Genetics

EPHA4 signaling dysregulation links abnormal locomotion and the development of idiopathic scoliosis

1. Lianlei Wang
2. Xinyu Yang
3. Sen Zhao
4. Pengfei Zheng
5. Wen Wen
6. Kexin Xu
7. Xi Cheng
8. Qing Li
9. Anas M Khanshour
10. Yoshinao Koike
11. Junjun Liu
12. Xin Fan
13. Nao Otomo
14. Zefu Chen
15. Yaqi Li
16. Lulu Li
17. Haibo Xie
18. Panpan Zhu
19. Xiaoxin Li
20. Yuchen Niu
21. Shengru Wang
22. Sen Liu
23. Suomao Yuan
24. Chikashi Terao
25. Ziquan Li
26. Shaoke Chen
27. Xiuli Zhao
28. Pengfei Liu
29. Jennifer E Posey
30. Zhihong Wu
31. Guixing Qiu
32. DISCO study group (Deciphering Disorders Involving Scoliosis & COmorbidities)
33. Shiro Ikegawa
34. James R Lupski
35. Jonathan J Rios
36. Carol A Wise
37. Terry Jianguo Zhang
38. Chengtian Zhao
39. Nan Wu

• Curated by eLife

  eLife Assessment

  Genetic variants have been strongly implicated in idiopathic scoliosis (IS), however, the list of variants that are causative of IS is not complete and the cellular and molecular mechanisms that underlie IS are poorly understood. These authors combined human genetic analysis with zebrafish experiments to produce valuable evidence that alleles that impair function of EPHA4 cause IS, thereby extending our understanding of the basis of IS. The human genetic data are quite convincing but the zebrafish work lacks some validations and details.

Reviewed by eLife

Condensin I ^DC has a Functional ATPase That is Required for X-Chromosome Dosage Compensation in C. elegans

1. Bahaar Chawla
2. Suchi Jatia
3. Dillon E. Sloan
4. Gyorgyi Csankovszki

Reviewed by Review Commons

Tissue-specific responses to TFAM and mtDNA copy number manipulation in prematurely ageing mice

1. Laura S Kremer
2. Guanbin Gao
3. Giovanni Rigoni
4. Roberta Filograna
5. Mara Mennuni
6. Rolf Wibom
7. Ákos Végvári
8. Camilla Koolmeister
9. Nils-Göran Larsson

• Curated by eLife

  eLife Assessment

  This is an important study that examines the role of TFAM, a protein that helps maintain mtDNA, in mtDNA mutator mice. With convincing evidence, the authors have demonstrated that TFAM's counteractive role in mtDNA mutator mice is tissue-specific. The study does a thorough job of assessing the impact of modulating TFAM levels in a polg mutator mouse model of aging. The authors have thoroughly addressed all the points raised during the first round of review.

Reviewed by eLife

Integrating bulk and single cell RNA-seq refines transcriptomic profiles of individual C. elegans neurons

1. Alec Barrett
2. Erdem Varol
3. Alexis Weinreb
4. Seth R Taylor
5. Rebecca M McWhirter
6. Cyril Cros
7. Berta Vidal
8. Manasa Basaravaju
9. Abigail Poff
10. John A Tipps
11. Maryam Majeed
12. Chen Wang
13. Emily A Bayer
14. Molly Reilly
15. Eviatar Yemini
16. HaoSheng Sun
17. Oliver Hobert
18. David M Miller
19. Marc Hammarlund

• Curated by eLife

  eLife Assessment

  This valuable paper provides refined gene expression datasets for 52 neuron classes in C. elegans using a new method that takes advantage of the complementary strengths of bulk sequencing of flow-sorted cells and single-cell sequencing. In general, support for the paper's findings is convincing. However, more rigorous consideration of some of the method's statistical assumptions and validation of the predicted gene sets would improve the work.

Reviewed by eLife

PWWP-ADD and N-terminal domains of DNMT3B1 confer specificity for developmentally regulated CpG island methylation

1. Komal Yasmin
2. Tatyana B Nesterova
3. Neil Brockdorff

Reviewed by Review Commons

TRPγ regulates lipid metabolism through Dh44 neuroendocrine cells

1. Dharmendra Kumar Nath
2. Subash Dhakal
3. Youngseok Lee

• Curated by eLife

  eLife Assessment

  This important study reports findings that Trpγ, a type of transient receptor potential (TRP) channel expressed in Dh44-releasing neuroendocrine cells, mediates starvation-dependent lipid catabolism. Overall, the claims of the authors are supported by solid evidence. The work should be of interest to both basic and medical biologists working on lipid metabolism.

Reviewed by eLife

Functional characterization of all CDKN2A missense variants and comparison to in silico models of pathogenicity

1. Hirokazu Kimura
2. Kamel Lahouel
3. Cristian Tomasetti
4. Nicholas Jason Roberts

• Curated by eLife

  eLife Assessment

  This is a saturation mutagenesis screening of CDKN2A gene, successfully assessing the functionality of the missense variants. The work is solid and well-prosecuted. The manuscript was improved during the revision process and this work will serve as a valuable resource for diagnostic labs as well as cancer geneticists.

Reviewed by eLife

Molecular requirements for C. elegans transgenerational epigenetic inheritance of pathogen avoidance

1. Rachel Kaletsky
2. Rebecca S Moore
3. Titas Sengupta
4. Renee Seto
5. Borja Ceballos-Llera
6. Coleen T Murphy

• Curated by eLife

  eLife Assessment

  This fundamental study concerns a model for transgenerational epigenetic inheritance, the learned avoidance by C. elegans of the PA14 pathogenic strain of Pseudomonas aeruginosa. The authors test the impact of procedural alterations made in another study, by Gainey et al., which claimed that transgenerational inheritance in this paradigm lacks robustness, despite this observation having been reported in multiple papers from the Murphy lab. The authors of the present study show that by following a non-standard avoidance protocol, Gainey et al. likely biased their measurements in a way that made it hard to observe learned avoidance. The authors also highlight the importance of bacterial growth conditions, showing that expression of the trigger molecule, the bacterial P11 RNA, which is necessary and sufficient to drive the transgenerational inheritance of the avoidance phenotype, is influenced by temperature. As expression of P11 was not verified by Gainey et al., this provides another explanation for the inability to observe transgenerational epigenetic inheritance. Together, the authors provide compelling and powerful arguments that the original phenomenon is robust and that it can be reproduced in the Murphy lab by following their original protocol precisely, including the use of azide to immobilize the worms at the food source. Overall, this study not only provides guidance for investigators in this experimental paradigm, but it also provides additional understanding of the differences between naïve preference, learned preference, and transgenerational epigenetic inheritance. The present study is therefore of broad interest to anyone studying genetics, epigenetics, or learned behavior.

Reviewed by eLife

Diverse Genotype-by-Weather Interactions in Switchgrass

1. Alice H MacQueen
2. Li Zhang
3. Samuel Pattillo Smith
4. Jason E Bonnette
5. Arvid R Boe
6. Philip A Fay
7. Felix B Fritschi
8. David B Lowry
9. Robert B Mitchell
10. Francis M Rouquette
11. Yanqi Wu
12. Arbel Harpak
13. Thomas E Juenger

• Curated by eLife

  eLife Assessment

  The study reports valuable findings on the nature of genotype-by-climate interaction, parameterised in a framework that allows integrating genetics and ecophysiological variation in switchgrass. The evidence provided is solid overall but the analysis could be improved to better support some of the claims.

Reviewed by eLife

A mathematical model that predicts human biological age from physiological traits identifies environmental and genetic factors that influence aging

1. Sergiy Libert
2. Alex Chekholko
3. Cynthia Kenyon

• Curated by eLife

  eLife Assessment

  This important study developed a mathematical model to predict biological age by leveraging physiological traits across multiple organ systems. The results presented are convincing, utilizing comprehensive data-driven approaches. However, additional external validation could further strengthen its generalizability. The model provides a way to identify environmental and genetic factors impacting aging and lifespan, revealing new factors potentially affecting aging. It also shows promise for evaluating therapeutics aimed at prolonging a healthy lifespan.

Reviewed by eLife