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This Week in Science: May 18, 2012

Two papers published online in advance in Science this week demonstrate an abundance of rare variants in human populations as well as a need for large sample sizes in population-based genomic analyses.

First, a team led by investigators at the University of Washington reports having sequenced 15,585 human protein-coding genes in 2,440 individuals of European and African ancestry, through which it identified more than 500,000 single-nucleotide variants, most of which were rare. "This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection," the authors write in Science. "Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits." (Last week in Science, Cornell University's Alon Keinan and Andrew Clark characterized signatures of such accelerated growth in human populations.)

As The New York Times' Nicholas Wade puts it, "these findings may help explain why it has proved so hard to isolate the genetic roots of disease. Until now, researchers have looked only at common mutations as possible contributors to the risk of common diseases."

In the second study, a public-private team led by researchers at GlaxoSmithKline shows that "due to rapid population growth and weak purifying selection, human populations harbor an abundance of rare variants, many of which are deleterious and have relevance to understanding disease risk." Sequencing 212 genes encoding drug targets in 14,002 individuals, (predominantly of European ancestry, but also of African American and South Asian roots) the researchers found that "rare variants are abundant — one every 17 bases — and geographically localized, such that even with large sample sizes, rare variant catalogs will be largely incomplete," they write.

Nature's Erika Check Hayden adds that "because many of the rare variants found in the studies were unique to specific populations with different geographic origins, variants linked to a particular disease risk in some groups won't explain the same disease in others."

Over in this week's issue of Science, Alexander Bick, Sarah Calvo, and Vamsi Mootha at Massachusetts General Hospital show that "several bacterial genomes … contain putative MCU [membrane-spanning pore subunit] homologs that may represent prokaryotic calcium channels," suggesting to them that "the uniporter may have been an early feature of mitochondria."

The Scan

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In a Novartis-sponsored study in the New England Journal of Medicine, researchers found that a CRISPR-Cas9-based treatment targeting promoters of genes encoding fetal hemoglobin could reduce disease symptoms.

Gut Microbiome Changes Appear in Infants Before They Develop Eczema, Study Finds

Researchers report in mSystems that infants experienced an enrichment in Clostridium sensu stricto 1 and Finegoldia and a depletion of Bacteroides before developing eczema.

Acute Myeloid Leukemia Treatment Specificity Enhanced With Stem Cell Editing

A study in Nature suggests epitope editing in donor stem cells prior to bone marrow transplants can stave off toxicity when targeting acute myeloid leukemia with immunotherapy.