ProtocadherinX/Y, a Candidate Gene-Pair for Schizophrenia and Schizoaffective Disorder: A DHPLC Investigation of Gonomic Sequence

Protocadherin X and Protocadherin Y (PCDHX and PCDHY) are cell-surface adhesion molecules expressed predominantly in the brain. The PCDHX/Y gene-pair was generated by an X-Y translocation approximately 3 million years ago (MYA) that gave rise to the Homo sapiens-specific region of Xq21.3 and Yp11.2 homology. Genes within this region are expected to code for sexually dimorphic human characteristics, including, for example, cerebral asymmetry a dimension of variation that has been suggested is relevant to psychosis. We examined differences in patients with schizophrenic or schizoaffective psychosis in the genomic sequence of PCDHX and PCDHY in coding and adjacent intronic sequences using denaturing high performance liquid chromatography (DHPLC). Three coding variants were detected in PCDHX and two in PCDHY. However, neither the coding variants nor the intronic polymorphisms could be related to psychosis within families. Low sequence variation suggests selective pressure against sequence change in modern humans in contrast to the structural chromosomal and sequence changes including fixed X-Y differences that occurred in this region earlier in hominid evolution. Our findings exclude sequence variation in PCDHX/Y as relevant to the aetiology of psychosis. However, we note the unusual status of this region with respect to X-inactivation. Further investigation of the epigenetic control of PCDHX/Y in relation to psychosis is warran

Size of hippocampal pyramidal neurons in schizophrenia

Background Meta-analyses of hippocampal size have indicated thatthis structure is smaller in schizophrenia.This could reflect a reductioninthe size of constituent neurons or a reduced number of neurons. Aims To measure the size of hippocampalpyramidalneuronsinthe hippocampalpyramidalneurons inthe brains of peoplewith andwithout schizophrenia. Method Pyramidalneuron size in hippocampal subfieldswas estimated stereologically fromsections taken at 5mmintervals throughoutthewhole length of right and left hippocampi from andleft the brains of13 peoplewith schizophrenia and16 controls.Resultswere assessed using repeated-measures analysis of covariance looking for amain effectof diagnosis and gender, andinteractions of and interactions thesewith side. Results Wewere unable to detect significantdifferences related to diagnosis, gender or side for any hippocampal subfield for this series of cases. Conclusions For this series of brains, hippocampal cell size is unchangedin schizophrenia

Factor structure and familiality of first-rank symptoms in sibling pairs with schizophrenia and schizoaffective disorder

Background Since their introduction as diagnostic criteria by Schneider in 1937, nuclear symptoms have played a key role in concepts of schizophrenia, but their relationship to each other and to genetic predisposition has been unclear. Aims To ascertain the factor structure and familiality of nuclear symptoms. Methods Nuclear (Schneiderian) symptoms were extracted from case notes and interviews in a study of 103 sibling pairs with DSM-III-R schizophrenia or schizoaffective disorder. Results Principal components analysis demonstrated two major factors : one, accounting for about 50% of the variance, groups thought withdrawal, insertion and broadcasting, with delusions of control ; and the second, accounting for <20% of the variance, groups together third-person voices, thought echo and running commentary. Factor I was significantly correlated within sibling pairs. Conclusions The correlation within sibling pairs suggests that, contrary to the conclusion of some previous studies, some nuclear symptoms do show a degree of familiality and therefore perhaps heritability

Body image, body dissatisfaction and weight status in south asian children: a cross-sectional study

Background Childhood obesity is a continuing problem in the UK and South Asian children represent a group that are particularly vulnerable to its health consequences. The relationship between body dissatisfaction and obesity is well documented in older children and adults, but is less clear in young children, particularly South Asians. A better understanding of this relationship in young South Asian children will inform the design and delivery of obesity intervention programmes. The aim of this study is to describe body image size perception and dissatisfaction, and their relationship to weight status in primary school aged UK South Asian children. Methods Objective measures of height and weight were undertaken on 574 predominantly South Asian children aged 5-7 (296 boys and 278 girls). BMI z-scores, and weight status (underweight, healthy weight, overweight or obese) were calculated based on the UK 1990 BMI reference charts. Figure rating scales were used to assess perceived body image size (asking children to identify their perceived body size) and dissatisfaction (difference between perceived current and ideal body size). The relationship between these and weight status were examined using multivariate analyses. Results Perceived body image size was positively associated with weight status (partial regression coefficient for overweight/obese vs. non-overweight/obese was 0.63 (95% CI 0.26-0.99) and for BMI z-score was 0.21 (95% CI 0.10-0.31), adjusted for sex, age and ethnicity). Body dissatisfaction was also associated with weight status, with overweight and obese children more likely to select thinner ideal body size than healthy weight children (adjusted partial regression coefficient for overweight/obese vs. non-overweight/obese was 1.47 (95% CI 0.99-1.96) and for BMI z-score was 0.54 (95% CI 0.40-0.67)). Conclusions Awareness of body image size and increasing body dissatisfaction with higher weight status is established at a young age in this population. This needs to be considered when designing interventions to reduce obesity in young children, in terms of both benefits and harms

Analysis of genetic systems using experimental evolution and whole-genome sequencing

The application of whole-genome sequencing to the study of microbial evolution promises to reveal the complex functional networks of mutations that underlie adaptation. A recent study of parallel evolution in populations of Escherichia coli shows how adaptation involves both functional changes to specific proteins as well as global changes in regulation

Mutation Accumulation in a Selfing Population: Consequences of Different Mutation Rates between Selfers and Outcrossers

Currently existing theories predict that because deleterious mutations accumulate at a higher rate, selfing populations suffer from more intense genetic degradation relative to outcrossing populations. This prediction may not always be true when we consider a potential difference in deleterious mutation rate between selfers and outcrossers. By analyzing the evolutionary stability of selfing and outcrossing in an infinite population, we found that the genome-wide deleterious mutation rate would be lower in selfing than in outcrossing organisms. When this difference in mutation rate was included in simulations, we found that in a small population, mutations accumulated more slowly under selfing rather than outcrossing. This result suggests that under frequent and intense bottlenecks, a selfing population may have a lower risk of genetic extinction than an outcrossing population

Subtelomeric study of 132 patients with mental retardation reveals 9 chromosomal anomalies and contributes to the delineation of submicroscopic deletions of 1pter, 2qter, 4pter, 5qter and 9qter

BACKGROUND: Cryptic chromosome imbalances are increasingly acknowledged as a cause for mental retardation and learning disability. New phenotypes associated with specific rearrangements are also being recognized. Techniques for screening for subtelomeric rearrangements are commercially available, allowing the implementation in a diagnostic service laboratory. We report the diagnostic yield in a series of 132 subjects with mental retardation, and the associated clinical phenotypes. METHODS: We applied commercially available subtelomeric fluorescence in situ hybridization (FISH). All patients referred for subtelomeric screening in a 5-year period were reviewed and abnormal cases were further characterized clinically and if possible molecularly. RESULTS: We identified nine chromosomal rearrangements (two of which were in sisters) corresponding to a diagnostic yield of approx. 7%. All had dysmorphic features. Five had imbalances leading to recognizable phenotypes. CONCLUSION: Subtelomeric screening is a useful adjunct to conventional cytogenetic analyses, and should be considered in mentally retarded subjects with dysmorphic features and unknown cause