Academic Journal
Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India
| Title: | Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India |
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| Authors: | Harsh Sheth, Aadhira Nair, Riddhi Bhavsar, Mahesh Kamate, Vykuntaraju K. Gowda, Ashish Bavdekar, S. S. Kadam, Sheela Nampoothiri, Inusha Panigrahi, Anupriya Kaur, Siddharth Shah, Sanjeev N. Mehta, Sujatha Jagadeesan, Indrani Suresh, Seema Kapoor, Shruti Bajaj, Radha Rama Devi, Ashish R. Prajapati, Koumudi Godbole, Harsh Patel, Zulfiqar Luhar, Raju Shah, Anand Iyer, Sunita Bijarnia, Ratna Dua Puri, Mamta Muranjan, Ami A. Shah, Suvarna Magar, Neerja Gupta, Naresh Tayade, Ajit Gandhi, Ajit Sowani, Shrutikaa Kale, Anil Jalan, Dhaval I Solanki, Ashwin Dalal, Shrikant Mane, C. Ratna Prabha, Frenny Sheth, Chaitanya Joshi, Madhvi Joshi, Jayesh Sheth |
| Source: | Hum Genomics Human Genomics, Vol 18, Iss 1, Pp 1-20 (2024) |
| Publisher Information: | Springer Science and Business Media LLC, 2024. |
| Publication Year: | 2024 |
| Subject Terms: | Male, 0301 basic medicine, FOS: Computer and information sciences, DNA Copy Number Variations, Physiology, Epidemiology, Bioinformatics, Epidemiology and Treatment of Chagas Disease, India, Exon, Dried blood spot, smMIP probes, QH426-470, Lysosomal storage disorders, Polymorphism, Single Nucleotide, Gene, Diagnostic yield, Computational biology, 03 medical and health sciences, Human genetics, Lysosomal Storage Disorders, Biochemistry, Genetics and Molecular Biology, Health Sciences, Chitin Metabolism in Insects and Mammals, Genetics, Humans, Disease, Genetic Testing, DNA sequencing, Molecular Biology, Biology, Internal medicine, 0303 health sciences, Fabry disease, Research, High-Throughput Nucleotide Sequencing, Life Sciences, 3. Good health, Lysosomal Storage Diseases, Molecular Probes, FOS: Biological sciences, Medicine, Female, Cost effective, Lysosomal Storage Disorders in Human Health and Disease |
| Description: | Background Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. Results 903 smMIPs were designed to target exon and exon–intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. Conclusion We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm. |
| Document Type: | Article Other literature type |
| Language: | English |
| ISSN: | 1479-7364 |
| DOI: | 10.1186/s40246-024-00613-9 |
| DOI: | 10.60692/cv2wn-mnq25 |
| DOI: | 10.60692/jc6jm-rqj63 |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/38730490 https://doaj.org/article/8292fe789fb04f60a6890327d1f87871 |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (http://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
| Accession Number: | edsair.doi.dedup.....0de56d04e1dad54655aae0e813dbe7df |
| Database: | OpenAIRE |
| ISSN: | 14797364 |
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| DOI: | 10.1186/s40246-024-00613-9 |