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Human endogenous retroviruses with transcriptional potential in the brain. Nakamura, A., Okazaki, Y., Sugimoto, J., Oda, T. Only those genes of the KIAA1245 gene subfamily that contain HERV(K) LTRs in their introns are transcriptionally active. The molecular basis for the difference in immune hemolysis activity of the Chido and Rodgers isotypes of human complement component C4. A comparison of the properties of two classes, C4A and C4B, of the human complement component C4. Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes. Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project. The dichotomous size variation of human complement C4 genes is mediated by a novel family of endogenous retroviruses, which also establishes species-specific genomic patterns among Old World primates. Structure and organization of the C4 genes. A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. The novel complement inhibitor human CUB and Sushi multiple domains 1 (CSMD1) protein promotes factor I-mediated degradation of C4b and C3b and inhibits the membrane attack complex assembly. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Confirmation of HLA class II independent type 1 diabetes associations in the major histocompatibility complex including HLA-B and HLA-A. Genome-wide association study identifies five new schizophrenia loci. Schizophrenia Psychiatric Genome-Wide Association Study Consortium. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. International Schizophrenia Consortium et al.
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Common variants conferring risk of schizophrenia. Common variants on chromosome 6p22.1 are associated with schizophrenia. Biological insights from 108 schizophrenia-associated genetic loci. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Dendritic spine pathology in schizophrenia. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia.
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Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. Progressive reduction in cortical thickness as psychosis develops: a multisite longitudinal neuroimaging study of youth at elevated clinical risk. Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.Ĭannon, T. In mice, C4 mediated synapse elimination during postnatal development. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 ( C4) genes. Schizophrenia’s strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms.