The latest news from the GENOMOS study

Most common age-related diseases such as osteoporosis, have strong genetic influences and therefore intense efforts are ongoing to identify the underlying genetic variants. Knowledge of these variants can help in understanding the disease process and might benefit development of interventions and diagnostics. Association studies have now become the standard approach to uncover the genetic effects of common variants. Yet, in all fields of complex disease genetics - including osteoporosis - progress in identifying these genetic factors has been hampered by often controversial results. Because of the complicated genetic architecture of the diseases and the small effect size for each individual risk alleles, this is mostly due to low statistical power and limitations of analytical methods. It is now recognised that association analysis followed by replication and prospective multi-centred meta-analysis is currently the best way forward to identify genetic markers for complex traits, such as osteoporosis. To accomplish this, large (global) collaborative consortia have been established that have large collections of DNA samples from subjects with a certain phenotype and that use standardized methodology and definitions, to quantify by meta-analysis the subtle effects of the responsible gene variants. The GENOMOS consortium has played such a role in the field of osteoporosis and has initially identified and refuted associations of well known candidate genes. This consortium is now expected to play an important role in validation of risk alleles coming from Genome Wide Association Studies (GWAS) for osteoporosis, some of which have just been published. Together with genetic studies on more rare syndromes, the GWA approach in combination with the GENOMOS consortium, is likely to help in clarifying the genetic architecture of complex bone traits such as BMD, and - eventually - in understanding the genetics of clinically relevant endpoints in osteoporosis, i.e., fracture risk. Such genetic insights will be useful in understanding biology and are likely to also find applications in clinical practice.</p

The Caenorhabditis eleguns genome contains monomorphic minisatellites and simple sequences

Many species have been shown to contain tandemly repeated short sequence DNA kinown as minisatellites and simple sequence motifs. Due to allelic variation in the copy number of the repeat unit these loci are usually highly polymorphic. Here we demonstrate the presence of sequences in the genome of the nematode Caenorhabditis elegans which are homologous to two sets of short sequence DNA. However, when two independent strains were compared no polymorphism for these sequences could be detected.</p

Genetic Vitamin D Receptor Polymorphisms and Risk of Disease

[...] Below, we present a more detailed description of the genomic organization of the VDR gene, including discussion on polymorphisms, linkage disequilibrium, and haplotypes. We then describe association studies of VDR polymorphisms in relation to different diseases. Historically speaking, studies of VDR polymorphisms in relation to bone endpoints, including osteoporosis in particular, have received most attention while the analysis of VDR polymorphisms in relation to other diseases, including breast and prostate cancer and immune-related disorders, has reached the literature somewhat later on. This allows studies on associations with bone endpoints to be compared to a certain extent and to illustrate some of the difficulties in interpreting the results. [...

Identity and Paternity Testing of Cattle:Application of a Deoxyribonucleic Acid Profiling Protocol

We have applied DNA profiling for identity and parentage studies of cattle using a standardized procedure based on synthetic micro- and minisatellite multilocus core probes in Southern blot hybridization assays. This protocol is useful for paternity analysis of cattle and for real case work (e.g., identity and paternity disputes).</p

Genetics and biology of vitamin D receptor polymorphisms

The vitamin D endocrine system is involved in a wide variety of biological processes including bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation. Variations in this endocrine system have, thus, been linked to several common diseases, including osteoarthritis (OA), diabetes, cancer, cardiovascular disease, and tuberculosis. Evidence to support this pleiotropic character of vitamin D has included epidemiological studies on circulating vitamin D hormone levels, but also genetic epidemiological studies. Genetic studies provide excellent opportunities to link molecular insights with epidemiological data and have therefore gained much interest. DNA sequence variations, which occur frequently i