Genetics

Base editing strategies to convert CAG to CAA diminish the disease-causing mutation in Huntington’s disease

1. Doo Eun Choi
2. Jun Wan Shin
3. Sophia Zeng
4. Eun Pyo Hong
5. Jae-Hyun Jang
6. Jacob M Loupe
7. Vanessa C Wheeler
8. Hannah E Stutzman
9. Ben Kleinstiver
10. Jong-Min Lee

• Curated by eLife

  eLife assessment

  This proof-of-concept study focuses on an A->G DNA base editing strategy that converts CAG repeats to CAA repeats in the human HTT gene, which causes Huntington's disease (HD). These studies are conducted in human HEK293 cells engineered with a 51 CAG canonical repeat and in HD knock-in mice harboring 105+ CAG repeats. The findings of this study are valuable for the HD field, applying state-of-the-art techniques. However, the key experiments have yet to be performed in neuronal systems or brains of these mice: actual disease-rectifying effects relevant to patients have yet to observed, leaving the work incomplete.

Reviewed by eLife

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. Shiro Ikegawa
33. James Lupski
34. Jonathan J Rios
35. Carol A Wise
36. Jianguo Zhang
37. Chengtian Zhao
38. Nan Wu

• Curated by eLife

  eLife assessment

  The authors combined human genetic analysis with zebrafish experiments to produce evidence that alleles that impair the function of EPHA4 cause idiopathic scoliosis (IS), a common spinal deformity. The significance of the findings is important because the cellular and molecular mechanisms that contribute to IS remain poorly understood. The human genetic data are quite convincing whereas the zebrafish data, although supportive, are incomplete.

Reviewed by eLife

SCC3 is an axial element essential for homologous chromosome pairing and synapsis

1. Yangzi Zhao
2. Lijun Ren
3. Tingting Zhao
4. Hanli You
5. Yongjie Miao
6. Huixin Liu
7. Lei Cao
8. Bingxin Wang
9. Yi Shen
10. Yafei Li
11. Ding Tang
12. Zhukuan Cheng

• Curated by eLife

  eLife assessment

  This fundamental study elucidates the function of the cohesin subunit SCC3 in maintaining homologous chromosome pairing and synapsis during meiosis. The observation of sterility in the SCC3 weak mutant prompted an investigation of abnormal chromosome behavior during anaphase I, and the discovery that SCC3's loading onto meiotic chromosomes is REC8-dependent. The convincing evidence presented in this study contributes to our understanding of meiosis in rice and attracts cell biologists, reproductive biologists, and plant geneticists.

Reviewed by eLife

Functional characterisation of rare variants in genes encoding the MAPK/ERK signalling pathway identified in long-lived Leiden Longevity Study participants

1. Helena Hinterding
2. Maarouf Baghdadi
3. Thies Gehrmann
4. Pasquale Putter
5. Mara Neuerburg
6. Nico Lakenberg
7. Erik B. van den Akker
8. P. Eline Slagboom
9. Joris Deelen
10. Linda Partridge

Reviewed by Review Commons

Mitochondrial stress in GABAergic neurons non-cell autonomously regulates organismal health and aging

1. Laxmi Rathor
2. Shayla Curry
3. Youngyong Park
4. Taylor McElroy
5. Briana Robles
6. Yi Sheng
7. Wei-Wen Chen
8. Kisuk Min
9. Rui Xiao
10. Myon Hee Lee
11. Sung Min Han

• Curated by eLife

  eLife assessment

  This study interrogates cell non-autonomous signaling between GABAergic neurons and somatic tissues in the nematode C. elegans. The authors report that mitochondrial stress in only GABAergic neurons extends lifespan and improves healthspan, phenotypes that are dependent on the transcription factor daf-16/FOXO3a. However, while the findings may be valuable to furthering our understanding of neuronal control of aging and health, the current evidence is incomplete and additional experiments are needed to support their claims.

Reviewed by eLife

Functional dissection of complex and molecular trait variants at single nucleotide resolution

1. Layla Siraj
2. Rodrigo I Castro
3. Hannah Dewey
4. Susan Kales
5. Thanh Thanh L Nguyen
6. Masahiro Kanai
7. Daniel Berenzy
8. Kousuke Mouri
9. Qingbo Wang
10. Zachary R McCaw
11. Sager J Gosai
12. François Aguet
13. Ran Cui
14. Christopher M Vockley
15. Caleb A Lareau
16. Yukinori Okada
17. Alexander Gusev
18. Thouis R Jones
19. Eric S Lander
20. Pardis C Sabeti
21. Hilary K Finucane
22. Steven K Reilly
23. Jacob C Ulirsch
24. Ryan Tewhey

Reviewed by Arcadia Science

The RNA-binding activity of the TRIM-NHL protein NHL-2 is essential for miRNA-mediated gene regulation

1. Nasim Saadat
2. Rhys N. Colson
3. Acadia L. Grimme
4. Uri Seroussi
5. Joshua W. Anderson
6. Julie M. Claycomb
7. Matthew C. J. Wilce
8. Katherine McJunkin
9. Jacqueline A. Wilce
10. Peter R. Boag

• Curated by eLife

  eLife assessment

  This useful study identifies amino acid residues in the C. elegans RNA-binding protein NHL-2 that are required for RNA binding in vitro and NHL-2 function in vivo. The evidence in support of the authors' mechanistic model is currently incomplete, as data implicating specific NHL-2 amino acids in RNA binding per se in vivo are not presented. This manuscript will be of interest to scientists working in the area of gene regulation.

Reviewed by eLife

Biobank-wide association scan identifies risk factors for late-onset Alzheimer’s disease and endophenotypes

1. Donghui Yan
2. Bowen Hu
3. Burcu F Darst
4. Shubhabrata Mukherjee
5. Brian W Kunkle
6. Yuetiva Deming
7. Logan Dumitrescu
8. Yunling Wang
9. Adam Naj
10. Amanda Kuzma
11. Yi Zhao
12. Hyunseung Kang
13. Sterling C Johnson
14. Cruchaga Carlos
15. Timothy J Hohman
16. Paul K Crane
17. Corinne D Engelman
18. Alzheimer’s Disease Genetics Consortium (ADGC)
19. Qiongshi Lu

• Curated by eLife

  eLife assessment

  In the last 15 years, large-scale association studies (GWAS) have served to estimate the association between genome-wide common variants and a large number of disparate traits and diseases in humans. This valuable method provides a new way to find correlations between the genetic component of a phenotype of interest, and all this wealth of genetic information. This software adds as a new tool to investigate genetic correlation between traits, and to generate new mechanistic hypotheses and dissect the role of the observed associations in disease heterogeneity. The results of the application of their method are solid and generally agree with what others have seen using similar AD and UKB data.

Reviewed by eLife

Natural variation in infection specificity of Caenorhabditis briggsae isolates by two RNA viruses

1. Cigdem Alkan
2. Gautier Brésard
3. Lise Frézal
4. Aurélien Richaud
5. Albane Ruaud
6. Gaotian Zhang
7. Marie-Anne Félix

Reviewed by Review Commons

Khdc3 Regulates Metabolism Across Generations in a DNA-Independent Manner

1. Liana Senaldi
2. Nora Hassan
3. Sean Cullen
4. Uthra Balaji
5. Natalie Trigg
6. Jinghua Gu
7. Hailey Finkelstein
8. Kathryn Phillips
9. Colin Conine
10. Matthew Smith-Raska

• Curated by eLife

  eLife assessment

  This important mouse study shows that wild-type female progeny of Khdc3 mutants have abnormal gene expression relating to hepatic metabolism, which persists over multiple generations and passes through both female and male lineages. Information about litter size and a full phenotypic description of the phenotype of each progeny should be included to evaluate the impact of KHDC3 mutation on the progeny; in its current state, the evidence for the authors' claims is incomplete. A role for small RNAs on this phenomenon is proposed but has not been functionally validated. The work will be of interest to researchers in the field of DNA-independent mechanism of inheritance. Mentioning the experimental organism in title and abstract would ensure that it targets the appropriate audience.

Reviewed by eLife