Rare variants in axonogenesis genes connect three families with sound–color synesthesia

Synesthesia is a rare nonpathological phenomenon where stimulation of one sense automatically provokes a secondary perception in another. Hypothesized to result from differences in cortical wiring during development, synesthetes show atypical structural and functional neural connectivity, but the underlying molecular mechanisms are unknown. The trait also appears to be more common among people with autism spectrum disorder and savant abilities. Previous linkage studies searching for shared loci of large effect size across multiple families have had limited success. To address the critical lack of candidate genes, we applied whole-exome sequencing to three families with sound–color (auditory–visual) synesthesia affecting multiple relatives across three or more generations. We identified rare genetic variants that fully cosegregate with synesthesia in each family, uncovering 37 genes of interest. Consistent with reports indicating genetic heterogeneity, no variants were shared across families. Gene ontology analyses highlighted six genes—COL4A1, ITGA2, MYO10, ROBO3, SLC9A6, and SLIT2—associated with axonogenesis and expressed during early childhood when synesthetic associations are formed. These results are consistent with neuroimaging-based hypotheses about the role of hyperconnectivity in the etiology of synesthesia and offer a potential entry point into the neurobiology that organizes our sensory experiences

Genetic and environmental contributions to stability in loneliness throughout childhood.

Heritability estimates based on two small cross-sectional studies in children indicate that the genetic contribution to individual differences in loneliness is approximately 50%. A recent study estimated the genetic contribution to variation in loneliness in adults to be 48%. The current study aims to replicate and expand these findings by conducting longitudinal analyses in order to study causes of individual differences in stability of loneliness throughout childhood. Univariate and multivariate longitudinal analyses are conducted in a large sample of young Dutch twins. Information on loneliness comes from maternal ratings on the Child Behavior Checklist. Using an average score of loneliness over ages 7, 10, and 12, results from the two previous studies are replicated and a heritability estimate of 45% is found. The remaining variance is accounted for by shared environmental influences (12%), and non-shared environmental influences (43%). The long-itudinal analyses, however, show that heritability is 58% at age 7, 56% at age 10, but drops to 26% at age 12. A parallel increase in influences of shared family environment is observed, explaining 6% of the variance at age 7, 8% at age 10 and 35% at age 12. The remaining variance is explained by relatively stable influences of nonshared environmental factors. Stability in loneliness is high, with phenotypic correlations in the range of 0.51-0.69. This phenotypic stability is mainly caused by genetic and nonshared environmental influences. The results indicate the importance of both innate as well as nonshared environmental factors for individual differences in loneliness. Further, different results between causes of individual differences for the average score of loneliness and results for age 12 from the longitudinal analyses, indicate the importance of longitudinal analyses with data at well-defined ages. © 2007 Wiley-Liss, Inc

Endogenous siRNAs promote proteostasis and longevity in germline-less Caenorhabditis elegans.

How lifespan and the rate of aging are set is a key problem in biology. Small RNAs are conserved molecules that impact diverse biological processes through the control of gene expression. However, in contrast to miRNAs, the role of endo-siRNAs in aging remains unexplored. Here, by combining deep sequencing and genomic and genetic approaches in Caenorhabditis elegans, we reveal an unprecedented role for endo-siRNA molecules in the maintenance of proteostasis and lifespan extension in germline-less animals. Furthermore, we identify an endo-siRNA-regulated tyrosine phosphatase, which limits the longevity of germline-less animals by restricting the activity of the heat shock transcription factor HSF-1. Altogether, our findings point to endo-siRNAs as a link between germline removal and the HSF-1 proteostasis and longevity-promoting somatic pathway. This establishes a role for endo siRNAs in the aging process and identifies downstream genes and physiological processes that are regulated by the endo siRNAs to affect longevity

Oxygen and Carbon Dioxide Rhythms Are Circadian Clock Controlled and Differentially Directed by Behavioral Signals

This is the author accepted manuscript. The final version is available from Elsevier (Cell Press).Daily rhythms in animal physiology are driven by endogenous circadian clocks in part through rest-activity and feeding-fasting cycles. Here, we examined principles that govern daily respiration. We monitored oxygen consumption and carbon dioxide release, as well as tissue oxygenation in freely moving animals to specifically dissect the role of circadian clocks and feeding time on daily respiration. We found that daily rhythms in oxygen and carbon dioxide are clock controlled and that time-restricted feeding restores their rhythmicity in clock-deficient mice. Remarkably, day-time feeding dissociated oxygen rhythms from carbon dioxide oscillations, whereby oxygen followed activity, and carbon dioxide was shifted and aligned with food intake. In addition, changes in carbon dioxide levels altered clock gene expression and phase shifted the clock. Collectively, our findings indicate that oxygen and carbon dioxide rhythms are clock controlled and feeding regulated and support a potential role for carbon dioxide in phase resetting peripheral clocks upon feeding.British Heart FoundationEuropean Research CouncilEuropean Union, Seventh Framework Program, Marie Curie Action

Objectum sexuality: a sexual orientation linked with autism and synaesthesia

Objectum-sexuality (OS) is a sexual orientation which has received little attention in the academic literature. Individuals who identify as OS experience emotional, romantic and/or sexual feelings towards inanimate objects (e.g. a bridge, a statue). We tested 34 OS individuals and 88 controls, and provide the first empirical evidence that OS is linked to two separate neurodevelopmental traits - autism and synaesthesia. We show that OS individuals possess significantly higher rates of diagnosed autism and significantly stronger autistic traits compared to controls, as well as a significantly higher prevalence of synaesthesia, and significant synaesthetic traits inherent in the nature of their attractions. Our results suggest that OS may encapsulate autism and synaesthesia within its phenomenology. Our data speak to debates concerning the biological underpinnings of sexuality, to models of autism and synaesthesia, and to psychological and philosophical models of romantic love