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One of the first protein polymorphisms identified in humans involves alternative forms of haptoglobin, one of the most abundant proteins in the blood. The genetic origins and medical significance of this variation have puzzled scientists since its discovery. Now, a team of researchers from the Ó³»­´«Ã½â€™s Medical and Population Genetics Program led by institute member Steve McCarroll and postdoctoral associate Linda Boettger has revealed that haptoglobin variation likely arose from the combined effects of many deletions among human ancestors. , published this week in Nature Genetics, goes on to find that these deletions contribute to lower blood cholesterol levels. The findings may also represent an interesting example of exon deletions that exert a beneficial effect on protein structure and human health.

A longstanding question in neurodevelopmental biology has been whether, or to what degree, traits resulting from neurodevelopmental disorders might be reversible.

In a , a team led by Guoping Feng of the McGovern Institute for Brain Research at MIT and the Stanley Center for Psychiatric Research at Ó³»­´«Ã½, McGovern’s Yuan Mei, and Ó³»­´«Ã½â€™s Patricia Monteiro, looked at mice born with impairments to Shank3, a gene known to contribute to a subset of autism cases. By reactivating the gene at different times of development, the researchers found that certain behavioral abnormalities caused by the impairment to Shank3, such as social deficits and repetitive behaviors, could be rescued even in adulthood, while other traits, such as anxiety and motor coordination deficits, could only be rescued early in development. The findings inform our understanding of brain plasticity and suggest that therapeutic interventions for neurodevelopmental disorders may be more effective if delivered early in development. .

Genetic disorders are often hard to model. This is particularly true for those caused by non-allelic homologous recombinations (NAHR) — which occur when highly similar portions of the genome wrongly recombine. A new study from Ó³»­´«Ã½ associate members James Gusella and Michael Talkowski, both of Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), and first author Derek J.C. Tai, also of MGH and HMS, describes a new method for using the genome engineering tool CRISPR/Cas-9 that accurately models NAHR abnormalities. Find out more about this new approach and what it means for the study of genetic disorders in .