Genetics

Becker muscular dystrophy mice showed site-specific decay of type IIa fibers with capillary change in skeletal muscle

1. Daigo Miyazaki
2. Mitsuto Sato
3. Naoko Shiba
4. Takahiro Yoshizawa
5. Akinori Nakamura

• Curated by eLife

  eLife Assessment

  The authors present three valuable transgenic models carrying three representative exon deletions of the dystrophin gene. The findings are supported by rigorous biochemical assays and state-of-the-art microscopy methods, although the evidence, while overall solid, is only partially developed, and some points could be improved.

Reviewed by eLife

Prolonged Cell Cycle Arrest in Response to DNA damage in Yeast Requires the Maintenance of DNA Damage Signaling and the Spindle Assembly Checkpoint

1. Felix Y Zhou
2. David P Waterman
3. Marissa Ashton
4. Suhaily Caban-Penix
5. Gonen Memisoglu
6. Vinay V Eapen
7. James E Haber

• Curated by eLife

  eLife Assessment

  This is an important study on the damage-induced checkpoint maintenance and termination in budding yeast that provides novel and convincing evidence for a role of the spindle assembly checkpoint and mitotic exit network in halting the cell cycle after prolonged arrest in response to irreparable DNA double strand breaks (DSBs). The study identifies particular components from these checkpoints that are specifically required for the establishment and/or the maintenance of a cell cycle block triggered by such DSBs. The authors propose an interesting model for how these different checkpoints intersect and crosstalk for timely resumption of cell cycling even without repairing DNA damage that has been revised by addressing the bulk of the reviewers' comments to the first version of the manuscript.

Reviewed by eLife

DNAH3 deficiency causes flagellar inner dynein arm loss and male infertility in humans and mice

1. Xiang Wang
2. Gan Shen
3. Yihong Yang
4. Chuan Jiang
5. Tiechao Ruan
6. Xue Yang
7. Liangchai Zhuo
8. Yingteng Zhang
9. Yangdi Ou
10. Xinya Zhao
11. Shunhua Long
12. Xiangrong Tang
13. Tingting Lin
14. Ying Shen

• Curated by eLife

  eLife Assessment

  This important study identifies biallelic variants of DNAH3 in unrelated infertile men and reports infertility in DNAH3 knockout mice. The authors demonstrate that compromised DNAH3 activity decreases the expression of IDA-associated proteins in the spermatozoa of human patients and knockout mice, providing convincing evidence that DNAH3 is a novel pathogenic gene for asthenoteratozoospermia and male infertility. The study will be of substantial interest to clinicians, reproductive counselors, embryologists, and basic researchers working on infertility and assisted reproductive technology.

Reviewed by eLife

Crispant analysis in zebrafish as a tool for rapid functional screening of disease-causing genes for bone fragility

1. Sophie Debaenst
2. Tamara Jarayseh
3. Hanna de Saffel
4. Jan Willem Bek
5. Matthieu Boone
6. Ivan Josipovic
7. Pierre Kibleur
8. Ronald Young Kwon
9. Paul J Coucke
10. Andy Willaert

• Curated by eLife

  eLife Assessment

  The paper presents a new pipeline for functional validation of genes known to underlie fragile bone disorders, using CRISPR-mediated knockouts and a number of phenotypic assessments in zebrafish. The solid data demonstrate the feasibility and validity of the approach, which presents a valuable tool for rapid functional validation of candidate gene(s) associated with heritable bone diseases identified from genetic studies.

Reviewed by eLife

Identifying in vivo genetic dependencies of melanocyte and melanoma development

1. Sarah Perlee
2. Yilun Ma
3. Miranda V Hunter
4. Jacob B Swanson
5. Zhitao Ming
6. Julia Xia
7. Timothée Lionnet
8. Maura McGrail
9. Richard M White

• Curated by eLife

  eLife Assessment

  This important study presents a new method for generating cell-type restricted knockouts in zebrafish and it reports several interesting applications of this method to study pigmentation and melanomagenesis. The evidence supporting the conclusions is convincing, with rigorous characterization of several knock out mutations that provide a proof of principle. The work will be of broad interest to cell, skin, and cancer biologists.

Reviewed by eLife

Dimensionality Reduction of Genetic Data using Contrastive Learning

1. Filip Thor
2. Carl Nettelblad

Reviewed by Arcadia Science

Sir2 and Fun30 regulate ribosomal DNA replication timing via MCM helicase positioning and nucleosome occupancy

1. Carmina Lichauco
2. Eric J Foss
3. Tonibelle Gatbonton-Schwager
4. Nelson F Athow
5. Brandon Lofts
6. Robin Acob
7. Erin Taylor
8. James J Marquez
9. Uyen Lao
10. Shawna Miles
11. Antonio Bedalov

• Curated by eLife

  eLife Assessment

  This valuable study is a detailed investigation of how chromatin structure influences replication origin function in yeast ribosomal DNA, with a focus on the role of the histone deacetylase Sir2 and the chromatin remodeler Fun30. Convincing evidence shows that Sir2 does not affect origin licensing but rather affects local transcription and nucleosome positioning which correlates with increased origin firing. Overall, the evidence is solid and the model plausible. However, the methods employed do not rigorously establish a key aspect of the mechanism where initiation precisely occurs or rigorously exclude alternative models and the effect of Sir2 on transcription is not re-examined in the fun30 context.

Reviewed by eLife

Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity

1. Jacob W Klemm
2. Chloe Van Hazel
3. Robin E Harris

• Curated by eLife

  eLife Assessment

  This manuscript reports fundamental discoveries on how necrotic cells contribute to organ regeneration through apoptotic signaling. These findings would be of broad interest to those who study wound repair and tissue regeneration. The strength of the evidence is solid, but would be stronger with additional quantifications and controls.

Reviewed by eLife

Sibling Similarity Can Reveal Key Insights into Genetic Architecture

1. Tade Souaiaia
2. Hei Man Wu
3. Clive Hoggart
4. Paul O’Reilly

• Curated by eLife

  eLife assessment

  The authors present a solid statistical framework for using sibling phenotype data to assess whether there is evidence for de-novo or rare variants causing extreme trait values. Their valuable method is promising and will be of interest to researchers studying complex trait genetics.

Reviewed by eLife

Single-cell eQTL mapping in yeast reveals a tradeoff between growth and reproduction

1. James Boocock
2. Noah Alexander
3. Leslie Alamo Tapia
4. Laura Walter-McNeill
5. Chetan Munugala
6. Joshua S Bloom
7. Leonid Kruglyak

• Curated by eLife

  eLife assessment

  This manuscript describes the mapping of natural DNA sequence variants that affect gene expression and its noise, as well as cell cycle timing, using as input single-cell RNA-sequencing of progeny from crosses between wild yeast strains. The method represents an important advance in the study of natural genetic variation. The findings, especially given the follow-up validation of the phenotypic impact of a mapped locus of major effect, provide convincing support for the rigor and utility of the method.

Reviewed by eLife, Arcadia Science