Genomic and epigenetic evidence for oxytocin receptor deficiency in autism

<p>Abstract</p> <p>Background</p> <p>Autism comprises a spectrum of behavioral and cognitive disturbances of childhood development and is known to be highly heritable. Although numerous approaches have been used to identify genes implicated in the development of autism, less than 10% of autism cases have been attributed to single gene disorders.</p> <p>Methods</p> <p>We describe the use of high-resolution genome-wide tilepath microarrays and comparative genomic hybridization to identify copy number variants within 119 probands from multiplex autism families. We next carried out DNA methylation analysis by bisulfite sequencing in a proband and his family, expanding this analysis to methylation analysis of peripheral blood and temporal cortex DNA of autism cases and matched controls from independent datasets. We also assessed oxytocin receptor (OXTR) gene expression within the temporal cortex tissue by quantitative real-time polymerase chain reaction (PCR).</p> <p>Results</p> <p>Our analysis revealed a genomic deletion containing the oxytocin receptor gene, <it>OXTR </it>(MIM accession no.: 167055), previously implicated in autism, was present in an autism proband and his mother who exhibits symptoms of obsessive-compulsive disorder. The proband's affected sibling did not harbor this deletion but instead may exhibit epigenetic misregulation of this gene through aberrant gene silencing by DNA methylation. Further DNA methylation analysis of the CpG island known to regulate <it>OXTR </it>expression identified several CpG dinucleotides that show independent statistically significant increases in the DNA methylation status in the peripheral blood cells and temporal cortex in independent datasets of individuals with autism as compared to control samples. Associated with the increase in methylation of these CpG dinucleotides is our finding that <it>OXTR </it>mRNA showed decreased expression in the temporal cortex tissue of autism cases matched for age and sex compared to controls.</p> <p>Conclusion</p> <p>Together, these data provide further evidence for the role of OXTR and the oxytocin signaling pathway in the etiology of autism and, for the first time, implicate the epigenetic regulation of <it>OXTR </it>in the development of the disorder.</p> <p>See the related commentary by Gurrieri and Neri: <url>http://www.biomedcentral.com/1741-7015/7/63</url></p

Evaluating Potential Land Use of Utility-Scale Photovoltaics (Solar Panels) on Farmland in Tennessee

Photovoltaic (PV) cells, commonly referred to as solar panels, absorb energy from sunlight and convert it to electricity. PV energy generation has increased drastically in the United States (U.S.) in the last decade, growing from 26.5 gigawatt-hours in 2014 to over 207 gigawatt-hours in the last 12 months, or from 0.6% to 4.8% of total U.S. electricity production (U.S. Energy Information Administration, 2023a). The combination of increasing cost competitiveness of PV energy generation (U.S. Department of Energy [DOE], 2021) and efforts to decarbonize the U.S. electric grid suggest even more rapid growth. For example, the U.S. DOE (2021) projects that solar generation could grow to as much as 40% of the U.S. electricity supply by 2035, given aggressive decarbonization policies. At a more local level, the Tennessee Valley Authority (TVA) has set a goal of adding 10 gigawatts (GWs) of solar production capacity from 2022 to 2035 (Tennessee Valley Authority, 2023b). The rapid production growth coupled with aggressive targets for decarbonization and increased solar capacity has focused attention on the amount of land currently being converted to PV energy production and the amount that will ultimately be needed to accommodate future growth. This report attempts to quantify the amount of land currently used for utility-scale PV energy production in Tennessee and to project the amount likely to be used under different scenarios for future growth. More specifically, this report estimates the amount of land in Tennessee used by: (i) existing utility-scale PV production, (ii) contracted but not yet operational utility-scale PV production, and (iii) utility-scale PV production if TVA were to reach its PV electricity generation goals. Given that farmland could be a location of PV electricity production, the report considers the possible effects of growth on the amount of available farmland in Tennessee. In Tennessee, operational utility-scale PV production currently produces 344 megawatts (MWs) of energy (TVA, 2023a). Contracted, but not yet operational, utility-scale PV production in Tennessee will account for another 1,130 MWs of energy (TVA, 2023a). Following industry and academic literature (e.g., Solar Energy Industries Association, 2023; Bolinger and Bolinger 2022), a range of 5.56 to 10 acres per MW of generated power was used to estimate PV land use. Thus, current operational and contracted utility-scale PV facilities in Tennessee would generate 1,474 MWs of energy and require 8,197 to 14,743 acres of land. Tennessee has 26.4 million acres of land and 10.8 million acres of farmland (USDA, 2023). Therefore, operational and contracted utility-scale PV land use equates to 0.031 to 0.056% of Tennessee’s total landmass or 0.076 to 0.137% of Tennessee’s farmland if all these facilities were located on farmland. If by 2035 TVA reached their sustainability goal and added an additional 10 GWs of PV generation to the existing 344 MWs of PV production in Tennessee, and assuming that TVA placed all PV developments in Tennessee, 57,514 to 103,443 acres of land would be required for utility-scale PV installments (i.e., an amount equivalent to 0.22 to 0.39% of Tennessee land or 0.53 to 0.96% of Tennessee farmland if exclusively placed on farmland). However, not all of this additional production would be located in Tennessee, which occupies a little more than half of TVA’s 80,000 square mile service region. To provide greater context, this report also contains information on the location of existing and contracted utility-scale PV developments, the extent of Tennessee farmland being converted to other uses, PV development considerations for agricultural communities, and the potential for collocation of PV power generation and agricultural production, or what is commonly referred to as agrivoltaics

UBC Rethink Silviculture Discussion Paper

This whitepaper summarizes information sources, discussions and feedback from practitioners, organized into seven themes each of which concludes with some recommendations for policy and practice improvements on the question of how to better link silviculture strategies to forest-level planning and timber supply analysis.Forestry, Faculty ofUnreviewedFacultyGraduat

Accelerated head growth in early development of individuals with autism

Macrocephaly is one of the most consistent physical findings reported in autistic individuals. Previous studies attempted to determine if macrocephaly is associated with risk for autism. This study hypothesizes that an abnormal acceleration in head growth during early development, rather than macrocephaly, is associated with autism risk. To investigate this hypothesis, head circumference data were examined in 251 individuals from 82 multiplex (at least two individuals with autism) and 113 sporadic (no family history) families with autism. This examination included longitudinal measurements for 79 individuals. Nineteen percent of the original 251 individuals were found to have macrocephaly (head circumference >97%). Abnormal acceleration in head growth was defined as an increase of 25 or more percentile points in head circumference between two consecutive measurements. Thirty-five percent of individuals with multiple head circumference records had an abnormal increase in head circumference. Furthermore, autistic individuals with accelerated head growth in early childhood displayed higher levels of adaptive functioning and less social impairment. This study confirms the presence of abnormal acceleration in head growth during the first and second months of life in a subgroup of autistic individuals

Factor analysis of restricted and repetitive behaviors in autism using the Autism Diagnostic Interview-R

The current study examined the factor structure of restricted and repetitive behaviors (RRB) in children with autism. Factor extraction procedures of 12 items from the Autism Diagnostic Interview-Revised (ADI-R) were applied in N = 207 individuals with autism. Two interpretable factors were identified: Factor 1--repetitive sensory motor actions and Factor 2--resistance to change. There was a significant negative correlation between an index of level of adaptive functioning and Factor 1. Intraclass correlations were not significant for either factor in a subset of families with two or more siblings with autism (multiplex). No differences in scores were apparent for either factor when multiplex families and families containing only one affected individual with autism (singleton) were compared. RRB in autism are represented by two distinct factors which may reflect two separate groups within autism. Defining subgroups within autism will allow for reduction of clinical heterogeneity and enhance our ability to dissect the genetic etiology of this complex disorder

Analysis of the autism chromosome 2 linkage region: GAD1 and other candidate genes

Autism has a strong and complex genetic component, involving several genes. Genomic screens, including our own, have shown suggestive evidence for linkage over a 20–30 cM region on chromosome 2q31-q33. Two subsequent reports showed that the linkage evidence increased in the subset of families with phrase speech delay (PSD), defined as onset of phrase speech later than 3 years of age. To further investigate the linkage in the presumptive candidate region, microsatellite markers in a 2 cM grid covering the interval from 164 to 203 cM were analyzed in 110 multiplex (2 or more sampled autism patients) families. A maximum heterogeneity LOD (HLOD) score of 1.54 was detected at D2S1776 (173 cM) in the overall dataset (dominant model), increasing to 1.71 in the PSD subset. While not conclusive, these data continue to provide suggestive evidence for linkage, particularly considering replication by multiple independent groups. Positive LOD scores extended over the entire region, continuing to define a broad candidate interval. Association studies were performed on several functional candidates mapping within the region. These included GAD1, encoding GAD67, whose levels are reduced in autopsy brain material from autistic subjects, and STK17B, ABI2, CTLA4, CD28, NEUROD1, PDE1A, HOXD1 and DLX2. We found no evidence for significant allelic association between autism and any of these candidates, suggesting that they do not play a major role in the genetics of autism or that substantial allelic heterogeneity at any one of these loci dilutes potential disease–allele association