Genetics

Identifying the genetic basis and molecular mechanisms underlying phenotypic correlation between complex human traits using a gene-based approach

1. Jialiang Gu
2. Chris Fuller
3. Peter Carbonetto
4. Xin He
5. Jiashun Zheng
6. Hao Li

• Curated by eLife

  eLife Assessment

  This valuable study characterizes the emergence of the membrane-associated periodic cytoskeleton (MPS) in the axons of human motor neurons derived from induced pluripotent stem cells. Super-resolution imaging of beta-II spectrin provides convincing evidence for the patterned assembly of spectrin-poor gaps and spectrin-rich MPS in the medial region of the axons and its enhancement by the kinase inhibitor staurosporine. The data advocates against gap formation by cytoskeleton disassembly in a continuous MPS. Instead, a continuous MPS may result from nascent MPS patches and their maturation, a model that would benefit from live imaging for validation.

Reviewed by eLife

Massively Parallel Polyribosome Profiling Reveals Translation Defects of Human Disease-Relevant UTR Mutations

1. Wei-Ping Li
2. Jia-Ying Su
3. Yu-Chi Chang
4. Hung-Lun Chiang
5. Yun-Lin Wang
6. Ang-Chu Huang
7. Yu-Tung Hsieh
8. Yi-Hsuan Chiang
9. Yen-Ling Ko
10. Bing-Jen Chiang
11. Cheng-Han Yang
12. Yen-Tsung Huang
13. Chien-Ling Lin

• Curated by eLife

  eLife Assessment

  The effort is timely and the paper carries valuable insights into the function of UTR mutations. There are still significant concerns about both the quality of the screen data, and its ability to detect significant changes in translation and their direction. Therefore, the ability of the screen to support the extensive downstream statistical analysis is limited and leaves the paper incomplete.

Reviewed by eLife

A genome-wide MAGIC kit for recombinase-independent mosaic analysis in Drosophila

1. Yifan Shen
2. Ann T Yeung
3. Payton Ditchfield
4. Elizabeth Korn
5. Rhiannon Clements
6. Xinchen Chen
7. Bei Wang
8. Michael Sheen
9. Parker A Jarman
10. Chun Han

• Curated by eLife

  eLife Assessment

  The study showcases a significant and important enhancement of the MAGIC transgenesis method, by extending it genome-wide to all chromosomes. The authors convincingly demonstrate that the MAGIC mosaic clones can be generated for genes from all, including the 4th chromosome. With this toolkit extension, the method is now most likely set to strongly rival the classical FRT/Flp recombination system for gene manipulation in flies.

Reviewed by eLife

Faroese Whole Genomes Provide Insight into Ancestry and Recent Selection

1. Iman Hamid
2. Ólavur Mortensen
3. Alba Refoyo-Martinez
4. Leivur N Lydersen
5. Anne-Katrin Emde
6. Melissa Hendershott
7. Katrin D Apol
8. Guðrið Andorsdóttir
9. Jonas Meisner
10. Kaja A Wasik
11. Fernando Racimo
12. Stephane E Castel
13. Noomi O Gregersen

• Curated by eLife

  eLife Assessment

  This paper presents an analysis of demography and selection from whole-genome sequencing of 40 Faroese, with data that are useful beyond the study region. Much of the analysis is solid, but a more fine-scale analysis of demographic history could have led to more interesting findings. In addition, there are concerns about the selection analyses, given the special nature of the studied population and sampling scheme. Finally, lack of data availability limits the broader value of the paper.

Reviewed by eLife

Inflammation-Induced Alternative Splicing in Human Endothelial Cells Reveals Genetic Mechanisms of Cardiovascular Disease Risk

1. Anna K. Golebiewski
2. Lindsey K. Stolze
3. Valentina D. Vazquez
4. Alhan Mehrabi Yazdi
5. Cecilia M. Careaga
6. Casey E. Romanoski

Reviewed by Arcadia Science

Life-history trade-offs explain local adaptation in Arabidopsis thaliana

1. Benjamin Brachi
2. Danièle L Filiault
3. Rahul Pisupati
4. Tal Dahan-Meir
5. Anna Igolkina
6. Alison Anastasio
7. Mathew S Box
8. Susan Duncan
9. Talia L Karasov
10. Envel Kerdaffrec
11. Laura Merwin
12. Timothy C Morton
13. Viktoria Nizhynska
14. Polina Yu Novikova
15. Fernando Rabanal
16. Takashi Tsuchimatsu
17. Torbjörn Säll
18. Caroline Dean
19. Svante Holm
20. Joy Bergelson
21. Magnus Nordborg

• Curated by eLife

  eLife Assessment

  This manuscript reports a large series of experiments to investigate specific aspects of plant adaptation, leveraging genetic and genomic resources of Arabidopsis thaliana. The study provides convincing evidence for local adaptation in this highly selfing plant. This is an important dataset contributing to the developing understanding of non-linear selection in plants and beyond.

Reviewed by eLife

Computer prediction and genetic analysis identifies retinoic acid modulation as a driver of conserved longevity pathways in genetically-diverse Caenorhabditis nematodes

1. Stephen A Banse
2. Christine A Sedore
3. Anna L Coleman-Hulbert
4. Erik Johnson
5. Brian Onken
6. David Hall
7. Erik Segerdell
8. E Grace Jones
9. Yuhua Song
10. Hadley Osman
11. Jian Xue
12. Elena Battistoni
13. Suzhen Guo
14. Anna C Foulger
15. Madhuri Achanta
16. Mustafa Sheikh
17. Theresa Fitzgibbon
18. John H Willis
19. Gavin C Woodruff
20. Monica Driscoll
21. Gordon J Lithgow
22. Patrick C Phillips

• Curated by eLife

  eLife Assessment

  This important study explores the power of computational methods to predict lifespan-extending small molecules, demonstrating that while these methods significantly increase hit rates, experimental validation remains essential. The study uses all-trans retinoic acid in Caenorhabditis elegans as a model, providing genetic and transcriptomic insights into its longevity effects. The data are compelling in describing a robust, computationally informed screening process for discovering compounds that extend lifespan in this species.

Reviewed by eLife

Borzoi-informed fine mapping improves causal variant prioritization in complex trait GWAS

1. Divyanshi Srivastava
2. Anya Korsakova
3. Qingbo Wang
4. Luong Ruiz
5. Han Yuan
6. David R Kelley

Reviewed by Arcadia Science

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