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Polymorphic inversions are ubiquitous in humans and they have been linked to both adaptation and disease. Following their discovery in Drosophila more than a century ago, inversions have proved to be more elusive than other structural variants. A wide variety of methods for the detection and genotyping of inversions have recently been developed: multiple techniques based on selective amplification by PCR, short- and long-read sequencing approaches, principal component analysis of small variant haplotypes, template strand sequencing, optical mapping, and various genome assembly methods. Many methods apply complex wet lab protocols or increasingly refined bioinformatic analyses. This review is an attempt to provide a practical summary and comparison of the methods that are in current use, with a focus on metrics such as the maximum size of segmental duplications at inversion breakpoints that each method can tolerate, the size range of inversions that they recover, their throughput, and whether the locations of putative inversions must be known beforehand.

Mammalian genomes encode over a hundred different helicases, many of which are implicated in the repair of DNA lesions by acting on DNA structures arising during DNA replication, recombination or transcription. Defining the in vivo substrates of such DNA helicases is a major challenge given the large number of helicases in the genome, the breadth of potential substrates in the genome and the degree of genetic pleiotropy among DNA helicases in resolving diverse substrates. Helicases such as WRN, BLM and RECQL5 are implicated in the resolution of error-free recombination events known as sister chromatid exchange events (SCEs). Single cell Strand-seq can be used to map the genomic location of individual SCEs at a resolution that exceeds that of classical cytogenetic techniques by several orders of magnitude. By mapping the genomic locations of SCEs in the absence of different helicases, it should in principle be possible to infer the substrate specificity of specific helicases. Here we describe how the genome can be interrogated for such DNA repair events using single-cell template strand sequencing (Strand-seq) and bioinformatic tools. SCEs and copy-number alterations were mapped to genomic locations at kilobase resolution in haploid KBM7 cells. Strategies, possibilities, and limitations of Strand-seq to study helicase function are illustrated using these cells before and after CRISPR/Cas9 knock out of WRN, BLM and/or RECQL5.

Genome in a Bottle benchmarks are widely used to help validate clinical sequencing pipelines and develop variant calling and sequencing methods. Here we use accurate linked and long reads to expand benchmarks in 7 samples to include difficult-to-map regions and segmental duplications that are challenging for short reads. These benchmarks add more than 300,000 SNVs and 50,000 insertions or deletions (indels) and include 16% more exonic variants, many in challenging, clinically relevant genes not covered previously, such as

Genome in a Bottle (GIAB) benchmarks have been widely used to help validate clinical sequencing pipelines and develop new variant calling and sequencing methods. Here we use accurate long and linked reads to expand the prior benchmark to include difficult-to-map regions and segmental duplications that are not readily accessible to short reads. Our new benchmark adds more than 300,000 SNVs, 50,000 indels, and 16 % new exonic variants, many in challenging, clinically relevant genes not previously covered (e.g., PMS2). We increase coverage of the autosomal GRCh38 assembly from 85 % to 92 %, while excluding problematic regions for benchmarking small variants (e.g., copy number variants and assembly errors) that should not have been in the previous version. Our new benchmark reliably identifies both false positives and false negatives across multiple short-, linked-, and long-read based variant calling methods. As an example of its utility, this benchmark identifies eight times more false negatives in a short read variant call set relative to our previous benchmark, mostly in difficult-to-map regions. To enable robust small variant benchmarking, we still exclude 3.6% of GRCh37 and 5.0% of GRCh38 in (1) highly repetitive regions such as large, highly similar segmental duplications and the centromere not accessible to our data and (2) regions where our sample is highly divergent from the reference due to large indels, structural variation, copy number variation, and/or errors in the reference (e.g., some KIR genes that have duplications in HG002). We have demonstrated the utility of this benchmark to assess performance in more challenging regions, which enables benchmarking in more difficult genes and continued technology and bioinformatics development. The v4.2.1 benchmarks are available under ftp://ftp-trace.ncbi.nlm.nih.gov/ReferenceSamples/giab/release/AshkenazimTrio/.

Creative Arts in Humane Medicine. Cheryl L. McLean, editor, Brush Education; 2014 This compendium of essays adds to the conversation about the place of humanities and arts in medical education. The modern version of this debate has been going on since Abraham Flexner published his famous report in

Sorrow’s Reward. Robert Allan Bear. Kingsley Publishing; 2011 Early in his medical training Robert Allan Bear came upon a copy of Edgar Lee Masters’ Spoon River Anthology . That book, published in 1915, is a work of poetic fiction about the inhabitants of the small American town of Spoon River

Combating Sleep Disorders Kathy Sexton-Radek and Gina Graci; Praeger Publishers; 2008; 152 pp $34.95 ISBN 978-0-275-98973-6

The Reason I Jump: The Inner Voice of a Thirteen-Year-Old Boy with Autism. Naoki Higashida (author), KA Yoshida, David Mitchell (translators). Random House; 2013 The Reason I Jump : it’s a curious title for a book. Why does Naoki Higashida, a 13-year-old boy with autism, jump? “When I’m

Driven to Kill: Vehicles as Weapons J. Peter Rothe University of Alberta Press; 2008. 246 pp $34.95 Let’s start with some word association. I say, “Automobile.” You say, “The demise of GM.” I say, “Car.” You might reply, “Hybrid. Or Tata Nano, the cheapest car in the world

[Figure][1] Figure. Global crises, global solutions Edited by Bjorn Lomborg, Cambridge: Cambridge University Press; 2004, 700 pp $39.95 ISBN 0-521-60614-4 Having trouble thinking clearly about the state of the world? Global Crises, Global Solutions , edited by Bjorn Lomborg, may help

Describe it simply as a lovers’ quarrel after which she slashed her wrist and sought medical attention. A superficial laceration over the right wrist. No active bleeding. Clean the area with antiseptic and pick away the dried clot. Tidy tidy. A scratch on the skin parallels the main cut

[][1] Figure. Canadian Healing Oil. I found this bottle in a little tienda (general store) on the main street of San Ignacio, Belize. The shop owner told me it was a good liniment for strains and sprains. He also made the claim that half a teaspoon taken orally was very effective for

The mindfulness meditation workshop with Dr. Jon Kabat-Zinn is scheduled to run for three hours. The afternoon begins with a 20-minute guided meditation, followed by a question-and-comment session with the workshop's 250 participants. One hour into the afternoon's activities I realize there's very

[Figure][1] Figure. Ars medica: a journal of medicine, the arts, and humanities Rex Kay, Allan Peterkin, Ronald Ruskin, editors Toronto: Department of Psychiatry, Mount Sinai Hospital 120 pp $9 Vol 1. No. 1 Fall 2004 In case you were unaware, “ Ars Medica , Canada's only literary