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Thanks to for the link.
Today, 3/21, is World Down Syndrome Day. Also known as Trisomy 21, because it involves three copies of chromosome 21 instead of the usual two (see image), Down syndrome is the most complex of genetic disorders that is compatible with survival (other trisomies are more common, but are lethal). Even Down syndrome is associated with ~50% lethality of embryos. In the US, 1 in 691 babies is born with Down syndrome.
Too much of a good thing: Anywhere from 300 to 500 genes have altered levels and function, resulting 80 or 90 possible symptoms and an instantly recognizable phenotype (physical appearance). For example, patients have a 1 in 5 chance of developing a hole in the heart, compared to an incidence of 1:10,000 in the normal population. Down syndrome is extraordinarily complex, and my friend and colleague Roger Reeves has dedicated his career to helping patients with his research.
Cerebellar size: Dr. Reeves showed that the reduced size of the cerebellum in patients was due to defects in the sonic hedgehog signaling pathway. Using a drug that activated this pathway, he was able to restore the number of cerebellar cells to normalcy in a mouse model of Down syndrome, pointing to a therapeutic potential for the central nervous system deficits in patients.
Tweaking circuits: In the hippocampus—that part of the brain that’s used to navigate landmarks and fix memories, Down syndrome patients show an excess of inhibitory pathways compared to excitatory ones. A drug that is already FDA-approved works wonders on mice with the equivalent of Down syndrome, restoring balance to their brain. This drug is now in clinical trials for Down syndrome patients.
It's not all bad: Research on Down syndrome has broad impact. For example, having three copies of a tumor suppressor gene means that patients have a 93% lower incidence of developing certain cancers. This insight could help treat cancers in the general population. Plus, as Roger likes to say, if you know anyone with Down syndrome, they tend to be pretty interesting individuals in their own right.
For more on Roger's research: http://goo.gl/uSJWm
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