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Abstract Correction to Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ: The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. BMC Genomics 2007, 8:320.

Abstract Background Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships. Results This yields a total of 369 proteins (29 in worm, 66 in fly, 135 in mouse and 139 in human), many of them of unknown function. We group eLRR proteins into several classes: those with only LRRs, those that cluster with Toll-like receptors (Tlrs), those with immunoglobulin or fibronectin-type 3 (FN3) domains and those with some other domain. These groups show differential patterns of expansion and diversification across species. Our analyses reveal several clusters of novel genes, including two Elfn genes, encoding transmembrane proteins with eLRRs and an FN3 domain, and six genes encoding transmembrane proteins with eLRRs only (the Elron cluster). Many of these are expressed in discrete patterns in the developing mouse brain, notably in the thalamus and cortex. We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system. Conclusion This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.

Recent research into synaesthesia has highlighted the role of learning, yet synaesthesia is clearly a genetic condition. Here we ask how can the idea that synaesthesia reflects innate, genetic differences be reconciled with models that suggest it is driven by learning. A number of lines of evidence suggest that synaesthesia relies on, or at least interacts with, processes of multisensory integration that are common across all people. These include multisensory activations that arise in early regions of the brain as well as feedback from longer-term cross-modal associations generated in memory. These cognitive processes may interact independently to influence the phenomenology of the synaesthetic experience, as well as the individual differences within particular types of synaesthesia. The theoretical framework presented here is consistent with both an innate difference as the fundamental driver of the condition of synaesthesia, and with experiential and semantic influences on the eventual phenotype that emerges. In particular, it proposes that the internally generated synaesthetic percepts are treated similarly to other sensory information as the brain is learning the multisensory attributes of objects and developing cross-modal associations that merge in the concept of the object. [ABSTRACT FROM AUTHOR]

The term neurodevelopmental disorder encompasses a wide range of diseases, including recognizably distinct syndromes known to be caused by very rare mutations in specific genes or chromosomal loci, and also much more common disorders such as schizophrenia, autism spectrum disorders, and idiopathic epilepsy and mental retardation. After decades of frustration, the past couple of years have suddenly seen tremendous progress in unravelling the genetics of these common disorders. These findings have led to a paradigm shift in our conception of the genetic architecture of common neurodevelopmental disease, highlighting the importance of individual, rare mutations and overlapping genetic aetiology of various disorders. They have also converged on specific neurodevelopmental pathways, providing insights into pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Synaesthesia is a heritable condition of involuntary sensory cross-activation whereby the presentation of a particular stimulus elicits a secondary sensory-perceptual experience. It is thought to be caused by aberrant cross-activation of one cortical area by another, but models differ as to whether this reflects functional or structural differences in the brains of synaesthetes. Here we consider these models in light of recent experimental findings and argue for structural differences in the brains of synaesthetes, which might be more widespread than expected. We also discuss several plausible developmental mechanisms that could link a putative genetic variant to altered cortical connectivity and illustrate how synaesthesia could be an informative model to investigate how patterns of connectivity between cortical areas are established. [Copyright &y& Elsevier]

In this article the author reflects upon progress made by developmental neurobiologists in neurodevelopment and psychopathology. The author discusses discoveries related to developmental neurobiology and psychiatry and mentions different genes with similar clinical phenotype. The author also explains large number of disease susceptibility in reference to evolutionary genetics.

Abstract: The term synaesthesia has been applied to a range of different sensory-perceptual and cognitive experiences, yet how these experiences are related to each other is not well understood. Not only are there disparate types of synaesthesia, but even within types there are vast individual differences in the way that stimuli induce synaesthesia and in the subjective synaesthetic experience. An investigation of the inheritance patterns of different types of synaesthesia is likely to elucidate whether a single underlying mechanism can explain all types. This study is the first to systematically survey all types of synaesthesia within a familial framework. We recruited 53 synaesthetes and 42% of these probands reported a first-degree relative with synaesthesia. We then directly contacted as many first-degree relatives as possible and collected complete data on synaesthetic status for all family members for 17 families. We found that different types of synaesthesia can occur within the same family and that the qualitative nature of the experience can differ between family members. Our findings strongly indicate that various types of synaesthesia are fundamentally related at the genetic level, but that the explicit associations and the individual differences between synaesthetes are influenced by other factors. Synaesthesia thus provides a good model to explore the interplay of all these factors in the development of cognitive traits in general. [Copyright &y& Elsevier]