Characterization of genetic and lifestyle factors for determining variation in body mass index, fat mass, percentage of fat mass, and lean mass.

In this study, we simultaneously characterized genetic and lifestyle factors (exercise, smoking, and alcohol consumption) in determining variation in body mass index (BMI), fat mass, percentage of fat mass (PFM), and lean mass while adjusting for the effects of age and sex. Six hundred fifty-eight Caucasian individuals from 48 pedigrees were studied for BMI. Among these individuals, 289 from 38 pedigrees were studied for fat mass, PFM, and lean mass measured by dual X-ray absorptiometry (DXA). After adjusting for age, sex, and lifestyle factors, the heritabilities (h(2)) of BMI, fat mass, PFM, and lean mass ranged from 0.52 to 0.57 with associated standard errors ranging from 0.09 to 0.14. After accounting for significant sex and age effects, exercise had significant effects for all the phenotypes studied, and the effects of smoking and alcohol consumption were not significant. Therefore, significant proportions of variation in BMI, fat mass, PFM, and lean mass were under genetic control, and exercise had a significant effect in reducing BMI, fat mass, and PFM and in increasing lean mass. This study warrants further genetic linkage analyses to search for genes for the obesity-related phenotypes measured by DXA in our population.

Toward high-throughput genotyping: dynamic and automatic software for manipulating large-scale genotype data using fluorescently labeled dinucleotide markers.

To efficiently manipulate large amounts of genotype data generated with fluorescently labeled dinucleotide markers, we developed a Microsoft database management system, named. offers several advantages. First, it accommodates the dynamic nature of the accumulations of genotype data during the genotyping process; some data need to be confirmed or replaced by repeat lab procedures. By using, the raw genotype data can be imported easily and continuously and incorporated into the database during the genotyping process that may continue over an extended period of time in large projects. Second, almost all of the procedures are automatic, including autocomparison of the raw data read by different technicians from the same gel, autoadjustment among the allele fragment-size data from cross-runs or cross-platforms, autobinning of alleles, and autocompilation of genotype data for suitable programs to perform inheritance check in pedigrees. Third, provides functions to track electrophoresis gel files to locate gel or sample sources for any resultant genotype data, which is extremely helpful for double-checking consistency of raw and final data and for directing repeat experiments. In addition, the user-friendly graphic interface of renders processing of large amounts of data much less labor-intensive. Furthermore, has built-in mechanisms to detect some genotyping errors and to assess the quality of genotype data that then are summarized in the statistic reports automatically generated by. The can easily handle >500,000 genotype data entries, a number more than sufficient for typical whole-genome linkage studies. The modules and programs we developed for the can be extended to other database platforms, such as Microsoft SQL server, if the capability to handle still greater quantities of genotype data simultaneously is desired.

Differential actions of neurotrophins on apoptosis mediated by the low affinity neurotrophin receptor p75NTR in immortalised neuronal cell lines.

The low affinity neurotrophin receptor (p75NTR) mediates apoptosis of a number of neuronal and non-neuronal cells but the signals leading to the apoptosis remain obscure. To reveal the mechanism of p75NTR-mediated apoptosis, a neural cell line expressing human p75NTR was established. The human cDNA fragment encoding for p75NTR was PCR-amplified, cloned into the retrovirus expression vector pXT-1 and transfected into the rat cerebellum cell line R2. The expression of p75NTR in the R2 cell line was demonstrated by both Northern blotting analysis and immunocytochemistry. Serum withdrawal induced dramatic apoptosis in p75NTR-expressing R2 cells (R2L1) but not in pXT-1 transfected control R2 cells (R2P). Reverse transcription polymerase chain reaction (RT-PCR) revealed that these cell lines express trkA and trkB but not trkC. The apoptosis of R2L1 cells triggered by the serum deprivation for 48 h was completely prevented by neurotrophin-3 and the antibody to p75NTR but only partially prevented by the nerve growth factor and brain derived neurotrophic factor. We conclude that the p75NTR mediates apoptosis of R2L1 cells by its intrinsic receptor effects requiring an unbound status of this receptor and that the apoptosis is prevented by neurotrophins or the antibody to p75NTR through distinct mechanisms.