Genetic variation can predispose to disease both through (i) monogenic risk variants that
disrupt a physiologic pathway with large effect on disease and (ii) polygenic risk that involves …

Following Cas9 cleavage, DNA repair without a donor template is generally considered
stochastic, heterogeneous and impractical beyond gene disruption. Here, we show that template-…

Although base editors are widely used to install targeted point mutations, the factors that
determine base editing outcomes are not well understood. We characterized sequence-activity …

… Christopher Cassa and Rumi Chunara contributed equally to … Cassa) and by NLM grant
LM009776 (Dr. Chunara and Dr. … Cassa, Harvard Medical SchoolBrigham and Women's …

Using optical microscopy, we investigated the heterogeneous nucleation of ice in aqueous (NH
4 ) 2 SO 4 ‐H 2 O particles containing two types of mineral dusts, kaolinite and …

The evolutionary cost of gene loss is a central question in genetics and has been investigated
in model organisms and human cell lines 1, 2, 3. In humans, tolerance of the loss of one or …

Despite major progress in defining the genetic basis of Mendelian disorders, the molecular
etiology of many cases remains unknown. Patients with these undiagnosed disorders often …

The genetic basis of most traits is highly polygenic and dominated by non-coding alleles. It
is widely assumed that such alleles exert small regulatory effects on the expression of cis-…

Background There is tremendous potential for genome sequencing to improve clinical diagnosis
and care once it becomes routinely accessible, but this will require formalizing research …

Patterns of amino acid conservation have served as a tool for understanding protein evolution
1 . The same principles have also found broad application in human genomics, driven by …