1. Chapman NH, Estes A, Munson J, Bernier R, Webb SJ, Rothstein JH, Minshew NJ, Dawson G, Schellenberg GD, Wijsman EM. {{Genome-scan for IQ discrepancy in autism: evidence for loci on chromosomes 10 and 16}}. {Hum Genet} (Oct 21)
2. Johnson SB, Whitney G, McAuliffe M, Wang H, McCreedy E, Rozenblit L, Evans CC. {{Using global unique identifiers to link autism collections}}. {J Am Med Inform Assoc} (Nov 1);17(6):689-695.
Objective To propose a centralized method for generating global unique identifiers to link collections of research data and specimens. Design The work is a collaboration between the Simons Foundation Autism Research Initiative and the National Database for Autism Research. The system is implemented as a web service: an investigator inputs identifying information about a participant into a client application and sends encrypted information to a server application, which returns a generated global unique identifier. The authors evaluated the system using a volume test of one million simulated individuals and a field test on 2000 families (over 8000 individual participants) in an autism study. Measurements Inverse probability of hash codes; rate of false identity of two individuals; rate of false split of single individual; percentage of subjects for which identifying information could be collected; percentage of hash codes generated successfully. Results Large-volume simulation generated no false splits or false identity. Field testing in the Simons Foundation Autism Research Initiative Simplex Collection produced identifiers for 96% of children in the study and 77% of parents. On average, four out of five hash codes per subject were generated perfectly (only one perfect hash is required for subsequent matching). Discussion The system must achieve balance among the competing goals of distinguishing individuals, collecting accurate information for matching, and protecting confidentiality. Considerable effort is required to obtain approval from institutional review boards, obtain consent from participants, and to achieve compliance from sites during a multicenter study. Conclusion Generic unique identifiers have the potential to link collections of research data, augment the amount and types of data available for individuals, support detection of overlap between collections, and facilitate replication of research findings.
3. Sajdel-Sulkowska EM, Xu M, McGinnis W, Koibuchi N. {{Brain Region-Specific Changes in Oxidative Stress and Neurotrophin Levels in Autism Spectrum Disorders (ASD)}}. {Cerebellum} (Oct 22)
Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by social and language deficits, stereotypic behavior, and abnormalities in motor functions. The particular set of behavioral impairments expressed in any given individual is variable across the spectrum. These behavioral abnormalities are consistent with our current understanding of the neuropathology of ASD which suggests abnormalities in the amygdala, temporal and frontal cortexes, hippocampus, and cerebellum. However, regions unrelated to these behavioral deficits appear largely intact. Both genetic predisposition and environmental toxins and toxicants have been implicated in the etiology of autism; the impact of these environmental triggers is associated with increases in oxidative stress, and is further exacerbated when combined with genetic susceptibility. We have previously reported increased levels of 3-nitrotyrosine (3-NT), a marker of oxidative stress, in ASD cerebella. We have also shown that this increase was associated with an elevation in neurotrophin-3 (NT-3) levels. The objectives of the current study were to determine whether the increase in oxidative stress in ASD is brain region-specific, to identify the specific brain regions affected by oxidative stress, and to compare brain region-specific NT-3 expression between ASD and control cases. The levels of 3-NT and NT-3 were measured with specific ELISAs in individual brain regions of two autistic and age- and postmortem interval (PMI)–matched control donors. In the control brain, the levels of 3-NT were uniformly low in all brain regions examined ranging from 1.6 to 12.0 pmol/g. On the other hand, there was a great variation in 3-NT levels between individual brain regions of the autistic brains ranging from 1.7 to 281.2 pmol/g. The particular brain regions with the increased 3-NT and the magnitude of the increase were both different in the two autistic cases. In the older autistic case, the brain regions with highest levels of 3-NT included the orbitofrontal cortex (214.5 pmol/g), Wernicke’s area (171.7 pmol/g), cerebellar vermis (81.2 pmol/g), cerebellar hemisphere (37.2 pmol/g), and pons (13.6 pmol/g); these brain areas are associated with the speech processing, sensory and motor coordination, emotional and social behavior, and memory. Brain regions that showed 3-NT increase in both autistic cases included the cerebellar hemispheres and putamen. Consistent with our earlier report, we found an increase in NT-3 levels in the cerebellar hemisphere in both autistic cases. We also detected an increase in NT-3 level in the dorsolateral prefrontal cortex (BA46) in the older autistic case and in the Wernicke’s area and cingulate gyrus in the younger case. These preliminary results reveal, for the first time, brain region-specific changes in oxidative stress marker 3-NT and neurotrophin-3 levels in ASD.
