12 research outputs found

    Committed Partners and Inheritance: An Empirical Study

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    There is widespread recognition that U.S. households have changed dramatically in the latter half of the twentieth century. 1 The changes include an increased number of blended families, 2 single-parent households, 3 and unmarried same-sex and opposite-sex committed couples, including some with children. 4 The transformation taking place in U.S. households implicates property law and vice versa. In recognition of the changing U.S. household and the symbiotic relationship between wealth transmission and family, we undertook an empirical study designed to assess public attitudes about the inclusion of surviving committed partners as heirs. This Article reports our findings

    Quantitative genome-wide association study of six phenotypic subdomains identifies novel genome-wide significant variants in autism spectrum disorder

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    Autism spectrum disorders (ASD) are highly heritable and are characterized by deficits in social communication and restricted and repetitive behaviors. Twin studies on phenotypic subdomains suggest a differing underlying genetic etiology. Studying genetic variation explaining phenotypic variance will help to identify specific underlying pathomechanisms. We investigated the effect of common variation on ASD subdomains in two cohorts including >2500 individuals. Based on the Autism Diagnostic Interview-Revised (ADI-R), we identified and confirmed six subdomains with a SNP-based genetic heritability h2SNP = 0.2–0.4. The subdomains nonverbal communication (NVC), social interaction (SI), and peer interaction (PI) shared genetic risk factors, while the subdomains of repetitive sensory-motor behavior (RB) and restricted interests (RI) were genetically independent of each other. The polygenic risk score (PRS) for ASD as categorical diagnosis explained 2.3–3.3% of the variance of SI, joint attention (JA), and PI, 4.5% for RI, 1.2% of RB, but only 0.7% of NVC. We report eight genome-wide significant hits—partially replicating previous findings—and 292 known and novel candidate genes. The underlying biological mechanisms were related to neuronal transmission and development. At the SNP and gene level, all subdomains showed overlap, with the exception of RB. However, no overlap was observed at the functional level. In summary, the ADI-R algorithm-derived subdomains related to social communication show a shared genetic etiology in contrast to restricted and repetitive behaviors. The ASD-specific PRS overlapped only partially, suggesting an additional role of specific common variation in shaping the phenotypic expression of ASD subdomains

    Common variants in genes of the postsynaptic FMRP signalling pathway are risk factors for autism spectrum disorders.

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    International audienceAutism spectrum disorders (ASD) are heterogeneous disorders with a high heritability and complex genetic architecture. Due to the central role of the fragile X mental retardation gene 1 protein (FMRP) pathway in ASD we investigated common functional variants of ASD risk genes regulating FMRP. We genotyped ten SNPs in two German patient sets (N = 192 and N = 254 families, respectively) and report association for rs7170637 (CYFIP1; set 1 and combined sets), rs6923492 (GRM1; combined sets), and rs25925 (CAMK4; combined sets). An additional risk score based on variants with an odds ratio (OR) >1.25 in set 1 and weighted by their respective log transmitted/untransmitted ratio revealed a significant effect (OR 1.30, 95 % CI 1.11-1.53; P = 0.0013) in the combined German sample. A subsequent meta-analysis including the two German samples, the "Strict/European" ASD subsample of the Autism Genome Project (1,466 families) and a French case/control (541/366) cohort showed again association of rs7170637-A (OR 0.85, 95 % CI 0.75-0.96; P = 0.007) and rs25925-G (OR 1.31, 95 % CI 1.04-1.64; P = 0.021) with ASD. Functional analyses revealed that these minor alleles predicted to alter splicing factor binding sites significantly increase levels of an alternative mRNA isoform of the respective gene while keeping the overall expression of the gene constant. These findings underpin the role of ASD candidate genes in postsynaptic FMRP regulation suggesting that an imbalance of specific isoforms of CYFIP1, an FMRP interaction partner, and CAMK4, a transcriptional regulator of the FMRP gene, modulates ASD risk. Both gene products are related to neuronal regulation of synaptic plasticity, a pathomechanism underlying ASD and may thus present future targets for pharmacological therapies in ASD

    Ethanol Ultra-Light Aircraft (Spring 2002) IPRO 317: Ethanol_Utralight_IPRO317_Spring2002_Final_Presentation

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    This semester will conclude the conversion of a Quicksilver MXII ultralight airplane to operate on E85 fuel (a mixture of 85% ethanol, 15% gasoline). The 2-stroke engine will be tested on a dynamometer for compatibility and performance when using this fuel minimizes with a specially formulated lubricant. After that, it will be mounted back on the aircraft and tested in flightSponsorship: NAProject Plan for IPRO 317: Ethanol Ultralight Aircraft for the Spring 2002 semeste
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