Novel mutations in genes causing hereditary spastic paraplegia and Charcot-Marie-Tooth neuropathy identified by an optimized protocol for homozygosity mapping based on whole-exome sequencing

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dc.contributor.authorKancheva, Daliya
dc.contributor.authorAtkinson, Derek
dc.contributor.authorDe Rijk, Peter
dc.contributor.authorZimon, Magdalena
dc.contributor.authorChamova, Teodora
dc.contributor.authorMitev, Vanyo
dc.contributor.authorYaramis, Ahmet
dc.date.accessioned2024-04-24T16:19:12Z
dc.date.available2024-04-24T16:19:12Z
dc.date.issued2016
dc.departmentDicle Üniversitesien_US
dc.description.abstractPurpose: Homozygosity mapping is an effective approach for detecting molecular defects in consanguineous families by delineating stretches of genomic DNA that are identical by descent. Constant developments in next-generation sequencing created possibilities to combine whole-exome sequencing (WES) and homozygosity Mapping in a single step. Methods: Basic optimization of homozygosity mapping parameters was performed in a group of families with autosomal-recessive (AR) mutations for which both single-nucleotide polymorphism (SNP) array and WES data were available. We varied the criteria for SNP extraction and PLINK thresholds to estimate their effect on the accuracy of homozygosity mapping based on WES. Results: Our protocol showed high specificity and sensitivity for homozygosity detection and facilitated the identification of novel mutations in GAN, GBA2, and ZFYVE26 in four families affected by hereditary spastic paraplegia or Charcot-Marie-Tooth disease. Filtering and mapping with optimized parameters was integrated into the HOMWES (homozygosity mapping based on WES analysis) tool in the GenomeComb package for genomic data analysis. Conclusion: We present recommendations for detection of homozygous regions based on WES data and a bioinformatics tool for their identification, which can be widely applied for studying AR disorders.en_US
dc.description.sponsorshipUniversity of Antwerp [TOP BOF 29069]; Fund for Scientific Research-Flanders; Tom Wahlig Foundation, Jena, Germany; Bogazici University Research Fund [11B01P7]; Boehringer Ingelheim Fonds, Germanyen_US
dc.description.sponsorshipThe authors are grateful to all study participants and their families for their cooperation and thank Luba Kalaydjieva for helpful discussions and Banu Anlar for assisting in patient descriptions. This work was funded in part by the University of Antwerp (TOP BOF 29069 to A.J.); the Fund for Scientific Research-Flanders (to A.J.), Tom Wahlig Foundation, Jena, Germany (to A.J. and I.T.); and the Bogazici University Research Fund (11B01P7 to E.B.). D.A. and A.E.C. are supported by fellowships from the Fund for Scientific Research-Flanders. D.K. received a travel grant from the Boehringer Ingelheim Fonds, Germany.en_US
dc.identifier.doi10.1038/gim.2015.139
dc.identifier.endpage607en_US
dc.identifier.issn1098-3600
dc.identifier.issn1530-0366
dc.identifier.issue6en_US
dc.identifier.pmid26492578
dc.identifier.scopus2-s2.0-84975045805
dc.identifier.scopusqualityQ1
dc.identifier.startpage600en_US
dc.identifier.urihttps://doi.org/10.1038/gim.2015.139
dc.identifier.urihttps://hdl.handle.net/11468/16432
dc.identifier.volume18en_US
dc.identifier.wosWOS:000378184300009
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofGenetics in Medicine
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCharcot-Marie-Tooth Neuropathyen_US
dc.subjectHereditary Spastic Paraplegiaen_US
dc.subjectHomozygosity Mappingen_US
dc.subjectPlinken_US
dc.subjectWhole-Exome Sequencingen_US
dc.titleNovel mutations in genes causing hereditary spastic paraplegia and Charcot-Marie-Tooth neuropathy identified by an optimized protocol for homozygosity mapping based on whole-exome sequencingen_US
dc.titleNovel mutations in genes causing hereditary spastic paraplegia and Charcot-Marie-Tooth neuropathy identified by an optimized protocol for homozygosity mapping based on whole-exome sequencing
dc.typeArticleen_US

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