23 research outputs found
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A Pooled Genome-Wide Association Study of Asperger Syndrome.
Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.This work was funded by grants to SBC from the Nancy Lurie Marks Family Foundation, the Medical Research Council (MRC) UK, Target Autism Genome, and the Autism Research Trust (ART). LM and SEF were supported by the Max Planck Society. VW is funded by St. John’s College, Cambridge and the Cambridge Commonwealth Trust.This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013120
Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.
Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability
Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus
Idiopathic congenital nystagmus (ICN) is characterised by involuntary, periodic, predominantly horizontal, oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 ICN singleton cases (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina suggesting a specific role in the control of eye movement and gaze stability
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A Genome Wide Association Study of Mathematical Ability Reveals an Association at Chromosome 3q29, a Locus Associated with Autism and Learning Difficulties:A Preliminary Study
Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419) versus low (n = 183) mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of p<1.5×10-5, 12 SNPs from the pooled association analysis were individually genotyped in 542 of the participants and analyzed to validate the initial associations (lowest p-value 1.14 ×10-6). In this analysis, one of the SNPs (rs789859) showed significant association after Bonferroni correction, and four (rs10873824, rs4144887, rs12130910 rs2809115) were nominally significant (lowest p-value 3.278 × 10-4). Three of the SNPs of interest are located within, or near to, known genes (FAM43A, SFT2D1, C14orf64). The SNP that showed the strongest association, rs789859, is located in a region on chromosome 3q29 that has been previously linked to learning difficulties and autism. rs789859 lies 1.3 kbp downstream of LSG1, and 700 bp upstream of FAM43A, mapping within the potential promoter/regulatory region of the latter. To our knowledge, this is only the second study to investigate the association of genetic variants with mathematical ability, and it highlights a number of interesting markers for future study
Pearson's correlation of real allele frequencies in total sample (calculated from individual genotyping,y-axis) and frequency estimates from pooled DNA (mean RAS-scores of the 15 pools, x-axis) of 32 SNPs (r  =  0.8424).
<p>Pearson's correlation of real allele frequencies in total sample (calculated from individual genotyping,y-axis) and frequency estimates from pooled DNA (mean RAS-scores of the 15 pools, x-axis) of 32 SNPs (r  =  0.8424).</p
Association results of SNPs associated at a significance value of 0.05 or less in the individual genotyping stage, along with their pooling stage results.
<p>SNPs written in bold are significant after correcting for multiple testing.</p
15 SNPs chosen for individual genotyping with the P-values from the pooling stage.
a<p>Indicates SNPs that did not survive quality control measures to be included in the association validation analysis.</p
Graphical summary of association results from the genome-wide screen of pooled samples.
<p>X-axis represents the chromosome position; y-axis shows -log10 of the P-value obtained for each SNP.</p
Quantile-quantile plot of the SNPs tested in the pooled DNA association stage.
<p>Quantile-quantile plot of the SNPs tested in the pooled DNA association stage.</p
Manhattan plot of the SNPs tested in the pooled DNA association stage.
<p>Manhattan plot of the SNPs tested in the pooled DNA association stage.</p