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Open AccessArticle

The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach

1
Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul 90035-903, Brazil
2
Programa de Pós-Graduação em Genética e Biologia Molecular, Departamento de Genética, UFRGS, Porto Alegre, Rio Grande do Sul 91501-970, Brazil
3
Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul 90035-903, Brazil
*
Author to whom correspondence should be addressed.
Genes 2019, 10(11), 839; https://doi.org/10.3390/genes10110839
Received: 28 June 2019 / Revised: 11 September 2019 / Accepted: 16 September 2019 / Published: 24 October 2019
(This article belongs to the Special Issue Neurofibromatosis 1 Genetics)
Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome that results from dominant loss-of-function mutations mainly in the NF1 gene. Large rearrangements are present in 5–10% of affected patients, generally encompass NF1 neighboring genes, and are correlated with a more severe NF1 phenotype. Evident genotype–phenotype correlations and the importance of the co-deleted genes are difficult to establish. In our study we employed an evolutionary approach to provide further insights into the understanding of the fundamental function of genes that are co-deleted in subjects with NF1 microdeletions. Our goal was to access the ortholog and paralog relationship of these genes in primates and verify if purifying or positive selection are acting on these genes. Fourteen genes were analyzed in twelve mammalian species. Of these, four and ten genes showed positive selection and purifying selection, respectively. The protein, RNF135, showed three sites under positive selection at the RING finger domain, which may have been selected to increase efficiency in ubiquitination routes in primates. The phylogenetic analysis suggests distinct evolutionary constraint between the analyzed genes. With these analyses, we hope to help clarify the correlation of the co-deletion of these genes and the more severe phenotype of NF1. View Full-Text
Keywords: genotype–phenotype correlations; microdeletions; neurofibromatosis type 1; phylogenetic analysis genotype–phenotype correlations; microdeletions; neurofibromatosis type 1; phylogenetic analysis
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Brussa Reis, L.; Turchetto-Zolet, A.C.; Fonini, M.; Ashton-Prolla, P.; Rosset, C. The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach. Genes 2019, 10, 839.

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