This argues for collaborations between emerging and industrialized countries, as exemplified by the long-standing collaboration between our group and an effective Iranian partner, which was instrumental in the elucidating the gene defects responsible for several recessive forms of MR, thereby Selleck KPT-330 paving the way for the diagnosis, prevention

and – eventually – therapy of these disorders. Inhibitors,research,lifescience,medical So far, recessive disorders are considered too rare to justify carrier screening, but this is likely to change as soon as there is a reliable and inexpensive test for all recessive disorders. According to leading manufacturers, “third-generation” sequencing technologies that enable sequencing of the entire human genome for less than 5000 US will be on the market Inhibitors,research,lifescience,medical by the end of 2010 or early in 2011, which indicates that carrier tests for all known recessive disorders will be available sooner rather than later. Indeed, the (US) National Center for Genome Resources has recently teamed up with the Beyond Batten Disease Foundation to develop such a test for approximately 448 single gene defects Inhibitors,research,lifescience,medical using available next-generation sequencing technology. With such

a carrier test at hand, premarital screening can be offered to rule out the possibility that both spouses are heterozygous for Inhibitors,research,lifescience,medical defects in the same gene, and prevention programs can be set up, similar to the successful

prevention of Tay-Sachs disease in Ashkenazim, Inhibitors,research,lifescience,medical which was initiated in the 1970s.40 Whole genome sequencing (WGS) is not only the method of choice for the large-scale elucidation of Mendelian disorders, but it is also a superior alternative for risk factor screening in complex diseases, because it is not fraught with the inherent limitations of GWAS.2,41 There is no doubt that there exist genetic factors which predispose individuals already to disease without sufficing for disease manifestation, as discussed for CNVs that are risk factors for MR, autism, and schizophrenia. Another telling example is a deletion on chromosome 1q that seems to be a necessary but not sufficient prerequisite for thrombocytopenia/absent radius syndrome.42 CNVs predisposing for disease can only be identified efficiently by large case-control studies; attempts to find them by investigating the normal variation, ie, by excluding all CNVs present in healthy individuals, are bound to fail because risk factors for common disorders will be found in the healthy controls, too.