A study on the correlation between IL1RAPL1 and human cognitive ability

Gao, Xiaocai; Xi, Guan; Niu, Yin-bo; Zhang, Shumiao; Fu, Ruijuan; Zheng, Zijian; Zhang, Kejin; Lv, Shumin; He, Hui; Xue, Min; Zhang, Fuchang

doi:10.1016/j.neulet.2008.03.084

Cited by 16 publications

(12 citation statements)

References 20 publications

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“…At Xp21.3 (41–47), we find a partial duplication of the gene encoding interleukin 1 receptor accessory protein-like 1, IL1RAPL1 (OR=1.6, 95% CI, 0.3–7.7). While sex-specific effects of CNVs on chromosome X is the expectation, it is curious that females rather than males with the IL1RAPL1 duplication appear to be at higher risk (Table 1).…”

Section: Resultsmentioning

confidence: 92%

“…A loss of function results in a truncated protein that is unable to control neurite out-growth in hippocampal neurons (41). Males with deletions and mutations of IL1RAPL1 exhibit a range of neurological disorders such as X-linked mental retardation (MR), autism, and cognitive impairments (OMIM #300206; #300143) (41–47) whereas females are not necessarily affected. Duplicated genes on chromosome X often show sexually dimorphic expression due to skewed X inactivation; in females, a duplicated or disrupted gene is often silenced by the X inactivation mechanism.…”

Section: Discussionmentioning

confidence: 99%

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Copy Number Variants for Schizophrenia and Related Psychotic Disorders in Oceanic Palau: Risk and Transmission in Extended Pedigrees

Melhem

Middleton

McFadden

et al. 2011

Biological Psychiatry

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Background We report on copy number variants (CNVs) found in Palauan subjects ascertained for schizophrenia and related psychotic disorders in extended pedigrees in Palau. We compare CNVs found in this Oceanic population to those seen in other samples, typically of European ancestry. Assessing CNVs in Palauan extended pedigrees yields insight into the evolution of risk CNVs, such as how they arise, are transmitted, and are lost from populations by stochastic or selective processes, none of which is easily measured from case-control samples. Methods DNA samples from 197 subjects affected with schizophrenia and related psychotic disorders, 185 of their relatives, and 159 controls were successfully characterized for CNVs using Affymetrix Genomewide Human SNP Array 5.0. Results CNVs thought to be associated with risk for schizophrenia and related disorders also occur in affected individuals in Palau, specifically 15q11.2 and 1q21.1 deletions, partial duplication of IL1RAPL1 (Xp21.3), and chromosome X duplications (Klinefleter’s syndrome). Partial duplication within A2BP1 appears to convey an 8-fold increased risk in males (95% CI, 0.8–84.4) but not females (OR=0.4, 95% CI, 0.03–4.9). Affected-only linkage analysis using this variant yields a LOD score of 3.5. Conclusions This study reveals CNVs that confer risk to schizophrenia and related psychotic disorders in Palau, most of which have been previously observed in samples of European ancestry. Only a few of these CNVs show evidence that they have existed for many generations, consistent with risk variants diminishing reproductive success.

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Section: Resultsmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Copy Number Variants for Schizophrenia and Related Psychotic Disorders in Oceanic Palau: Risk and Transmission in Extended Pedigrees

Melhem

Middleton

McFadden

et al. 2011

Biological Psychiatry

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“…The C-terminal tail could of course mediate a function entirely independent of IL-1 signaling. In the case of the X-linked receptor family member APL, which is genetically associated with cognitive function and autism in humans, the C-terminal extension is reported to interact with neuronal calcium sensor-1 and regulate neuron growth (Bhat et al, 2008; Gambino et al, 2007; Gao et al, 2008; Piton et al, 2008; Tabolacci et al, 2006). The C-terminal extension of AcPb also offers the opportunity to interact with other proteins, recruiting them to the receptor complex or perhaps affecting the cellular location of the complex.…”

Section: Discussionmentioning

confidence: 99%

A Central Nervous System-Restricted Isoform of the Interleukin-1 Receptor Accessory Protein Modulates Neuronal Responses to Interleukin-1

et al. 2009

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SUMMARY IL-1 has multiple functions in both the periphery and the central nervous system (CNS) and is regulated at many levels. We identified a novel isoform of the IL-1R Accessory Protein (termed AcPb) that is expressed exclusively in the CNS. AcPb interacted with IL-1 and the IL-1 receptor but was unable to mediate canonical IL-1 responses. AcPb expression, however, modulated neuronal gene expression in response to IL-1 treatment in vitro. Animals lacking AcPb demonstrated an intact peripheral IL-1 response and developed experimental autoimmune encephalomyelitis (EAE) similarly to wild type mice. AcPb-deficient mice were instead more vulnerable to local inflammatory challenge in the CNS and suffered enhanced neuronal degeneration as compared to AcP-deficient or wild type mice. These findings implicate AcPb as an additional component of the highly regulated IL-1 system and suggest it may play a role in modulating CNS responses to IL-1 and the interplay between inflammation and neuronal survival.

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“…Like NCS-1, IL1RAPL1 has been implicated in nervous system development [27], and in particular in neurite outgrowth and differentiation [26], [28]. The gene encoding IL1RAPL1 is on the X chromosome, and has been found to be mutated in a number of cases of X-linked mental retardation [25], [29], [30], [31], [32], and polymorphisms in the gene have been associated with differences in human cognition [33]. In a recent study, linkage analysis has suggested an association between loss of function mutations in the gene encoding IL1RAPL1 and a number of cases of familial autism and autistic spectrum disorder (ASD) [34].…”

Section: Introductionmentioning

confidence: 99%

Structural and Functional Deficits in a Neuronal Calcium Sensor-1 Mutant Identified in a Case of Autistic Spectrum Disorder

et al. 2010

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Neuronal calcium sensor-1 (NCS-1) is a Ca2+ sensor protein that has been implicated in the regulation of various aspects of neuronal development and neurotransmission. It exerts its effects through interactions with a range of target proteins one of which is interleukin receptor accessory protein like-1 (IL1RAPL1) protein. Mutations in IL1RAPL1 have recently been associated with autism spectrum disorders and a missense mutation (R102Q) on NCS-1 has been found in one individual with autism. We have examined the effect of this mutation on the structure and function of NCS-1. From use of NMR spectroscopy, it appeared that the R102Q affected the structure of the protein particularly with an increase in the extent of conformational exchange in the C-terminus of the protein. Despite this change NCS-1(R102Q) did not show changes in its affinity for Ca2+ or binding to IL1RAPL1 and its intracellular localisation was unaffected. Assessment of NCS-1 dynamics indicated that it could rapidly cycle between cytosolic and membrane pools and that the cycling onto the plasma membrane was specifically changed in NCS-1(R102Q) with the loss of a Ca2+ -dependent component. From these data we speculate that impairment of the normal cycling of NCS-1 by the R102Q mutation could have subtle effects on neuronal signalling and physiology in the developing and adult brain.

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A study on the correlation between IL1RAPL1 and human cognitive ability

Cited by 16 publications

References 20 publications

Copy Number Variants for Schizophrenia and Related Psychotic Disorders in Oceanic Palau: Risk and Transmission in Extended Pedigrees

Copy Number Variants for Schizophrenia and Related Psychotic Disorders in Oceanic Palau: Risk and Transmission in Extended Pedigrees

A Central Nervous System-Restricted Isoform of the Interleukin-1 Receptor Accessory Protein Modulates Neuronal Responses to Interleukin-1

Structural and Functional Deficits in a Neuronal Calcium Sensor-1 Mutant Identified in a Case of Autistic Spectrum Disorder

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