Application of high-resolution array platform for genome-wide copy number variation analysis in patients with nonsyndromic cleft lip and palate.

Autor:	da Silva HPV; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil., Oliveira GHM; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil., Ururahy MAG; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil., Bezerra JF; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil., de Souza KSC; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil., Bortolin RH; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil., Luchessi AD; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil., Silbiger VN; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil., Lima VMGDM; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil., Leite GCP; Department of Pediatrics, Federal University of Rio Grande do Norte, Natal, Brazil., Brito MEF; Department of Pediatrics, Federal University of Rio Grande do Norte, Natal, Brazil., Ribeiro EM; Medical Genetics Service, Albert Sabin Children's Hospital, Fortaleza, Brazil., Gil-da-Silva-Lopes VL; Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil., de Rezende AA; Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil.
Jazyk:	angličtina
Zdroj:	Journal of clinical laboratory analysis [J Clin Lab Anal] 2018 Jul; Vol. 32 (6), pp. e22428. Date of Electronic Publication: 2018 Mar 07.
DOI:	10.1002/jcla.22428
Abstrakt:	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. (© 2018 Wiley Periodicals, Inc.)
Databáze:	MEDLINE
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