Target discovery using biobanks and human genetics.

Large-scale biobanks can yield unprecedented insights into our health and provide discoveries of new and potentially targetable biomarkers. Several protective loss-of-function alleles have been identified, including variants that protect against cardiovascular disease, obesity, type 2 diabetes, and asthma and allergic diseases. These alleles serve as indicators of efficacy, mimicking the effects of drugs and suggesting that inhibiting these genes could provide therapeutic benefit, as has been observed for PCSK9.

Novel insight into the genetic basis of high-altitude pulmonary hypertension in Kyrgyz highlanders.

The Central Asian Kyrgyz highland population provides a unique opportunity to address genetic diversity and understand the genetic mechanisms underlying high-altitude pulmonary hypertension (HAPH). Although a significant fraction of the population is unaffected, there are susceptible individuals who display HAPH in the absence of any lung, cardiac or hematologic disease. We report herein the analysis of the whole-genome sequencing of healthy individuals compared with HAPH patients and other controls (total n = 33).

Identifying the favored mutation in a positive selective sweep.

Most approaches that capture signatures of selective sweeps in population genomics data do not identify the specific mutation favored by selection. We present iSAFE (for "integrated selection of allele favored by evolution"), a method that enables researchers to accurately pinpoint the favored mutation in a large region (∼5 Mbp) by using a statistic derived solely from population genetics signals. iSAFE does not require knowledge of demography, the phenotype under selection, or functional annotations of mutations.

Clear: Composition of Likelihoods for Evolve and Resequence Experiments.

The advent of next generation sequencing technologies has made whole-genome and whole-population sampling possible, even for eukaryotes with large genomes. With this development, experimental evolution studies can be designed to observe molecular evolution "in action" via evolve-and-resequence (E&R) experiments. Among other applications, E&R studies can be used to locate the genes and variants responsible for genetic adaptation.