Publications

Abstract

Lateralization is a defining characteristic of the human brain, often studied through localized approaches that focus on interhemispheric differences between homologous pairs of regions. It is also important to emphasize an integrative perspective of global brain asymmetry, in which hemispheric differences are understood through global patterns across the entire brain.

Abstract

Hemispheric brain asymmetry is a basic organizational principle of the human brain and has been implicated in various psychiatric conditions, including autism spectrum disorder. Brain asymmetry is not a uniquely human feature and is observed in other species such as the mouse. Yet, asymmetry patterns are generally nuanced, and substantial sample sizes are required to detect these patterns. In this pre-registered study, we use a mouse dataset from the Province of Ontario Neurodevelopmental Network, which comprises structural MRI data from over 2000 mice, including genetic models for autism spectrum disorder, to reveal the scope and magnitude of hemispheric asymmetry in the mouse. Our findings demonstrate the presence of robust hemispheric asymmetry in the mouse brain, such as larger right hemispheric volumes towards the anterior pole and larger left hemispheric volumes toward the posterior pole, opposite to what has been shown in humans. This suggests the existence of species-specific traits. Further clustering analysis identified distinct asymmetry patterns in autism spectrum disorder models, a phenomenon that is also seen in atypically developing participants. Our study shows potential for the use of mouse models in studying the biological bases of typical and atypical brain asymmetry but also warrants caution as asymmetry patterns seem to differ between humans and mice.

Abstract

Left-right asymmetry is an important aspect of human brain organization for functions including language and hand motor control, which can be altered in some psychiatric traits. The last five years have seen rapid advances in the identification of specific genes linked to variation in asymmetry of the human brain and/or handedness. These advances have been driven by a new generation of large-scale genome-wide association studies, carried out in samples ranging from roughly 16,000 to over 1.5 million participants. The implicated genes tend to be most active in the embryonic and fetal brain, consistent with early developmental patterning of brain asymmetry. Several of the genes encode components of microtubules, or other microtubule-associated proteins. Microtubules are key elements of the internal cellular skeleton (cytoskeleton). A major challenge remains to understand how these genes affect, or even induce, the brain’s left-right axis. Several of the implicated genes have also been associated with psychiatric or neurological disorders, and polygenic dispositions to autism and schizophrenia have been associated with structural brain asymmetry. Knowledge of developmental mechanisms that lead to hemispheric specialization may ultimately help to define etiologic subtypes of brain disorders.

Abstract

First paragraph: The study of the transmission of sign languages can give novel insights into the transmission of spoken languages1 and, more generally, into gene–culture coevolution. Over the years, several papers related to the persistence of sign language have been
reported.2–6 All of these studies have emphasized the role of assortative (non-random) mating by deafness state (ie, a tendency for deaf individuals to partner together) for increasing the frequency of recessive deafness, and hence for the persistence of sign language in a population.

Abstract

Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype

Abstract

Autism is characterized by impairments in reciprocal social interaction and communication, and restricted and sterotyped patterns of interests and activities. Developmental difficulties are apparent before 3 years of age and there is evidence for strong genetic influences most likely involving more than one susceptibility gene. A two-stage genome search for susceptibility loci in autism was performed on 87 affected sib pairs plus 12 non-sib affected relative-pairs, from a total of 99 families identified by an international consortium. Regions on six chromosomes (4, 7, 10, 16, 19 and 22) were identified which generated a multipoint maximum lod score (MLS) > 1. A region on chromosome 7q was the most significant with an MLS of 3.55 near markers D7S530 and D7S684 in the subset of 56 UK affected sib-pair families, and an MLS of 2.53 in all 87 affected sib-pair families. An area on chromosome 16p near the telomere was the next most significant, with an MLS of 1.97 in the UK families, and 1.51 in all families. These results are an important step towards identifying genes predisposing to autism; establishing their general applicability requires further study.