Analysis of the RELN gene as a genetic risk factor for autism. Mol Psychiat

Department of Medicine, Center for Human Genetics, IGSP, Duke University Medical Center, Durham, NC, USA.
Molecular Psychiatry (Impact Factor: 14.5). 07/2005; 10(6):563-71. DOI: 10.1038/
Source: PubMed


Several genome-wide screens have indicated the presence of an autism susceptibility locus within the distal long arm of chromosome 7 (7q). Mapping at 7q22 within this region is the candidate gene reelin (RELN). RELN encodes a signaling protein that plays a pivotal role in the migration of several neuronal cell types and in the development of neural connections. Given these neurodevelopmental functions, recent reports that RELN influences genetic risk for autism are of significant interest. The total data set consists of 218 Caucasian families collected by our group, 85 Caucasian families collected by AGRE, and 68 Caucasian families collected at Tufts University were tested for genetic association of RELN variants to autism. Markers included five single-nucleotide polymorphisms (SNPs) and a repeat in the 5'-untranslated region (5'-UTR). Tests for association in Duke and AGRE families were also performed on four additional SNPs in the genes PSMC2 and ORC5L, which flank RELN. Family-based association analyses (PDT, Geno-PDT, and FBAT) were used to test for association of single-locus markers and multilocus haplotypes with autism. The most significant association identified from this combined data set was for the 5'-UTR repeat (PDT P-value=0.002). These analyses show the potential of RELN as an important contributor to genetic risk in autism.

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Available from: Mike Cuccaro, Sep 30, 2015
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    • "RELN encodes an extracellular glycoprotein that has critical roles in the neuronal migration of cortical layers and synaptic remodeling. Despite several studies failed to find association [30] [31], positive association have been found between polymorphisms in the 5 0 UTR and intron of RELN and ASD [32] [33], and meta-analysis support the association [34]. FOXP2 is a gene important for language development and its mutations have been identified in individuals with speech and language impairment [35]. "
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    ABSTRACT: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic component. The past decade has witnessed tremendous progress in the genetic studies of ASD. In this article, we review the accumulating literatures on the monogenic forms of ASD and chromosomal abnormalities associated with ASD, the genome-wide linkage and association studies, the copy number variation (CNV) and the next generation sequencing (NGS) studies. With more than hundreds of mutations being implicated, the convergent biological pathways are emerging and the genetic landscape of ASD becomes clearer. The genetic studies provide a solid basis for future translational study for better diagnoses, intervention and treatment of ASD.
    Biochemical and Biophysical Research Communications 09/2014; 452(2). DOI:10.1016/j.bbrc.2014.08.108 · 2.30 Impact Factor
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    • "Some of these reports confirmed that certain RELN genetic variants are statistically associated with autism risk (Persico et al., 2001; Bonora et al., 2003; Bartlett et al., 2005; Skaar et al., 2005; Serajee et al., 2006; Ashley-Koch et al., 2007; Li et al., 2008; Holt et al., 2010; Tian, 2012). However, the results from these observations were conflicting rather than conclusive (Krebs et al., 2002; Zhang et al., 2002; Bonora et al., 2003; Devlin et al., 2004; Li et al., 2004; Skaar et al., 2005; Serajee et al., 2006; Dutta et al., 2008; Li et al., 2008; He et al., 2011). Up to date, there are no similar studies on the association of g.296596G > A genetic variant in RELN gene with autism susceptibility. "
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    ABSTRACT: Autism is a childhood neuro-developmental disorder, and Reelin (RELN) is an important candidate gene for influencing autism. This study aimed at investigating the influence of genetic variants of the RELN gene on autism susceptibility. In this study, 205 autism patients and 210 healthy controls were recruited and the genetic variants of the RELN gene were genotyped by the created restriction site-polymerase chain reaction (CRS-PCR) method. The influence of genetic variants on autism susceptibility was analyzed by association analysis, and the g.296596G > A genetic variant in exon10 of the RELN gene was detected. The frequencies of allele/genotype in autistic patients were significantly different from those in healthy controls, and a statistically significant association was detected between this genetic variant and autism susceptibility. Our data lead to the inference that the g.296596G > A genetic variant in the RELN gene has a potential influence on autism susceptibility in the Chinese Han population.
    Genetics and Molecular Biology 12/2013; 36(4):486-9. DOI:10.1590/S1415-47572013005000037 · 1.20 Impact Factor
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    • "To date, a number of studies have investigated association of the SNPs of the RELN gene with autism in various populations (Persico et al., 2001; Krebs et al., 2002; Zhang et al., 2002; Bonora et al., 2003; Devlin et al., 2004; Skaar et al., 2004; Serajee et al., 2006). The conflicting results obtained through these studies demand replication of RELN association studies in larger groups from different populations worldwide. "
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    ABSTRACT: Background: Autism (MIM209850) is a neurodevelopmental disorder characterized by a triad of impairments, namely impairment in social interaction, impaired communication skills, and restrictive and repetitive behavior. A number of family and twin studies have demonstrated that genetic factors play a pivotal role in the etiology of autistic disorder. Various reports of reduced levels of reelin protein in the brain and plasma in autistic patients highlighted the role of the reelin gene (RELN) in autism. There is no such published study on the South African (SA) population. Aims: The aim of the present study was to find the genetic association of intronic rs736707 and exonic rs362691 (single-nucleotide polymorphisms [SNPs] of the RELN gene) with autism in a SA population. Methods: Genomic DNA was isolated from cheek cell swabs from autistic (136) as well as control (208) subjects. The TaqMan(®) Real-Time polymerase chain reaction and genotyping assay was utilized to determine the genotypes. Results: A significant association of SNP rs736707, but not for SNP rs362691, with autism in the SA population is observed. Conclusion: There might be a possible role of RELN in autism, especially for SA populations. The present study represents the first report on genetic association studies on the RELN gene in the SA population.
    Genetic Testing and Molecular Biomarkers 12/2012; 17(2). DOI:10.1089/gtmb.2012.0212 · 1.46 Impact Factor
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