No abstract

Our study indicates that individuals with TI deletion generally have more behavioral and psychological problems than individuals with the TII deletion or UPD. Four recently identified genes have been identified in the chromosome region between BP1 and BP2 with 1 of the genes (NIPA-1) expressed in mouse brain tissue but not thought to be imprinted. It may be important for brain development or function. These genes are deleted in individuals with TI deletion and are implicated in compulsive behavior and lower intellectual ability in individuals with TI versus TII.

No abstract

Scientific Abstract To assess the feasibility and relevance of using lymphoblastoid cell lines to study the role of noncoding RNAs in the etiology of autism, we evaluated global expression profiling of 470 mature human microRNAs from 6 subjects with autism compared with 6 matched controls. Differential expression (either higher or lower) for 9 of the 470 microRNAs was observed in our autism samples compared with controls. Potential target genes for these microRNAs were identified using computer tools which included several autism susceptibility genes. Our preliminary results indicate microRNAs should be considered and evaluated in the etiology of autism. In addition, analysis of this class of noncoding RNAs in lymphoblastoid cells has the potential to reveal at least a subset of brain-related microRNAs implicated in autism. Subsequently, this model system should allow for detection of complex subtle changes in susceptibility genes/pathways contributing to autism.

Prader-Willi syndrome (PWS), the most common genetic cause of marked obesity in humans, is usually due to a de novo paternally derived chromosome 15q11-q13 deletion or maternal disomy 15 [(uniparental disomy (UPD)]. Obesity is due to energy imbalance, but few studies have examined fat patterning and obesity-related factors in subjects with PWS (deletions and UPD) compared with subjects with simple obesity. We examined for differences in fatness patterning and lipid, leptin, and glucose and insulin levels in subjects with simple obesity and PWS and adjusted for gender, age, and body mass index (BMI). Fasting peripheral blood samples and cross-sectional magnetic resonance image scans at the level of the umbilicus were obtained in 55 subjects ranging in age from 10.4 to 49 years: 20 PWS deletion, 17 PWS UPD, and 18 obese controls. Subcutaneous fat area (SFA) and intra-abdominal visceral fat area (VFA) were calculated. No significant difference was seen between the PWS deletion subjects or PWS UPD subjects for fatness measurements or leptin levels. Twenty-three of 37 PWS subjects met the criteria for obesity (BMI > 95th percentile). No significant differences were observed for SFA and VFA between the PWS subjects judged to be obese and control subjects with simple obesity. There was an overall trend for decreased VFA in the PWS subjects but not significantly different. VFA was significantly positively correlated with both fasting insulin and total cholesterol in PWS deletion subjects but not in PWS UPD subjects or obese controls. Fasting insulin level was significantly lower in the obese PWS subjects compared with subjects with simple obesity, and insulin sensitivity (QUICKI) was significantly higher in PWS subjects with obesity. Homeostasis model assessment (HOMA) and QUICKI values were correlated and in opposite directions with triglycerides in the obese PWS subjects but not in the obese controls. Subjects in each group were stratified according to published criteria on the basis of their level of visceral fat (e.g. > or = 130 cm(2)) to assess the influence of VFA on metabolic abnormalities. In the obese PWS subjects, the fasting triglyceride, glucose, and insulin levels, and HOMA value were significantly elevated, while the QUICKI value was significantly lower in those with VFA > or = 130 cm(2). Such significant differences were not seen in the obese control group. Our results indicate that VFA may be regulated differently in PWS subjects compared to individuals with simple obesity. Insulin resistance is lower in PWS subjects and insulin sensitivity is higher compared with obese controls. PWS subjects with increased VFA may be at a higher risk of obesity-related complications compared to PWS subjects without increased VFA.

Background-X-chromosome inactivation (XCI) is the mechanism by which gene dosage uniformity is achieved between female mammals with two X chromosomes and male mammals with a single X chromosome, and is thought to occur randomly. For molecular genetic testing, accessible tissues (eg blood) are commonly studied, but the relationship with inaccessible tissues (eg brain) is poorly understood. For accessible tissues to be informative for genetic analysis, a high degree of concordance of genetic findings among tissue types is required.

Research Methods and Procedures: Seventy-two individuals (27 PWS deletion, 21 PWS uniparental disomy, and 24 obese controls) 10 to 49 years old were studied with the use of DXA. Body composition measures were obtained, and regional fat and lean mass patterns were characterized. Significant differences were assessed with Student's t test and ANOVA adjusting for age, gender, and BMI. Results: Significant differences between the PWS and obese groups were found for lean measures of the arms, legs, and trunk. Total lean mass was significantly lower in PWS than in obese subjects for arms, trunk, and especially legs. Furthermore, two body regions (legs and trunk) showed significant differences for fat and lean measures between PWS and obese males. However, significant differences between PWS and obese females for these measures were found only for the legs. No significant differences were identified between PWS deletion and uniparental disomy subjects. Discussion: Our results demonstrate that PWS individuals do, in fact, have an unusual body composition and fatness patterns, characterized by reduced lean tissue and increased adiposity, with PWS males contributing most with fat patterns more similar to females.

Among thousands of non-protein-coding RNAs which have been found in humans, a significant group represents snoRNA molecules that guide other types of RNAs to specific chemical modifications, cleavages, or proper folding. Yet, hundreds of mammalian snoRNAs have unknown function and are referred to as "orphan" molecules. In 2006, for the first time, it was shown that a particular orphan snoRNA (HBII-52) plays an important role in the regulation of alternative splicing of the serotonin receptor gene in humans and other mammals. In order to facilitate the investigation of possible involvement of snoRNAs in the regulation of pre-mRNA processing, we developed a new computational web resource, snoTARGET, which searches for possible guiding sites for snoRNAs among the entire set of human and rodent exonic and intronic sequences. Application of snoTARGET for finding possible guiding sites for a number of human and rodent orphan C/D-box snoRNAs showed that another subgroup of these molecules (HBII-85) have statistically elevated guiding preferences toward exons compared to introns. Moreover, these energetically favorable putative targets of HBII-85 snoRNAs are non-randomly associated with genes producing alternatively spliced mRNA isoforms. The snoTARGET resource is freely available at: (http://hsc.utoledo.edu/depts/bioinfo/snotarget.html).