Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene

Bacchelli, Elena; Blasi, Francesca; Biondolillo, Marianna; Lamb, Janine A.; Bonora, Elena; Barnby, Gabrielle; Parr, Jeremy; Beyer, Kim S.; Klauck, Sabine M.; Poustka, Annemarie; Bailey, Anthony; Monaco, Anthony P.; Maestrini, Elena

doi:10.1038/sj.mp.4001340

Cited by 109 publications

(81 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the long arm of chromosome 2, GAD1, NOSTRIN, KCNH7, TBR1, DLX1 and DLX2, were identified for their role in brain function, with several of these genes involved in glutamanergic neural transmission (which is theorised to influence prefrontal cortex functioning; Huntsman et al, 1998). Some of these genes (GAD1, DLX1 & 2, TBR1) have been tested for their association with autism, which is linked to this same region of chromosome 2 (Bacchelli et al, 2003;Rabionet et al, 2004). While association was not supported for autism, it is possible that these genes play a role in cognitive ability.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

et al. 2005

View full text Add to dashboard Cite

A genome-wide linkage scan of 795 microsatellite markers (761 autosomal, 34 X chromosome) was performed on Multidimensional Aptitude Battery subtests and verbal, performance and full scale scores, the WAIS-R Digit Symbol subtest, and two word-recognition tests (Schonell Graded Word Reading Test, Cambridge Contextual Reading Test) highly predictive of IQ. The sample included 361 families comprising 2-5 siblings who ranged in age from 15.7 to 22.2 years; genotype, but not phenotype, data were available for 81% of parents. A variance components analysis which controlled for age and sex effects showed significant linkage for the Cambridge reading test and performance IQ to the same region on chromosome 2, with respective LOD scores of 4.15 and 3.68. Suggestive linkage (LOD score>2.2) for various measures was further supported on chromosomes 6, 7, 11, 14, 21 and 22. Where location of linkage peaks converged for IQ subtests within the same scale, the overall scale score provided increased evidence for linkage to that region over any individual subtest. Association studies of candidate genes, particularly those involved in neural transmission and development, will be directed to genes located under the linkage peaks identified in this study.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

et al. 2005

View full text Add to dashboard Cite

show abstract

“…No clear evidence for association of any of the new variants with AD was found despite relatively high LOD scores from linkage analyses in the assessed samples. 38,[155][156][157] Four independent studies compared two single-nucleotide polymorphisms (SNPs) in the gene for the mitochondrial aspartate/glutamate carrier SLC25A12 in family-based and case-control association studies. Two studies 158,159 found an increased risk for autism associated with the haplotype GG (reverse strand) = CC (sense strand) consisting of SNPs rs2056202 and rs2292813.…”

Section: Chromosomementioning

confidence: 99%

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

2006

View full text Add to dashboard Cite

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.

show abstract

“…Previously, we have identified in a patient with SCZ a de novo exonic microdeletion affecting another member of the RAPGEF family (RAPGEF6) located within a SCZ susceptibility locus at chromosome 5q (15). Mutations in another member of this family (RAPGEF4) have been described in autism (27).…”

Section: Patient Cohortsmentioning

confidence: 99%

Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans

Woodroffe²,

Rodríguez-Murillo³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

143

124

View full text Add to dashboard Cite

To elucidate the genetic architecture of familial schizophrenia we combine linkage analysis with studies of fine-level chromosomal variation in families recruited from the Afrikaner population in South Africa. We demonstrate that individually rare inherited copy number variants (CNVs) are more frequent in cases with familial schizophrenia as compared to unaffected controls and affect almost exclusively genic regions. Interestingly, we find that while the prevalence of rare structural variants is similar in familial and sporadic cases, the type of variants is markedly different. In addition, using a high-density linkage scan with a panel of nearly 2,000 markers, we identify a region on chromosome 13q34 that shows genome-wide significant linkage to schizophrenia and show that in the families not linked to this locus, there is evidence for linkage to chromosome 1p36. No causative CNVs were identified in either locus. Overall, our results from approaches designed to detect risk variants with relatively low frequency and high penetrance in a well-defined and relatively homogeneous population, provide strong empirical evidence supporting the notion that multiple genetic variants, including individually rare ones, that affect many different genes contribute to the genetic risk of familial schizophrenia. They also highlight differences in the genetic architecture of the familial and sporadic forms of the disease.rare mutations ͉ chromosome 13q34 ͉ chromosome 1p36 ͉ RAPGEF gene family

show abstract

Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene

Cited by 109 publications

References 38 publications

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

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

Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans

Contact Info

Product

Resources

About