to GS. A GS-first scenario was generated for our laboratory, using diagnostic efficacy and predicted false negative as primary outcome measures. As input, we modeled the diagnostic path for all 24,570 individuals referred in 2022, combining the clinical referral, the transition of the underlying workflow(s) to GS, and the variant type(s) to be detected.
Results: Overall, 95% (1206/1271) of variants were detected. Detection rates differed per variant category: small variants in 96% (826/860), large variants in 93% (341/366), and other variants in 87% (39/45). TPRs varied between workflows (79-100%), with 7/10 being replaceable by GS. Models for our laboratory indicate that a GS-first strategy would be feasible for 84.9% of clinical referrals (750/883), translating to 71% of all individuals (17,444/24,570) receiving GS as their primary test. An estimated false negative rate of 0.3% could be expected.
Conclusions: GS can capture clinically relevant germline variants in a 'GS-first strategy' for the majority of clinical indications in a genetics diagnostic lab.
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http://dx.doi.org/10.1186/s13073-024-01301-y | DOI Listing |
Orphanet J Rare Dis
December 2024
Laboratory Medicine Center, Department of Genetic and Genomic Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Background: GTPBP3 catalyzes τm(s) U biosynthesis at the 34th wobble position of mitochondrial tRNAs, the hypomodification of τmU leads to mitochondrial disease. While twenty-three variants of GTPBP3 have been reported worldwide, the genetic landscape in China remains uncertain.
Methods: By using whole-exome sequencing, the candidate individuals carrying GTPBP3 variants were screened and identified.
BMC Genomics
December 2024
School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy Campus, Roseworthy, South Australia, 5371, Australia.
Background: Fat traits in cattle are considered important due to their contribution to beef eating quality and carcass economic value. Discovering the genes controlling fat traits in cattle will enable better selection of these traits, but identifying these genes in individual experiments has proven difficult. Compared to individual experiments, meta-analyses allow greater statistical power for detecting quantitative trait loci and identifying genes that influence single and multiple economically important fat traits.
View Article and Find Full Text PDFBMC Genomics
December 2024
Feed and Forage Development, International Livestock Research Institute, Addis Ababa, Ethiopia.
Background: Lablab is one of the conventionally grown multi-purpose crops that originated in Africa. It is an annual or short-lived perennial forage legume which has versatile uses (as a vegetable and dry seeds, as food or feed, or as green manure) but is yet to receive adequate research attention and hence remains underexploited. To develop new and highly productive lablab varieties, using genomics-assisted selection, the present study aimed to identify quantitative trait loci associated with agronomically important traits in lablab and to assess the stability of these traits across two different agro-ecologies in Ethiopia.
View Article and Find Full Text PDFPlant Methods
December 2024
Department of Molecular Genetics, Dong-A University, Saha-gu Nakdong-Daero 550 beongil 37, Busan, 49315, Republic of Korea.
Background: Genetic markers are crucial for breeding crops with desired agronomic traits, and their development can be expedited using next-generation sequencing (NGS) and bioinformatics tools. Numerous tools have been developed to design molecular markers, enhancing the convenience, accuracy, and efficiency of molecular breeding. However, these tools primarily focus on genetic variants within short user-input sequences, despite the availability of extensive omics data for genomic variants.
View Article and Find Full Text PDFJ Transl Med
December 2024
Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, China.
Background: Diabetic retinopathy (DR) is the most important complication of Type 2 Diabetes (T2D) in eyes. Despite its prevalence, the early detection and management of DR continue to pose considerable challenges. Our research aims to elucidate potent drug targets that could facilitate the identification of DR and propel advancements in its therapeutic strategies.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!