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Researchers have found that a genetic mutation that effectively "breaks" the gene RNF186 confers protection against ulcerative colitis, a chronic inflammatory bowel disease.

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.

Fetal hemoglobin, which is normally replaced by adult hemoglobin a few months after birth, can ameliorate symptoms of beta-thalassemia and sickle cell anemia. Boosting fetal hemoglobin by inhibiting the transcription factor BCL11A holds therapeutic promise, but BCL11A's role in the body isn’t fully understood. To study its in vivo effects, a team led by Ó³»­´«Ã½ associate member Vijay Sankaran, Mark Daly, co-director of the Ó³»­´«Ã½â€™s Medical and Population Genetics Program, and Zdenek Sedlacek of University Hospital Motol (Czech Republic) identified and characterized three patients with an autism spectrum disorder and developmental delay who harbored deletions of the BCL11A gene. , appearing in the Journal of Clinical Investigation, provides evidence of BCL11A’s role in neurodevelopment and suggests caution when developing BCL11A-targeting therapies.

This week, Nature Genetics included papers on two new methods for leveraging large cohort studies. One paper — from the Ó³»­´«Ã½â€™s Program in (MPG) and , along with a team of collaborators — shares a powerful in genome-wide association studies (GWAS). The other — also with contributions from MPG — that vastly increases computation speed while simultaneously increasing the statistical power of large data sets.

In a recent study , Ó³»­´«Ã½-affiliated researchers Ron Do, Daniel Balick, Heng Li, Shamil Sunyaev, and David Reich challenged the theory that natural selection has been less effective removing deleterious genetic mutations in non-Africans versus West Africans over the course of human evolution. The team used simulations to show that observed mutation patterns that have been interpreted as evidence supporting the theory are not likely to reflect changes in the effectiveness of selection after the populations diverged, but are instead likely to be driven by other factors of population genetics.