Genetics

Boosting targeted genome editing using the hei-tag

1. Thomas Thumberger
2. Tinatini Tavhelidse-Suck
3. Jose Arturo Gutierrez-Triana
4. Alex Cornean
5. Rebekka Medert
6. Bettina Welz
7. Marc Freichel
8. Joachim Wittbrodt

• Curated by eLife

  Evaluation Summary:

  The authors describe the hei-tag, which, when added to a genome editing enzyme, results in increased editing rates in fish embryos and mammalian cell culture. The hei-tag tool could provide a valuable alternative that can potentially boost genome editing efficiency in different species and systems. The wider applicability of this approach still requires further investigation, since the improvement of editing efficiency is so far supported by experimental data on only a few targets. It would also be important to learn how the authors' design decisions affect activity, especially when benchmarked against current state-of-art genome editing tools.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Precise in vivo functional analysis of DNA variants with base editing using ACEofBASEs target prediction

1. Alex Cornean
2. Jakob Gierten
3. Bettina Welz
4. Juan Luis Mateo
5. Thomas Thumberger
6. Joachim Wittbrodt

• Curated by eLife

  Evaluation Summary:

  This is an important study that comprehensively compares the activities of different base editors in both medaka and zebrafish. The authors also provide a web tool for experimental design allowing approximately 30% of known human disease associated nucleotide variants to be modeled in fish with validated editors within days following injection. While other studies have shown similar activities in zebrafish, the authors nicely demonstrate the ability to generate phenotypes using different base editors in both zebrafish and medaka that correlate with specific base changes. This gene editing system coupled with the ability to design gRNAs efficiently with a web interface will likely have a lasting impact on the field.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Maintenance of copy number variation at the human salivary agglutinin gene ( DMBT1 ) by balancing selection driven by host-microbe interactions

1. Adel F. Alharbi
2. Nongfei Sheng
3. Katie Nicol
4. Nicklas Strömberg
5. Edward J. Hollox

Reviewed by PeerRef

Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans

1. Kelsie RS Doering
2. Xuanjin Cheng
3. Luke Milburn
4. Ramesh Ratnappan
5. Arjumand Ghazi
6. Dana L Miller
7. Stefan Taubert

• Curated by eLife

  Evaluation Summary:

  This study brings new insight into how organisms maintain homeostasis under stress conditions and has implications for our understanding both development and disease. The study provides evidence that NHR-49 protects animals from hypoxia by activating autophagy, and that it acts independently of the well-described canonical HIF-1 hypoxia response. The experiments are well done, and the conclusions from the results are largely appropriate. The impact of this study will be highest in the specific field of hypoxia, with more moderate impact for wider audiences interested in understanding of how biological maintain homeostasis under stress.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Genetic variation in ALDH4A1 is associated with muscle health over the lifespan and across species

1. Osvaldo Villa
2. Nicole L Stuhr
3. Chia-an Yen
4. Eileen M Crimmins
5. Thalida Em Arpawong
6. Sean P Curran

• Curated by eLife

  Evaluation Summary:

  This paper is of interest to researchers studying muscle function in the nematode C. elegans and to researchers interested in muscle aging in humans. The work documents the importance of C. elegans alh-6, which encodes a proline catabolic gene, in limiting muscle stress and maintaining locomotory function in aging nematodes. Further work implicates GWAS SNPs in the human homolog ALDH4A1 as potential determinants of specific muscle decline indicators. The suggestion of a conserved role for ALH-6 in aging humans could underlie establishment of a useful biomarker for older age muscle-associated health. However, while the work expands on and reinforces findings in C. elegans, it does not yet rigorously demonstrate a role for ALDH4A1 in muscle function in aging humans.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Loss-of-function mutation survey revealed that genes with background-dependent fitness are rare and functionally related in yeast

1. Elodie Caudal
2. Anne Friedrich
3. Arthur Jallet
4. Marion Garin
5. Jing Hou
6. Joseph Schacherer

Reviewed by Review Commons

Body mass index and adipose distribution have opposing genetic impacts on human blood traits

1. Christopher S Thom
2. Madison B Wilken
3. Stella T Chou
4. Benjamin F Voight

• Curated by eLife

  Evaluation Summary:

  The study investigates obesity and adipose distribution on hematopoiesis. It shows that genetically determined adiposity plays a previously underappreciated role in determining blood cell formation and function. The authors performed all the relevant and available MR analyses in the "toolbox". The results support the conclusions. The study will help understand the pathogenesis for clonal hematopoiesis.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Application of ATAC-Seq for genome-wide analysis of the chromatin state at single myofiber resolution

1. Korin Sahinyan
2. Darren M Blackburn
3. Marie-Michelle Simon
4. Felicia Lazure
5. Tony Kwan
6. Guillaume Bourque
7. Vahab D Soleimani

• Curated by eLife

  Evaluation Summary:

  In this paper, Sahinyan and colleagues developed a method for analyzing chromatin accessibility in single murine myofibers. This goal was achieved by adapting the previously published OMNI-ATAC protocol to the specific properties of the myofiber environment. To demonstrate the validity of this method, they isolated myofibers from uninjured and regenerating murine EDL muscles dissected from wild type animals. In a second experiment, this method was applied to isolate myofibers from mdx mice, a model of Duchenne Muscular Dystrophy. The resulting datasets were further compared to the one generated from purified muscle stem cells.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Tutorial: Investigating SARS-CoV-2 evolution and phylogeny using MNHN-Tree-Tools

1. Thomas Haschka

Reviewed by ScreenIT

Mendelian randomization suggests a bidirectional, causal relationship between physical inactivity and adiposity

1. Germán D Carrasquilla
2. Mario García-Ureña
3. Tove Fall
4. Thorkild IA Sørensen
5. Tuomas O Kilpeläinen

• Curated by eLife

  Evaluation Summary:

  The manuscript by Carrasquilla and colleagues applied Mendelian Randomization (MR) techniques to study causal relationship of physical activity and obesity. Their results support the causal effects of physical activity on obesity, and bi-directional causal effects of sedentary time and obesity. One strength of this work is the use of CAUSE, a recently developed MR method that is robust to common violations of MR assumptions. The conclusion reached could potentially have a large impact on an important public health problem.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife