In Nature Genetics this week, research groups led by scientists from Amgen's DeCode Genetics report data that, collectively, comprise the largest set of human genomes sequenced from a single population. In one paper, the researchers describe sequencing the genomes of roughly 2,600 Icelanders, identifying more than 20 million genetic variants that can be combined with national healthcare records and genealogical records to provide insights into various diseases. In a separate study using these data, the scientists identify mutations, some of which present in individuals from other nations, in a gene that are associated with increase risk for Alzheimer's disease. In a third study, the investigators mine the genome data to identify more than 8,000 Icelandic individuals that have completely lost the function of at least one gene. In total, they found about 1,100 of these rare knockouts. Lastly, the researchers used whole-genome sequence data from 753 Icelandic men from 274 groups of related individuals to estimate the rate of mutation on the Y chromosome. The effort that represents the most accurate estimate of the male-specific mutation rate to date and places the most recent common ancestor for human Y chromosomes to 174,000 years to 321,000 years ago. GenomeWeb has more on this here, as does the Scan here.
Meanwhile, in Nature Biotechnology, a team from the Whitehead Institute for Biomedical Research describes a method to boost the efficiency of the genome-editing technology CRISPR/Cas9. They demonstrate that they could increase the rate at which externally supplied DNA fragments are incorporated into the genome by homologous recombination by silencing an enzyme essential to non-homologous end joining — an alternative DNA repair pathway that competes with homology-directed repair.
Lastly, in Nature Methods, scientists from Sangamo BioSciences published details of a technique to improve the specificity of transcription activator–like effector, or TALE, genome editing. By developing an expanded set of repeat variable diresidues, which TALE uses to recognize its target, to reduce off-target cleavage.