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Series GSE85814 Query DataSets for GSE85814
Status Public on Apr 19, 2017
Title MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach [SNP array]
Organism Homo sapiens
Experiment type SNP genotyping by SNP array
Summary A valuable approach to understand how individual and population genetic differences can predispose to disease is to assess the impact of genetic variants on cellular functions (e.g., gene expression) of cell and tissue types related to pathological states. To understand the genetic basis of nonsyndromic cleft lip with or without cleft palate (NSCL/P) susceptibility, a complex and highly prevalent congenital malformation, we searched for genetic variants with a regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle [OOM]), of affected individuals. From 46 OOM samples, which are frequently discarded during routine corrective surgeries on patients with orofacial clefts, we derived mesenchymal stem cells and correlated the individual genetic variants with gene expression from these cultured cells. Through this strategy, we detected significant cis-eQTLs (i.e., DNA variants affecting gene expression) and selected a few candidates to conduct an association study in a large Brazilian cohort (624 patients and 668 controls). This resulted in the discovery of a novel susceptibility locus for NSCL/P, rs1063588, the best eQTL for the MRPL53 gene, where evidence for association was mostly driven by the Native American ancestry component of our Brazilian sample. MRPL53 (2p13.1) encodes a 39S protein subunit of mitochondrial ribosomes and interacts with MYC, a transcription factor required for normal facial morphogenesis. Our study illustrates not only the importance of sampling admixed populations but also the relevance of measuring the functional effects of genetic variants over gene expression to dissect the complexity of disease phenotypes.
 
Overall design In order to understand the genetic basis of NSCL/P susceptibility, we searched for genetic variants with regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle, OOM) of affected individuals. From OOM samples, which are frequently discarded during corrective surgeries that patients with orofacial clefts routinely undergo, we derived mesenchymal stem cells (OOMMSC), and correlated the individual genetic differences with gene expression. We obtained OOM samples from 43 NSCL/P-affected and four normal individuals, and established OOMMSC primary cultures according to previously published protocol. DNA samples extracted from OOMMSC cell cultures were genotyped with the GeneChip Human Mapping 250K Nsp/250K Sty Arrays according to the manufactures’ protocol (Affymetrix, USA).
 
Contributor(s) Masotti C, Brito LA, Passos-Bueno MR
Citation(s) 29053389
Submission date Aug 18, 2016
Last update date Nov 16, 2017
Contact name Cibele Masotti
Organization name University of Sao Paulo
Department Genetics and Evolutionary Biology
Lab Human Development Genetics Lab
Street address Rua do Matao, 277.
City Sao Paulo
State/province São Paulo
ZIP/Postal code 05508-090
Country Brazil
 
Platforms (2)
GPL3718 [Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array
GPL3720 [Mapping250K_Sty] Affymetrix Mapping 250K Sty2 SNP Array
Samples (92)
GSM2284834 F1403Nsp, Patient
GSM2284835 F3292Nsp, Patient
GSM2284836 F3324Nsp, Patient
This SubSeries is part of SuperSeries:
GSE85817 MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach
Relations
BioProject PRJNA339465

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE85814_RAW.tar 2.3 Gb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file

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