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

Novel and flexible approach to access the open ocean: Uses of sailing research vessel Lady Amber during SPURS-2.

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Rainville, L., Centurioni, L. R., Asher, W. E., Clayson, C. A., Drushka, K., Edson, J. B., Hodges, B. A., Hermann, V., Farrar, J. T., Schanze, J. J., & Shcherbina, A. Y. Novel and flexible approach to access the open ocean: Uses of sailing research vessel Lady Amber during SPURS-2. Oceanography, 32(2), (2019): 116-121, doi: 10.5670/oceanog.2019.219.SPURS-2 (Salinity Processes in the Upper-ocean Regional Study 2) used the schooner Lady Amber, a small sailing research vessel, to deploy, service, maintain, and recover a variety of oceanographic and meteorological instruments in the eastern Pacific Ocean. Low operational costs allowed us to frequently deploy floats and drifters to collect data necessary for resolving the regional circulation of the eastern tropical Pacific. The small charter gave us the opportunity to deploy drifters in locations chosen according to current conditions, to recover and deploy various autonomous instruments in a targeted and adaptive manner, and to collect additional near-surface and atmospheric measurements in the remote SPURS-2 region.Tragically, Lady Amber Captain Peter Flanagan passed away on March 15, 2016, after the initial transit. This was a big loss for his friends and crew—his enthusiasm will be sorely missed. We acknowledge the owner and crew of Lady Amber for remaining committed to the SPURS-2 work. This work would not have been possible without Captain Arran Flanagan and Captain Ryan Struthers and the capable crew of Lady Amber. This project was supported by NASA grant NNX15AT40G. We also acknowledge the contribution of Justin Burnett, Jesse Dosher, and Aaron Paget to the design and installation of the LAPS, and the support and cooperation from all the SPURS-2 PIs

A Whole-Genome Scan and Fine-Mapping Linkage Study of Auditory-Visual Synesthesia Reveals Evidence of Linkage to Chromosomes 2q24, 5q33, 6p12, and 12p12

Synesthesia, a neurological condition affecting between 0.05%–1% of the population, is characterized by anomalous sensory perception and associated alterations in cognitive function due to interference from synesthetic percepts. A stimulus in one sensory modality triggers an automatic, consistent response in either another modality or a different aspect of the same modality. Familiality studies show evidence of a strong genetic predisposition; whereas initial pedigree analyses supported a single-gene X-linked dominant mode of inheritance with a skewed F:M ratio and a notable absence of male-to-male transmission, subsequent analyses in larger samples indicated that the mode of inheritance was likely to be more complex. Here, we report the results of a whole-genome linkage scan for auditory-visual synesthesia with 410 microsatellite markers at 9.05 cM density in 43 multiplex families (n = 196) with potential candidate regions fine-mapped at 5 cM density. Using NPL and HLOD analysis, we identified four candidate regions. Significant linkage at the genome-wide level was detected to chromosome 2q24 (HLOD = 3.025, empirical genome-wide p = 0.047). Suggestive linkage was found to chromosomes 5q33, 6p12, and 12p12. No support was found for linkage to the X chromosome; furthermore, we have identified two confirmed cases of male-to-male transmission of synesthesia. Our results demonstrate that auditory-visual synesthesia is likely to be an oligogenic disorder subject to multiple modes of inheritance and locus heterogeneity. This study comprises a significant step toward identifying the genetic substrates underlying synesthesia, with important implications for our understanding of the role of genes in human cognition and perception

Absolute pitch exhibits phenotypic and genetic overlap with synesthesia

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CnvHap: An integrative population and haplotype-based multiplatform model of SNPs and CNVs

Although genome-wide association studies have uncovered single-nucleotide polymorphisms (SNPs) associated with complex disease, these variants account for a small portion of heritability. Some contribution to this 'missing heritability' may come from copy-number variants (CNVs), in particular rare CNVs; but assessment of this contribution remains challenging because of the difficulty in accurately genotyping CNVs, particularly small variants. We report a population-based approach for the identification of CNVs that integrates data from multiple samples and platforms. Our algorithm, cnvHap, jointly learns a chromosome-wide haplotype model of CNVs and cluster-based models of allele intensity at each probe. Using data for 50 French individuals assayed on four separate platforms, we found that cnvHap correctly detected at least 14% more deleted and 50% more amplified genotypes than PennCNV or QuantiSNP, with an 82% and 115% improvement for aberrations containing 10 probes. Combining data from multiple platforms additionally improved sensitivity