{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:03:58Z","timestamp":1792047838438,"version":"4.4.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CSIR-Institute of Genomics and Integrative Biology"},{"name":"CSIR-IGIB","award":["OLP1120"],"award-info":[{"award-number":["OLP1120"]}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"crossref","award":["5\/4-5\/5\/Ad-hoc\/Neuro\/220\/NCD-I (GAP240)"],"award-info":[{"award-number":["5\/4-5\/5\/Ad-hoc\/Neuro\/220\/NCD-I (GAP240)"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Friedreich\u2019s ataxia, an autosomal recessive disorder, is caused by tandem GAA nucleotide repeat expansions in intron 1 of the frataxin gene. The GAA repeats over 66 in number are considered as pathogenic, and commonly occurring pathogenic repeats are within a range of 600\u20131200. Clinically, the spectrum of features is confined mainly to neurological tissues; however, cardiomyopathy and diabetes mellitus have been reported in 60 and 30% of the subjects, respectively. The accurate detection of GAA repeat count is of utmost importance for clinical genetic correlation, and no study so far has attempted an approach that is of high-throughput nature and defines the exact sequence of GAA repeats. Largely, the method for detection of GAA repeats so far is either through the conventional polymerase chain reaction-based screening or Southern blot, which remains the gold standard method. We utilized an approach of long-range targeted amplification of FXN-GAA repeats using Oxford Nanopore Technologies MinION platform for accurate estimation of repeat length. We were able to achieve successful amplification of GAA repeats ranging from \u223c120 to 1100 at \u223c2600\u00d7 mean coverage. The total throughput achievable through our protocol can allow for screening of up to 96 samples per flow cell in less than 24\u2005h. The proposed method is clinically scalable and deployable for day-to-day diagnostics. In this paper, we demonstrate to resolve the genotype\u2013phenotype correlation of Friedreich\u2019s ataxia patients with better accuracy.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad020","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T05:50:53Z","timestamp":1680155453000},"source":"Crossref","is-referenced-by-count":18,"title":["Sequencing through hyperexpanded Friedreich\u2019s ataxia-GAA repeats by nanopore technology: implications in genotype\u2013phenotype correlation"],"prefix":"10.1093","volume":"5","author":[{"given":"Bharathram","family":"Uppili","sequence":"first","affiliation":[{"name":"Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) , Delhi 110007 , India"},{"name":"Academy for Scientific and Innovative Research , Ghaziabad 201002 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Sharma","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) , Delhi 110007 , India"},{"name":"Academy for Scientific and Innovative Research , Ghaziabad 201002 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istaq","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Neurology Department, Neurosciences Centre, All India Institute of Medical Sciences , New Delhi 110029 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Sahni","sequence":"additional","affiliation":[{"name":"Neurology Department, Neurosciences Centre, All India Institute of Medical Sciences , New Delhi 110029 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivekanand","family":"Asokachandran","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) , Delhi 110007 , India"},{"name":"Academy for Scientific and Innovative Research , Ghaziabad 201002 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil B","family":"Nagaraja","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences , Jodhpur, Rajasthan 342001 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achal K","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Neurology Department, Neurosciences Centre, All India Institute of Medical Sciences , New Delhi 110029 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8278-8396","authenticated-orcid":false,"given":"Mohammed","family":"Faruq","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) , Delhi 110007 , India"},{"name":"Academy for Scientific and Innovative Research , Ghaziabad 201002 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"issue":"5254","key":"2023032912474180100_","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1126\/science.271.5254.1423","article-title":"Friedreich\u2019s ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion","volume":"271","author":"Campuzano","year":"1996","journal-title":"Science"},{"issue":"16","key":"2023032912474180100_","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1056\/NEJM199610173351601","article-title":"Clinical and genetic abnormalities in patients with Friedreich\u2019s ataxia","volume":"335","author":"D\u00fcrr","year":"1996","journal-title":"N Engl J Med"},{"issue":"3","key":"2023032912474180100_","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/brain\/104.3.589","article-title":"Friedreich\u2019s ataxia: A clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features","volume":"104","author":"Harding","year":"1981","journal-title":"Brain"},{"issue":"8","key":"2023032912474180100_","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1136\/jnnp.57.8.977","article-title":"Late onset Friedreich\u2019s disease: Clinical features and mapping of mutation to the FRDA locus","volume":"57","author":"De Michele","year":"1994","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"6","key":"2023032912474180100_","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1212\/WNL.49.6.1617","article-title":"Broadened Friedreich\u2019s ataxia phenotype after gene cloning. 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