Over the past years substantial progress has been made in the molecular elucidation of monogenic forms of obesity both in rodents and in humans. In addition, several quantitive trait loci have been mapped in mice. In humans, non-parametric linkage studies have led to the identification of relevant chromosomal regions, some of which have already been confirmed. In this review we focus on an interpretation of the heritability estimates obtained in twin, family and adoption studies. These estimates include both direct and indirect genetic effects. Non-additive genetic factors seemingly contribute even more than additive factors. The importance of the non-shared environment is stressed. GeneÂgene interactions need to be considered when interpreting recent molecular genetic results pertaining to haplo-insufficiency mutations in the melanocortin-4 receptor gene. We conclude by discussing the implications of the recent molecular findings in humans for phenotypical assessment in ongoing family studies.

The 825-C/T polymorphism of the beta 3 subunit of the heterotrimeric G protein gene (GNB3) has been shown to be associated with essential hypertension in humans. Recently, it was also reported that the 825-T allele has a higher frequency in obese than non-obese hypertensives suggesting that the primary effect of this allele is on body weight. The association to hypertension might merely be a secondary effect of the higher weight of the respective allele carriers. To investigate an involvement of the 825-T allele in body weight regulation in young individuals, we evaluated allele frequencies in 440 extremely obese children and adolescents (82.9% had a body mass index [BMI] > or = 99th percentile), 51 obese students (BMI > or = 90th percentile), 110 normal weight students (BMI between 40th and 60th percentile) and 144 underweight students (BMI < or = 15th percentile). The study groups were genotyped by polymerase chain reaction with subsequent restriction fragment length polymorphism analysis (PCR-RFLP). The one-sided Yates-corrected chi(2)-test and the Cochran-Armitage trend test for association were performed. Tests for association were negative. The 825-T allele frequencies were similar in the four study groups belonging to different weight ranges (extreme early onset obesity: 0.29; obesity: 0.28; normal weight: 0.35; underweight: 0.32). Similarly, genotype frequencies did not differ between the groups. We concluded that the 825-T allele of the GNB3 does not play a major role in weight regulation in German children, adolescents and young adults.

The mean pre-post changes found in all parameters investigated consistently correspond with benefits desired from medication with MPH in children with HD. Absolute differences in microevents and variability seem to depend on the daily dose of MPH after adjustment for BMI.

a Although formalin fixed paraffin preserved (FFPP) tissues are a major resource for retrospective studies of disease progression, their use in vibrational spectroscopy studies has been undermined by issues of contributions of substrate and paraffin wax which persist in the spectra and can compromise spectral analysis. Recognising the microcrystalline nature of the wax in the tissue, which are inhomogeneously oriented with respect to the polarisation of the Raman source laser, in this study, we have developed a novel method for removing the paraffin wax contributions to the spectra using matrices of multiple wax spectra. FFPP tissue sections from the oral mucosca were obtained and, with no further chemical processing, the Raman spectral analysis of two regions, epithelium and connective tissue were compared. Matrices of multiple wax spectra were collected from different regions and subtracted from the epithelial and connective tissue spectra using a least squares analysis with non-negative constraints. Spectra of multiple cell components such as DNA and RNA were used in fitting the least squares model to reduce the residual error. The use of a data matrix of multiple wax spectra, as opposed to a single spectrum, results in a more accurate removal of the wax, hence reducing its contribution to spectral analysis. In unprocessed FFPP tissue sections, the contribution of the glass substrate is seen to be minimised in comparison to chemically dewaxed FFPP tissue sections. Contributions of the glass substrate were also successfully removed digitally using the same methodology. The combined results indicate that direct analysis of FFPP tissue sections is feasible using Raman spectroscopy, avoiding the need for chemical dewaxing. Additionally, the ability to use glass slides is very important in translation to the clinic.

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