Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evidence from meta-analyses of the facial width-to-height ratio as an evolved cue of threat

The facial width-to-height ratio (FWHR) is the width of the face divided by the height of the upper face. There is mixed evidence for the hypothesis that the FWHR is a cue of threat and dominance in the human face. We conducted a systematic review and meta-analyses of all peer-reviewed studies (and 2 unpublished studies) to estimate the magnitude of the sex difference in the FWHR, and the magnitude of the relationship between the FWHR and threatening and dominant behaviours and perceptions. Studies were eligible for inclusion if the authors reported an analysis involving the FWHR. Our analyses revealed that the FWHR was larger in men than in women (d= .11, n = 10,853), cued judgements of masculinity in men (r= .35, n of faces = 487; n of observers = 339), and was related to body mass index (r= .31, n = 2,506). Further, the FWHR predicted both threat behaviour in men (r= .16, n = 4,603) and dominance behaviour in both sexes (r= .12, n = 948) across a variety of indices. Individuals with larger FWHRs were judged by observers as more threatening (r = .46, n of faces = 1,691; n of observers = 2,076) and more dominant (r= .20, n of faces = 603; n of observers = 236) than those with smaller FWHRs. Individuals with larger FWHRs were also judged as less attractive (r = -.26, n of faces = 721; n of observers = 335), especially when women made the judgements. These findings provide some support for the hypothesis that the FWHR is part of an evolved cueing system of intra-sexual threat and dominance in men. A limitation of the meta-analyses on perceptions of threat and dominance were the low number of stimuli involving female and older adult faces

Examples of measurement of the FWHR in faces with relatively low and high FWHRs.

<p>Examples of measurement of the FWHR in faces with relatively low and high FWHRs.</p

Effect sizes (<i>r</i>s) included in the meta-analysis on the relationships between the FWHR and threat behaviour (Panel A) and between the FWHR and perceptions of threat (Panel B).

<p>The mean weighted effect sizes <b>(</b></p><p></p><p></p><p></p><p><b><mi>r</mi></b></p><b><mo>¯</mo><p></p><mi>s</mi><p></p><p></p>)</b> are highlighted in grey, with men and women separated for Panel A and combined for Panel B. *<i>p</i> < .0001. ^aeffect size was removed from the final analysis.<p></p

Summary of the final results of the meta-analyses conducted in the current manuscript.

<p>Bolded effect sizes are significant and have confidence intervals that do not overlap zero (<i>p</i> < .05). <i>k</i> = number of samples included in the analysis. </p><p></p><p></p><p></p><p><mi>d</mi></p><mo>¯</mo><p></p><p></p><p></p> = standardized mean difference, adjusted for small sample size bias. <p></p><p></p><p></p><p><mi>r</mi></p><mo>¯</mo><p></p><p></p><p></p> = untransformed effect size coefficient (Pearson product moment correlation). CI = confidence interval.<p></p><p>Summary of the final results of the meta-analyses conducted in the current manuscript.</p

Implementation of preemptive DNA sequence–based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study

The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping.Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response–related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug–gene pairs, were deposited preemptively in the Mayo electronic health record.For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping.Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources