Confirmation of the association of the C4B null allelle in autism

Odell, Dennis; Maciulis, Alma; Cutler, Adele; Warren, Louise; McMahon, William M.; Coon, Hilary; Stubbs, G. Maxwell; K, Henley; Torres, Anthony R.

doi:10.1016/j.humimm.2004.11.002

Cited by 112 publications

(93 citation statements)

References 48 publications

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“…6,36,37 The exact relationship between disorder and RCCX is unambiguous when a defective gene is involved; 7,38 most often, however, identification of the real causative factors proves fairly challenging. RCCX disease association studies have mainly focused on C4 GCNs, [39][40][41] but forgetting about the complexity of RCCX variations and the longrange LD characteristics of the MHC hides the danger of overseeing the genuine molecular background. More and more detailed descriptions of the region are thus indispensable for our better understanding of RCCX-related disease associations, the first step on the road leading to the most effective prevention and treatments possible.…”

Section: Characterization Of Rccx Variants Z Bánlaki Et Almentioning

confidence: 99%

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

et al. 2012

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The human RCCX is a common multiallelic copy number variation locus whose number of segments varies between one and four in a chromosome. The monomodular form normally comprises four functional genes, but in duplicated RCCX segments generally only the gene-encoding complement component C4 produces a protein. C4 genes can code either for a C4A or a C4B isotype protein and exhibit dichotomous size variation. Distinct RCCX variants show association with numerous diseases; however, identification of the basis of these associations is often challenging, not least because the RCCX is localized in the major histocompatibility complex (MHC) region, a genomic area characterized by exceedingly long-range linkage disequilibrium. Here we present a detailed analysis on RCCX variants and their relationship with so-called 'ancestral' or 'conserved extended' MHC haplotypes in healthy Caucasians. In addition to former investigations, precise order and size of all C4A and C4B genes were determined even in trimodular RCCX structures. Considering C4 copy numbers, length, isotype specificity and CYP21A2 copy numbers, we have identified 15 distinct RCCX variants and described the RCCX structures involved in 29 repeatedly occurring MHC haplotypes. The findings should become a useful tool for future RCCX-and MHC-related disease association studies.

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Section: Characterization Of Rccx Variants Z Bánlaki Et Almentioning

confidence: 99%

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

et al. 2012

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“…More than half of the C4B null alleles in subjects with autism involved C4A duplications. 14 It is possible that a modest genetic abnormality of C4B might affect other complement proteins including fibronectin, C1q and FHR-1.…”

Section: Complement Protein C1q and The Classical Pathwaymentioning

confidence: 99%

“…[8][9][10] Although previous linkage studies have identified a number of potential genetic loci for autism, only a few of these regions have been confirmed. [11][12][13][14][15][16][17] No single gene or group of genes have been unequivocally linked to autism, leading to suggestions that as many as 15 genes may weakly interact to confer a susceptibility to the disorder. 18,19 Among the genes implicated in autism, several relate to immune regulation and function, including HLA-antigen presentation molecules and components of the complement system.…”

Section: Introductionmentioning

confidence: 99%

“…18,19 Among the genes implicated in autism, several relate to immune regulation and function, including HLA-antigen presentation molecules and components of the complement system. 14,[20][21][22][23][24][25][26][27] Although abnormalities of cytokines and chemokines have been reported in the blood of patients with autism including plasma levels of tumor necrosis factor-a (TNF)-a, TNF receptor II, Interferon-gamma (IFNg), Interleukin-12 (IL-12), and IL-10, no definitive profile has emerged. Indeed, the changes reported in cytokine levels may occur in separate subgroups of autism subjects that have different clinical phenotypes.…”

Section: Introductionmentioning

confidence: 99%

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A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Corbett

Kantor²,

Schulman³

et al. 2006

Mol Psychiatry

167

113

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Modern methods that use systematic, quantitative and unbiased approaches are making it possible to discover proteins altered by a disease. To identify proteins that might be differentially expressed in autism, serum proteins from blood were subjected to trypsin digestion followed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) on time-of-flight (TOF) instruments to identify differentially expressed peptides. Children with autism 4-6 years of age (n = 69) were compared to typically developing children (n = 35) with similar age and gender distributions. A total of 6348 peptide components were quantified. Of these, five peptide components corresponding to four known proteins had an effect size > 0.99 with a P < 0.05 and a Mascot identification score of 30 or greater for autism compared to controls. The four proteins were: Apolipoprotein (apo) B-100, Complement Factor H Related Protein (FHR1), Complement C1q and Fibronectin 1 (FN1). In addition, apo B-100 and apo A-IV were higher in children with high compared to low functioning autism. Apos are involved in the transport of lipids, cholesterol and vitamin E. The complement system is involved in the lysis and removal of infectious organisms in blood, and may be involved in cellular apoptosis in brain. Despite limitations of the study, including the low fold changes and variable detection rates for the peptide components, the data support possible differences of circulating proteins in autism, and should help stimulate the continued search for causes and treatments of autism by examining peripheral blood.

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“…It was reported that a C4B null allele (C4B gene deletion) was significantly more common in subjects with autism than in subjects without autism. This initial finding was supported by additional research in our laboratory that showed a relative risk of 4 for subjects with autism who have a C4B null allele (Odell et al, 2005). Interestingly, Mostafa & Shehab (2010) supported this observation with an odds ratio of 6 for autism subjects with a C4B null allele and an odds ratio 6.26 for children with autism and a family history of autoimmune diseases in an Egyptian population.…”

Section: Immune System Abnormalities In Autism 81 Humoral Innate Systemmentioning

confidence: 66%

Immune Dysfunction in Autism Spectrum Disorder

Westover¹,

Sweeten²,

Benson³

et al. 2011

Autism - A Neurodevelopmental Journey From Genes to Behaviour

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Confirmation of the association of the C4B null allelle in autism

Cited by 112 publications

References 48 publications

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Immune Dysfunction in Autism Spectrum Disorder

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