under the auspices of the National Center for Biotechnology. One example is GenBank, which is a National Institutes of Health (NIH) database of publicly available DNA sequences that have been submitted by individual laboratories or from large-scale sequencing projects (Benson et al., 2008). A significant incentive for such submissions is the requirement by scientific journals for deposition to GenBank or a similar database so that an accession number will be included in a published article.

Also, a significant response to institutional, individual, and other barriers to information access has been the requirement by NIH that applicants for grants that exceed $500,000 include a plan for “timely release and sharing of final research data from NIH-supported studies” (NIH, 2003, unpaged). In addition, some private organizations such as the Myelin Repair Foundation have grant provisions to speed information sharing (MRF, 2010; see also Schofield et al., 2009). More examples of initiatives to increase access to information and other infrastructure resources are described below and in Chapter 5.

Animal Models

Development of disease models in animals yields major opportunities for discovery of the genetic and biochemical basis for rare diseases, the identification of therapeutic targets, and the testing of new drugs and biologics for efficacy and safety. A number of genetic diseases occur naturally in animals (e.g., hemophilia B in dogs [Kay et al., 1994]), and various techniques exist for creating such models when they do not exist in nature. Mouse models are common, but simpler, more rapidly reproducing models such as the zebrafish are also valuable where genetic mouse models do not fully recreate human disease. Technological advances have allowed the development of long-sought alternative animal models for Huntington disease (monkey) and cystic fibrosis (pig) (Wolfe, 2009), but satisfactory animal models still await many rare diseases, for example, Smith Lemli Opitz syndrome (Merkens et al., 2009).

Mouse models, and occasionally other animal models, can be created using both forward and reverse genetic manipulation. Forward genetics involves the altering of specific genes to change their expression patterns and products. Although expensive and time-consuming, this approach is now a fundamental experimental strategy and has been an important contributor to research advances for an array of rare diseases. Reverse genetics is carried out by exposing animals to mutagenic agents and identifying genetic disorders by careful genotyping and phenotyping of the animals. Using this approach, a lethal skeletal dysplasia was created in mice that led to the identification of a deficiency of the GMAP-210 gene in these mice as well as in human achondrogenesis type 1A (Smits et al., 2010). The ability



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