The Antarctic icefish (Chaenocephalus aceratus) provides several evolutionary models of human disease, including osteopenia, lipid storage diseases, and anemia. For osteopenia, a reduction in bone mineral density, identifying genetic factors in icefish that underlie the loss of bone mineral density in icefish over evolutionary time can lead to a better understanding of the mechanisms that lead to bone loss over developmental time in aging humans.Antarctic icefish have greatly reduced skeletal mineralization. Skeletal reduction in icefish occurs by at least two mechanisms. The first is by delaying activation of bone mineralization genes, such as co/7a7. This results in a skeleton that is largely cartilaginous. Regulatory genes that control the timing of bone mineralization in icefish are as yet unknown. The second mechanism of icefish skeletal reduction is a decrease in the extent of mineralization in the skeletal elements that do ossify. Little is yet known about factors that control this process. Molecular genetic comparison of icefish to closely related robustly skeletonized fish, such as the rockcod {Notothenia coriiceps), will help identify regulatory factors essential for the maintenance of bone mineral density. Antarctic icefish accumulate lipids in muscle, skeleton, and connective tissue. This phenotype resembles human disease states such as Chanarin-Dorfman syndrome and neutral lipid storage disease with myopathy. Icefish muscle cells are riddled with lipid vesicles but few studies have investigated the molecular genetic mechanisms that cause icefish to accumulate lipid deposits. In humans, such deposits are debilitating, but in icefish, they are favored by natural selection because they make the body less dense, thus facilitating prey capture off the ocean floor. Icefish have lost the ability to form red blood cells resulting in profound anemia. The cost of this disaptation is low due to the high capacity of cold water to dissolve oxygen and adaptive compensatory responses, including changes in the circulatory system that involve low blood viscosity, large bore capillaries, increased vascularity, cardiomegaly, and high blood flow with low pressure. In addition, icefish hemoglobin genes have become pseudo genes. This situation thus provides an opportunity to identify hematopoietic regulatory factors present in rockcod, the "wild-type control" but absent from icefish, the "evolutionary mutant". Such genes become candidates for genes involved in human anemias. A group in Korea is sequencing Notothenia coriiceps, a fish closely related to icefish that possesses a heavily mineralized skeleton, does not accumulate lipids in muscle and bone, and has a high hematocrit. Thus, a comparator genome sequence with the "healthy" phenotype will be available, making the sequencing of the icefish (C. aceratus), our disease model, even more valuable.