Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder

Persico, Antonio M.; D’Agruma, Leonardo; Maiorano, Nunzia; Totaro, Angela; Militerni, Roberto; Bravaccio, Carmela; Wassink, Thomas H.; Schneider, Cindy; Melmed, Raun D.; Trillo, Simona; Montecchi, Francesco; Palermo, Mark T.; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Reichelt, Karl L.; Conciatori, Monica; Marino, Ramona; Quattrocchi, Carlo Cosimo; Baldi, Alfonso; Zelante, Leopoldo; Gasparini, Paolo; Keller, Flavio

doi:10.1038/sj.mp.4000850

Cited by 309 publications

(262 citation statements)

References 57 publications

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“…Three studies did find an association, [176][177][178] five other studies of comparable size and power did not find an association of the 5 0 UTR trinucleotide or other variants with AD. [179][180][181][182][183] The first positive finding 176 reported an association with the relatively rare longer alleles ( > 10) of the 5 0 UTR trinucleotide polymorphism with AD. However, in another study, 178 the most common repeat 10 was over-represented in AD.…”

Section: Chromosomementioning

confidence: 84%

The genetics of autistic disorders and its clinical relevance: a review of the literature

2006

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Twin and family studies in autistic disorders (AD) have elucidated a high heritability of the narrow and broad phenotype of AD. In this review on the genetics of AD, we will initially delineate the phenotype of AD and discuss aspects of differential diagnosis, which are particularly relevant with regard to the genetics of autism. Cytogenetic and molecular genetic studies will be presented in detail, and the possibly involved aetiopathological pathways will be described. Implications of the different genetic findings for genetic counselling will be mentioned.

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Section: Chromosomementioning

confidence: 84%

The genetics of autistic disorders and its clinical relevance: a review of the literature

2006

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“…region before the start codon, have reached conflicting results. [43][44][45][46][47][48][49] This may reflect only the common pattern of nonreplication of early claims from small studies 50 or a modest effect may still be present. A large study should be conducted on this association.…”

Section: Discussionmentioning

confidence: 99%

A heterogeneity-based genome search meta-analysis for autism-spectrum disorders

et al. 2005

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Autism and autism-spectrum disorders exhibit high heritability, although specific susceptibility genes still remain largely elusive. We performed a heterogeneity-based genome search meta-analysis (HEGESMA) of nine genome scans on autism or autism-spectrum disorders. Each genome scan was separated in 30 cM bins and the maximum linkage statistic from each bin was ranked. Significance for each bin's average rank and for between-scan heterogeneity (dis-similarity in the average ranks) was obtained through Monte Carlo tests. For autism, data from 771 affected sibpairs were synthesized across six separate genome scans. Region 7q22-q32 reached genome-wide significance both in weighted and unweighted analyses, with evidence for significantly low between-scan heterogeneity. The flanking chromosomal region 7q32-qter reached the less stringent threshold of suggestive significance, with no evidence for low between-scan heterogeneity. For autism-spectrum disorders (634 affected sibpairs from five separate scans), no chromosomal region reached genome-wide significance. However, suggestive significance was reached for the chromosomal regions 17p11.2-q12 and 10p12-q11.1 in weighted analyses. There was evidence for significantly high between-scan heterogeneity for the former region. The meta-analysis suggests that the 7q22-q32 region should be further scrutinized for autism susceptibility genes, while autism-spectrum disorders seem to have quite diverse linkage signals across scans, possibly suggesting genetic heterogeneity across subsyndromes and subpopulations.

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“…Genetic studies in human populations have suggested that the RELN gene may be associated with autism susceptibility, [146][147][148][149] although not all findings have been positive. [150][151][152] Fatemi et al 153,154 have shown that levels of RELN mRNA and Reelin protein are significantly deficient in the brain of autistic subjects.…”

Section: Autism Candidate Genes and Synaptic Functionmentioning

confidence: 99%

Advances in behavioral genetics: mouse models of autism

2007

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Autism is a neurodevelopmental syndrome with markedly high heritability. The diagnostic indicators of autism are core behavioral symptoms, rather than definitive neuropathological markers. Etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In this review, we focus on genetic pathways with multiple members represented in autism candidate gene lists. Many of these pathways can also be impinged upon by environmental risk factors associated with the disorder. The mouse model system provides a method to experimentally manipulate candidate genes for autism susceptibility, and to use environmental challenges to drive aberrant gene expression and cell pathology early in development. Mouse models for fragile X syndrome, Rett syndrome and other disorders associated with autistic-like behavior have elucidated neuropathology that might underlie the autism phenotype, including abnormalities in synaptic plasticity. Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, relevant to findings in autistic populations. Advances have included the evaluation of mouse models with behavioral assays designed to reflect disease symptoms, including impaired social interaction, communication deficits and repetitive behaviors, and the symptom onset during the neonatal period. Research focusing on the effect of gene-by-gene interactions or genetic susceptibility to detrimental environmental challenges may further understanding of the complex etiology for autism.

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Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder

Cited by 309 publications

References 57 publications

The genetics of autistic disorders and its clinical relevance: a review of the literature

The genetics of autistic disorders and its clinical relevance: a review of the literature

A heterogeneity-based genome search meta-analysis for autism-spectrum disorders

Advances in behavioral genetics: mouse models of autism

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