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Background: Mitochondrial ribosomal protein L19 (MRPL19) is a member of the mitochondrial ribosomal protein (MRP) family. MRPs have a role in the progression of many cancers. However, the role of MRPL19 in lung adenocarcinoma (LUAD) is yet unknown. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, real-time polymerase chain reaction, and immunohistochemistry (IHC) were used to assess MRPL19 expression and clinical relevance. Gene Expression Profiling Interactive Analysis (GEPIA) and the online Kaplan-Meier (KM) Plotter database were used to determine the prognostic significance. Through use of LinkedOmics, genes that were coexpressed with MRPL19 and its regulators were identified. The biological roles of MRPL19 were investigated through R-implemented packages and RNA interference. The Tumor Immune Estimation Resource (TIMER) was employed to assess the connection between MRPL19 expression and infiltrated immune cells in LUAD. Results: MRPL19 expression in LUAD was upregulated and was correlated with lymph node metastasis, differentiation level, and tumor status. MRPL19 was prognostic and associated with poor prognosis. Functional network analysis revealed that MRPL19 may be associated with the cell cycle, cell adhesion molecules, spliceosome, and T-helper cell differentiation and was regulated by several microRNA and the E2F family. The gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network indicated that MRPL19 was correlated with cancer proliferation signaling pathways. The immune infiltration analysis revealed a correlation between MRPL19 expression and the extent of B cells, CD4+ T cells, and dendritic cells' infiltration in LUAD. Additionally, MRPL19 knockdown in LUAD cells substantially reduced cell growth, migration, and invasion of malignant cells. Conclusions: The poor prognosis and immunological infiltration in LUAD were significantly associated with MRPL19, which may have pro-oncogenic effects on the disease.

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Mitochondrial ribosomal proteins (MRPs) are essential components for the structural and functional integrity of the mitoribosome complex. Throughout evolution, the mammalian mitoribosome has acquired new Mrp genes to compensate for loss of ribosomal RNA. More than 80 MRPs have been identified in mammals. Here we document expression pattern of 79 Mrp genes during mouse development and adult tissues and find that these genes are consistently expressed throughout early embryogenesis with little stage or tissue specificity. Further investigation of the amino acid sequence reveals that this group of proteins has little to no protein similarity. Recent work has shown that the majority of Mrp genes are essential resulting in early embryonic lethality, suggesting no functional redundancy among the group. Taken together, these results indicate that the Mrp genes are not a gene family descended from a single ancestral gene, and that each MRP has unique and essential role in the mitoribosome complex. The lack of functional redundancy is surprising given the importance of the mitoribosome for cellular and organismal viability. Further, these data suggest that genomic variants in Mrp genes may be causative for early pregnancy loss and should be evaluated as clinically.

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Language and communication development is a complex process influenced by numerous environmental and genetic factors. Many neurodevelopment disorders include deficits in language and communication skills in their diagnostic criteria, including autism spectrum disorders (ASD), language impairment (LI), and dyslexia. These disorders are polygenic and complex with a significant genetic component contributing to each. The similarity of language phenotypes and comorbidity of these disorders suggest that they may share genetic contributors. To test this, we examined the association of genes previously implicated in dyslexia, LI, and/or language-related traits with language skills in children with ASD. We used genetic and language data collected in the Autism Genome Research Exchange (AGRE) and Simons Simplex Collection (SSC) cohorts to perform a meta-analysis on performance on a receptive vocabulary task. There were associations with LI risk gene ATP2C2 and dyslexia risk gene MRPL19. Additionally, we found suggestive evidence of association with CMIP, GCFC2, KIAA0319L, the DYX2 locus (ACOT13, GPLD1, and FAM65B), and DRD2. Our results show that LI and dyslexia genes also contribute to language traits in children with ASD. These associations add to the growing literature of generalist genes that contribute to multiple related neurobehavioral traits. Future studies should examine whether other genetic contributors may be shared among these disorders and how risk variants interact with each other and the environment to modify clinical presentations.

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Chromosomal microarray analysis is now commonly used in clinical practice to identify copy number variants (CNVs) in the human genome. We report our experience with the use of the 105 K and 180K oligonucleotide microarrays in 215 consecutive patients referred with either autism or autism spectrum disorders (ASD) or developmental delay/learning disability for genetic services at the University of Kansas Medical Center during the past 4 years (2009-2012). Of the 215 patients [140 males and 75 females (male/female ratio=1.87); 65 with ASD and 150 with learning disability], abnormal microarray results were seen in 45 individuals (21%) with a total of 49 CNVs. Of these findings, 32 represented a known diagnostic CNV contributing to the clinical presentation and 17 represented non-diagnostic CNVs (variants of unknown significance). Thirteen patients with ASD had a total of 14 CNVs, 6 CNVs recognized as diagnostic and 8 as non-diagnostic. The most common chromosome involved in the ASD group was chromosome 15. For those with a learning disability, 32 patients had a total of 35 CNVs. Twenty-six of the 35 CNVs were classified as a known diagnostic CNV, usually a deletion (n=20). Nine CNVs were classified as an unknown non-diagnostic CNV, usually a duplication (n=8). For the learning disability subgroup, chromosomes 2 and 22 were most involved. Thirteen out of 65 patients (20%) with ASD had a CNV compared with 32 out of 150 patients (21%) with a learning disability. The frequency of chromosomal microarray abnormalities compared by subject group or gender was not statistically different. A higher percentage of individuals with a learning disability had clinical findings of seizures, dysmorphic features and microcephaly, but not statistically significant. While both groups contained more males than females, a significantly higher percentage of males were present in the ASD group.

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