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Development and Validation of a Mathematical Model to Predict the Complexity of FMR1 Allele Combinations

2020-11-13Journal article Open access
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dc.contributor.authorRodrigues, Bárbara
dc.contributor.authorVale-Fernandes, Emídio
dc.contributor.authorMaia, N
dc.contributor.authorSantos, Flávia
dc.contributor.authorMarques, Isabel
dc.contributor.authorSantos, Rosário
dc.contributor.authorNogueira, António J. A.
dc.contributor.authorJorge, Paula
dc.date.accessioned2021-11-23T15:04:12Z
dc.date.available2021-11-23T15:04:12Z
dc.date.issued2020-11-13
dc.description.abstractThe polymorphic trinucleotide repetitive region in the FMR1 gene 5'UTR contains AGG interspersions, particularly in normal-sized alleles (CGG < 45). In this range repetitive stretches are typically interrupted once or twice, although alleles without or with three or more AGG interspersions can also be observed. AGG interspersions together with the total length of the repetitive region confer stability and hinder expansion to pathogenic ranges: either premutation (55 < CGG < 200) or full mutation (CGG > 200). The AGG interspersions have long been identified as one of the most important features of FMR1 repeat stability, being particularly important to determine expansion risk estimates in female premutation carriers. We sought to compute the combined AGG interspersion numbers and patterns, aiming to define FMR1 repetitive tract complexity combinations. A mathematical model, the first to compute this cumulative effect, was developed and validated using data from 131 young and healthy females. Plotting of their allelic complexity enabled the identification of two statistically distinct groups - equivalent and dissimilar allelic combinations. The outcome, a numerical parameter designated allelic score, depicts the repeat substructure of each allele, measuring the allelic complexity of the FMR1 gene including the AGGs burden, thus allowing new behavioral scrutiny of normal-sized alleles in females.pt_PT
dc.description.sponsorshipThis work was supported by national funds: FCT/MCTES (Fundação para a Ciência e a Tecnologia) – Project Reference SFRH/BD/136398/2018 to BR, UMIB (Unidade Multidisciplinar de Investigação Biomédica) – Reference UIDP/00215/2020 and UIDB/00215/2020, DEFI (Departamento de Ensino, Formação e Investigação) – Reference 2015-DEFI/145/12, and CESAM (Centro de Estudos do Ambiente e do Mar) – Reference UIDP/50017/2020 and UIDB/50017/2020.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRodrigues B, Vale-Fernandes E, Maia N, et al. Development and Validation of a Mathematical Model to Predict the Complexity of FMR1 Allele Combinations. Front Genet. 2020;11:557147. doi:10.3389/fgene.2020.557147pt_PT
dc.identifier.doi10.3389/fgene.2020.557147pt_PT
dc.identifier.issn1664-8021
dc.identifier.urihttp://hdl.handle.net/10400.16/2627
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontiers Research Foundationpt_PT
dc.relation.publisherversionhttps://www.frontiersin.org/articles/10.3389/fgene.2020.557147/fullpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAGG interspersion patternpt_PT
dc.subjectCGG repeatspt_PT
dc.subjectFMR1 genept_PT
dc.subjectallelic scorept_PT
dc.subjectmodeling allelic complexitypt_PT
dc.titleDevelopment and Validation of a Mathematical Model to Predict the Complexity of FMR1 Allele Combinationspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceSwitzerlandpt_PT
oaire.citation.startPage557147pt_PT
oaire.citation.titleFrontiers in Geneticspt_PT
oaire.citation.volume11pt_PT
person.familyNameRodrigues
person.familyNameVale-Fernandes
person.familyNameMaia
person.familyNameSantos
person.familyNameJorge
person.givenNameBárbara Luísa Cerqueira
person.givenNameEmídio
person.givenNameNuno
person.givenNameRosário
person.givenNamePaula
person.identifier1058137
person.identifier.ciencia-idA61B-D2D1-EE05
person.identifier.ciencia-id7017-129C-1B89
person.identifier.ciencia-id4816-1492-FEB1
person.identifier.ciencia-id5717-2E67-9171
person.identifier.ciencia-idFD15-9412-CF3F
person.identifier.orcid0000-0003-4698-962X
person.identifier.orcid0000-0002-2967-2666
person.identifier.orcid0000-0003-3274-2474
person.identifier.orcid0000-0002-8594-6377
person.identifier.orcid0000-0002-6507-222X
person.identifier.scopus-author-id56578503200
person.identifier.scopus-author-id57193114189
person.identifier.scopus-author-id7201375082
person.identifier.scopus-author-id7005566496
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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