Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA339259 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach [SNP array]
| PRJNA339465 | ENA
Project description:MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach
| PRJNA339466 | ENA
Project description:Orofacial clefts are one of the most common birth defects, affecting 1-2 per 1000 births, and have a complex etiology. High-resolution array-based comparative genomic hybridization has increased the ability to detect copy number variants that can be causative for complex diseases such as cleft lip and/or palate. Utilizing this technique on 97 non-syndromic cleft lip and palate cases and 43 cases with cleft palate only, we identified a heterozygous deletion of Isthmin 1 in one affected case, as well as a deletion in a second case which removes putative 3' regulatory information. Isthmin 1 is a strong candidate for clefting as it is expressed in orofacial structures derived from the first branchial arch and is also in the same synexpression group as fibroblast growth factor 8 and sprouty RTK signaling antagonist 1a and 2, all of which have been associated with clefting. Copy number variants affecting Isthmin 1 are exceedingly rare in control populations, and Isthmin 1 scores as a likely haploinsufficiency locus. Confirming its role in craniofacial development, knockdown or CRISPR/Cas9-generated mutation of isthmin 1 in Xenopus laevis resulted in mild to severe craniofacial dysmorphologies, with several individuals presenting with median clefts. Moreover, knockdown of isthmin 1 produced decreased expression of LIM homeobox 8, itself a gene associated with clefting, in regions of the face that pattern the maxilla. Our study demonstrates a successful pipeline from copy number variant identification of a candidate gene to functional validation in a vertebrate model system and reveals Isthmin 1 as both a new human clefting locus as well as a key craniofacial patterning gene.
2018-01-17 | GSE100845 | GEO
Project description:Genetic Analysis of Syndromic Orofacial Clefting
| PRJNA860701 | ENA
Project description:Genetic Analysis of Syndromic Orofacial Clefting
| PRJNA860702 | ENA
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
2014-05-01 | GSE54089 | GEO
Project description:Genetic analysis of gene expression level is a promising approach for characterizing candidate genes that are involved in complex economic traits such as meat quality. In the present study, we conducted expression quantitative trait loci (eQTL) and allele-specific expression (ASE) analyses based on RNA-sequencing (RNAseq) data from the longissimus muscle of 189 Duroc × Luchuan crossed pigs in order to identify some candidate genes for meat quality traits. Using a genome-wide association study based on a fixed linear model, we identified 7,192 cis-eQTL corresponding to 2,098 cis-genes (p ≤ 1.33e-3, FDR ≤ 0.05) and 6,400 trans-eQTL corresponding to 863 trans-genes (p ≤ 1.13e-6, FDR ≤ 0.05). ASE analysis using RNAseq SNPs identified 9,815 significant ASE-SNPs in 2,253 unique genes. Integrative analysis between the cis-eQTL and ASE target genes identified 540 common genes, including 33 genes with expression levels that were correlated with at least one meat quality trait. Among these 540 common genes, 63 have been reported previously as candidate genes for meat quality traits, such as PHKG1 (q-value = 1.67e-6 for the leading SNP in the cis-eQTL analysis), NUDT7 (q-value = 5.67e-13), FADS2 (q-value = 8.44e-5), and DGAT2 (q-value = 1.24e-3).This study provides valuable information on the genetics of gene expression in porcine skeletal muscle. The characterized cis-genes and ASE genes, combined with the correlations between gene expression level and meat quality traits will be useful to prioritize candidate genes in further studies.
2019-06-24 | GSE124315 | GEO
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven M-bM-^@M-^Xhotspots,M-bM-^@M-^Y seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a M-bM-^@M-^XfertileM-bM-^@M-^Y subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. Gene expression was measured in whole testis in males aged 70(M-BM-15) days. Samples include 294 WSB/EiJ x PWD/PhJ F2s, 11 PWD/PhJ x WSB/EiJ F2s, 8 WSB/EiJ, 8 PWD/PhJ, 6 PWD/PhJ x WSB/EiJ F1s and 4 WSB/EiJ x PWD/PhJ F1s.
2014-05-01 | E-GEOD-54089 | biostudies-arrayexpress
Project description:The cranial neural crest plays a fundamental role in orofacial development and morphogenesis. As a pluripotent and dynamic cell population, the cranial neural crest is undergoing vast transcriptional alterations throughout embryogenesis and the formation of facial structures. These transcriptional changes are regulated by several transcription factors and remodeling complexes. Previously, we revealed the relevance of the Ep400/Kat5 histone acetyltransferase complex in the cranial neural crest and showed that the knockout of Ep400 causes neural crest-related malformations such as orofacial clefting. Furthermore, a case study identified three patients carrying missense mutations in Kat5 who showed severe mental impairments as well as orofacial clefts.2 The exact molecular causes and mechanisms, however, are still unknown. In this study we selectively knocked out Ep400 or Kat5 in the murine cranial neural crest cell line O9-1 to examine its roles in neural crest biology. To understand the regulatory effects of Ep400 and Kat5, knockout neural crest cells were investigated via bulk RNA sequencing to unravel transcriptomic changes in the affected cells. Bioinformatic analyses hinted at the regulation of major cellular functions such as proliferation, ATP generation and protein synthesis by the Ep400/Kat5 complex. Reduced proliferation was confirmed by crystal violet staining, phospho-histone H3 staining and the determination of mitotic cells with condensed chromatin in vitro. We did not detect increased apoptosis in the knockout cell lines. The energetic profile of the cells was investigated by Seahorse technology. The ATP-rate assay showed a decreased glycolytic activity in Ep400- or Kat5-deficient cells. An O-propargyl-puromycin (OPP) Click-iT assay revealed a significant reduction in protein synthesis. To verify in vivo the discovered in vitro effects, Ep400 and Kat5 were selectively ablated in cranial neural crest using Wnt1-Cre in transgenic mice. The knockout of each of the subunits resulted in severe craniofacial malformations from E12.5 onwards. At E10.5 a significant reduction in neural crest-derived tissue and proliferation rate was evident. The strong defect in orofacial structures of mice lacking Kat5 or Ep400 completely correspond to the milder orofacial malformations in patients carrying heterozygous missense mutations. Our results furthermore argue that changes of metabolism, protein synthesis and proliferation in cranial neural crest cells are responsible for the orofacial defects observed in patients.
2023-03-23 | GSE215109 | GEO
Project description:Transcription factor paralogs may share a common role (e.g. Hox) in staged or overlapping expression in specific tissues. In other examples, members have distinct roles in a range of embryologic, differentiation or response pathways (e.g. Tbx, Pax). For the Interferon Regulatory Factor (IRF) family of transcription factors, mice deficient in Irf1, Irf2, Irf3, Irf4, Irf5, Irf7, Irf8 or Irf9, have defects in the immune response but display no embryologic abnormalities. Mice deficient for Irf6 have not been reported, but in humans, mutations in IRF6 cause two Mendelian orofacial clefting syndrome, and genetic variation in IRF6 confers risk for isolated cleft lip and palate. Mice deficient for Irf6 have abnormal skin, limb and craniofacial development. Histological and gene expression analyses indicate that the primary defect is in keratinocyte differentiation and proliferation. This study describes a novel role for an IRF family member in epidermal development. Experiment Overall Design: Skin from E17.5 mice was removed and flash frozen for RNA extraction and hybridization on Affymetrix microarrays.
2007-11-13 | E-GEOD-5800 | biostudies-arrayexpress