Genetics

ZC3H11A mutations cause high myopia by triggering PI3K-AKT and NF-κB-mediated signaling pathway in humans and mice

1. Chong Chen
2. Qian Liu
3. Cheng Tang
4. Yu Rong
5. Xinyi Zhao
6. Dandan Li
7. Fan Lu
8. Jia Qu
9. Xinting Liu

• Curated by eLife

  eLife Assessment

  This work investigates ZC3H11A as a cause of high myopia through the analysis of human data and experiments with genetic knockout of Zc3h11a in mouse, providing a useful model of myopia. The evidence supporting the conclusion is still incomplete in the revised manuscript as the concerns raised in the previous review were not fully addressed. The article would benefit from a more robust genetic analysis and comprehensive presentation of human phenotypic data to clarify the modes of inheritance in the families, currently limited by loss of patient follow-up and addressing whether there is a reduction in bipolar cell number or decreased marker protein expression through cell counts or quantifiable, less saturated Western blots. The work will be of interest to ophthalmologists and researchers working on myopia

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. Nelly M Cruz
6. Zhitao Ming
7. Julia Xia
8. Timothee Lionnet
9. Maura McGrail
10. Richard M White

• Curated by eLife

  eLife Assessment

  This important manuscript introduces a genetic tool utilizing mutant mitfa-Cas9 expressing zebrafish to knockout genes to analyze melanocyte function in development and tumorigenesis. The data are convincing and the authors cover potential caveats from their model that might impact its utility for future work. This work significantly adds to the existing approaches in the field, as the mitfa:Cas9 strategy taken here provides a roadmap for generating similar platforms for using other tissue-specific regulators and Cas proteins in the future.

Reviewed by eLife

Female-germline specific protein Sakura interacts with Otu and is crucial for germline stem cell renewal and differentiation and oogenesis

1. Azali Azlan
2. Li Zhu
3. Ryuya Fukunaga

• Curated by eLife

  eLife Assessment

  This valuable study reports the first characterization of the CG14545 gene in Drosophila melanogaster, which the authors name "Sakura." Acting during germline stem cell fate and differentiation, Sakura is required for both oogenesis and female fertility, although some mechanistic details require further investigation. This solid study presents a wide-ranging and well-controlled characterization of Sakura, and accordingly the findings and associated reagents described will be of use to scientists interested in oogenesis and early development.

Reviewed by eLife

Meta-Research: Positive genetic interactions have greater scientific impact but are under-represented in the literature

1. Mengyi Sun
2. David M. McCandlish

Reviewed by Arcadia Science

WRN and WRNIP1 ATPases impose high fidelity on translesion synthesis by Y-family DNA polymerases

1. Jung Hoon Yoon
2. Karthi Sellamuthu
3. Louise Prakash
4. Satya Prakash

• Curated by eLife

  eLife Assessment

  This manuscript reports an important finding for understanding the molecular mechanisms of mutagenesis, carcinogenesis, and senescence. It follows a previous report showing that the Werner syndrome protein WRN and its interacting protein WRNIP1 are indispensable for translesion DNA synthesis (TLS) by Y-family DNA polymerases (Pols). The manuscript provides convincing evidence that WRN and WRNIP1 ATPases, in addition to the previously reported role of the WRN 3'>5' exonuclease activity, are essential for promoting the fidelity of replication through DNA lesions by Y-family Pols in human cells.

Reviewed by eLife

A whole-organism landscape of X-inactivation in humans

1. Bjorn Gylemo
2. Maike Bensberg
3. Colm E Nestor

• Curated by eLife

  eLife Assessment

  The study provides a valuable analysis of escape from X-inactivation based on three rare female GTEX-donors with non-mosaic X-inactivation. The methods and analyses are solid and broadly support the authors' claims. Their data are more comprehensive than those presented previously and add significant weight to evidence for which genes are inactivated or escape from X inactivation in humans.

Reviewed by eLife

Direct cell-to-cell transmission of retrotransposons

1. Maya Voichek
2. Andreas Bernhard
3. Maria Novatchkova
4. Dominik Handler
5. Paul Möseneder
6. Baptiste Rafanel
7. Peter Duchek
8. Kirsten-André Senti
9. Julius Brennecke

Reviewed by preLights

The robust, high-throughput, and temporally regulated roxCre and loxCre reporting systems for genetic modifications in vivo

1. Mengyang Shi
2. Jie Li
3. Xiuxiu Liu
4. Kuo Liu
5. Lingjuan He
6. Wenjuan Pu
7. Wendong Weng
8. Shaohua Zhang
9. Huan Zhao
10. Kathy O Lui
11. Bin Zhou

• Curated by eLife

  eLife Assessment

  This study presents an important set of new tools to facilitate Cre or Dre-mediated recombination in mice. The characterization of these new tools was done using solid and validated methodology. The work convincingly demonstrates the efficient gene knockout capability of these models and will progress the field.

Reviewed by eLife

Inferring genotype-phenotype maps using attention models

1. Krishna Rijal
2. Caroline M. Holmes
3. Samantha Petti
4. Gautam Reddy
5. Michael M. Desai
6. Pankaj Mehta

Reviewed by Arcadia Science

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. Jianguo T 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