On the road to developing treatments for the chromosome 18 conditions, identification of key genes is a major milestone. Key genes are the handful of genes on chromosome 18 that, when deleted or duplicated, lead to medical and educational differences. Over the last several years, multiple studies have published data that has been helpful in narrowing the search for key genes. Surprisingly, these data have helped us by showing which genes are NOT likely to have an effect when deleted. Much of this data was obtained by studying knockout mice. These are mice that have a single gene that has been "knocked out". This allows us to see what happens when that gene is missing. While data from mice is helpful, data from people is the most informative. Interestingly, this can happen naturally, although it is rare.
Four different manuscripts published over the last couple of years have involved the genetic analysis of tens of thousands of healthy individuals. These data revealed that some healthy individuals have deletions of both copies of certain genes. As it turns out, there are in fact hundreds of genes that can be
completely absent without causing ill effects. Looking at the data from thousands of people, there are clearly some genes that we can do without. Thirty five of these genes are on chromosome 18. This means that, of the 263 genes on chromosome 18, 35 of them can have both copies deleted without causing any problems. Therefore, we think it is safe to conclude that having one of the two copies deleted would not cause a problem either, and we can cross these genes off our list of potential key genes. All in all, we currently think that 198 (75%) of the genes on chromosome are not key genes. Thanks to these "knockout people", we have significantly reduced the number of possible key genes, allowing us to narrow our focus to the remaining 65 genes.
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