Application of high-resolution array platform for genome-wide copy number variation analysis in patients with nonsyndromic cleft lip and palate
| Autor: | Raul Hernandes Bortolin, André Ducati Luchessi, Karla Simone Costa de Souza, Adriana Augusto de Rezende, Erlane Marques Ribeiro, Maria Edinilma Felinto Brito, Heglayne Pereira Vital da Silva, Marcela Abbott Galvão Ururahy, Valéria Morgiana Gualberto Duarte Moreira Lima, Gustavo Henrique de Medeiros Oliveira, Vera Lúcia Gil-da-Silva-Lopes, Gisele Correia Pacheco Leite, Vivian Nogueira Silbiger, João Felipe Bezerra |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Genetics congenital hereditary and neonatal diseases and abnormalities Candidate gene PHF8 Biochemistry (medical) Clinical Biochemistry Public Health Environmental and Occupational Health Hematology Biology Genome 03 medical and health sciences Medical Laboratory Technology 030104 developmental biology Gene mapping Genetic linkage Immunology and Allergy Copy-number variation Gene Research Articles Comparative genomic hybridization |
| Zdroj: | Journal of Clinical Laboratory Analysis. 32:e22428 |
| ISSN: | 0887-8013 |
| DOI: | 10.1002/jcla.22428 |
| Popis: | Background Although more than 14 loci may be involved in the development of nonsyndromic cleft lip and palate (NSCLP), the etiology has not been fully elucidated due to genetic and environmental risk factor interactions. Despite advances in identifying genes associated with the NSCLP development using traditional genetic mapping strategies of candidate genes, genome-wide studies, and epidemiologic and linkage analysis, microarray techniques have become important complementary tools in the search for potential causative oral clefts genes in genetic studies. Microarray hybridization enables scanning of the whole genome and detecting copy number variants (CNVs). Although common benign CNVs are often smaller, with sizes smaller than 20 kb, here we reveal small exonic CNVs based on the importance of the encompassed genes in cleft lip and palate phenotype. Methods Microarray hybridization analysis was performed in 15 individuals with NSCLP. Results We identified 11 exonic CNVs affecting at least one exon of the candidate genes. Thirteen candidate genes (COL11A1-1p21; IRF6-1q32.3; MSX1-4p16.2; TERT-5p15.33; MIR4457-5p15.33; CLPTM1L-5p15.33; ESR1-6q25.1; GLI3-7p13; FGFR-8p11.23; TBX1-22q11.21; OFD-Xp22; PHF8-Xp11.22; and FLNA-Xq28) overlapped with the CNVs identified. Conclusions Considering the importance to NSCLP, the microdeletions that encompass MSX1, microduplications over TERT, MIR4457, CLPTM1L, and microduplication of PHF8 have been identified as small CNVs related to sequence variants associated with oral clefts susceptibility. Our findings represent a preliminary study on the clinical significance of small CNVs and their relationship with genes implicated in NSCLP. |
| Databáze: | OpenAIRE |
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