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    Approaches to identifying genes involved in osteoporosis

    There are techniques that scientists can use to identify and further investigate genes that may play a role in osteoporosis. One of these methods is association studies that identify polymorphisms in candidate genes in a population based studies. That is to say that genes alleles are identified in populations that have a decrease in bone mineral density or have an increased risk of suffering osteoporosis fractures. the advantage of association studies is that they are fairly easy to perform, however results may not always be truly accurate due to the often small sizes of populations available in which to carry out the genetic work.

    The use of linkage analysis in identifying genes involved in osteoporosis

    Another technique used to identify genes that may play a role in osteoporosis is that of linkage analysis; this can be performed in both humans and on animals. Linkage studies have identified many genes that are involved in rare bone diseases that may have osteoporosis as a side effect. Linkage studies have also enabled the identification of chromosomal areas that contain genes that are involved in bone loss maintenance. The development of dense SNP maps has led to a great increase in the success rates of genetic linkage studies. One of the drawbacks of linkage studies when investigating genes that may be involved in osteoporosis is that it is very difficult to identify genes that only play a moderate role in bone mass regulation. Mice are often used to investigate genes that are involved in osteoporosis. In this approach normal mice are crossed with mice that are known to have either low or high bone mineral densities. The genes are then tried to be mapped in the F2 population where recessive alleles can be identified. The advantage of this sort of study is that the environment can be controlled, thus limiting external factors that may impact bone mass regulation. Microarray studies are also carried out in order to identify genes that may be differently regulated in mice that have low or high bone density in comparisons to controls. One of the genes (Alox15) identified by a microarray approach in mice has been found to have a homolog in humans (Alox12), that is also able to regulate bone mineral density.

    References
    Altmuller et al, 2001. Genomewide scans of complex human diseases: True linkage is hard to find. Am. J. Med. Genet. 69: 936-950
    Klein et al, 2004. regulation of bone mass in mice by the lipoxygenase gene Alox15. Science 303:229-232
    Ichikawa et al, 2006. Human Alox12, but not Alox15, is associated with BMD in white men and women. J. Bone Miner Res. 21: 556-564
    Ralston and Crombrrugghe, 2006. Genetic Regulation of Bone Mass and Susceptibility to Osteoporosis.Genes and development. 20;2492-2506