Genetics

Chromosome structure in Drosophila is determined by boundary pairing not loop extrusion

1. Xinyang Bing
2. Wenfan Ke
3. Miki Fujioka
4. Amina Kurbidaeva
5. Sarah Levitt
6. Mike Levine
7. Paul Schedl
8. James B Jaynes

• Curated by eLife

  eLife assessment

  This valuable work presents elegant experimental data from the Drosophila embryo supporting the notion that interactions among specific loci, called boundary elements, contribute to topologically associated domain (TAD) formation and gene regulation. The evidence supporting boundary:boundary pairing as a determinant of 3D structures is compelling; however, an inability to deplete loop extruders formally leaves open a possible contribution of loop extrusion. This study will be of interest to the nuclear structure community, particularly those using Drosophila as a model.

Reviewed by eLife

Poseidon – A framework for archaeogenetic human genotype data management

1. Clemens Schmid
2. Ayshin Ghalichi
3. Thiseas C. Lamnidis
4. Dhananjaya B. A. Mudiyanselage
5. Wolfgang Haak
6. Stephan Schiffels

• Curated by eLife

  eLife assessment

  This paper describes an important software framework for the curation, retrieval, and analysis of ancient human genomic data and their associated metadata, overcoming long-standing coordination and harmonization issues in ancient human genomics. The resource is built on compelling and sometimes exceptional principles of software engineering and reproducibility, and the authors make an excellent case that their resource will be of practical use to many researchers studying human history using DNA. The main issues include natural uncertainties regarding future funding and maintenance of this resource, as well as deviation from established standards in other areas of genomics.

Reviewed by eLife

Multiplexed Assays of Human Disease-relevant Mutations Reveal UTR Dinucleotide Composition as a Major Determinant of RNA Stability

1. Jia-Ying Su
2. Yun-Lin Wang
3. Yu-Tung Hsieh
4. Yu-Chi Chang
5. Cheng-Han Yang
6. YoonSoon Kang
7. Yen-Tsung Huang
8. Chien-Ling Lin

• Curated by eLife

  eLife assessment

  This valuable study combines massively parallel reporter assays and regression analysis to identify sequence features in untranslated regions that contribute to mRNA stability. The strength of evidence presented is generally solid, but providing more details about how half lives are calculated and explaining some aspects of the subsequent choices made for analysis would clarify and strengthen the overall approach. Taken together, this study will be of interest to researchers broadly studying post-transcriptional gene regulation and also to scientists using massively parallel reporter assays.

Reviewed by eLife

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. Wenjuan Pu
6. Wendong Weng
7. Shaohua Zhang
8. Huan Zhao
9. Kathy O. Lui
10. Bin Zhou

• Curated by eLife

  eLife assessment:

  This study describes a new set of genetic tools for optimized Cre-mediated gene deletion in mice. The advances are substantial and will facilitate biomedical research. Although the tools have been validated using solid methodologies, the quantitative assessment of their recombination efficiency is not yet sufficiently described. Evaluating their ability to mediate the deletion of multiple alleles in a mosaic setting would also be a highly valuable addition.

Reviewed by eLife

A genome-wide association study implicates the olfactory system in Drosophila melanogaster diapause-associated lifespan extension and fecundity

1. Sreesankar Easwaran
2. Denise J. Montell

• Curated by eLife

  eLife assessment

  This useful study shows how genetic variation is associated with fecundity following a period of reproductive diapause in female Drosophila. The work identifies the olfactory system as central to successful diapause with associated changes in longevity and fecundity. While the genetic screening and methods used are solid, the approach to assessing diapause is incomplete and could benefit from additional orthogonal experiments.

Reviewed by eLife

ASAR lncRNAs control DNA replication timing through interactions with multiple hnRNP/RNA binding proteins

1. Mathew Thayer
2. Michael B Heskett
3. Leslie G Smith
4. Paul T Spellman
5. Phillip A Yates

• Curated by eLife

  eLife assessment

  This important study expands generally upon our understanding of the role of hnRNP proteins in lncRNA function through analysis of ASAR genes that are present on all chromosomes and of profound significance. The findings provide convincing evidence linking ASARs with the phenomenon of RNA retention on chromosomes, including X inactivation, thereby providing an expanded context for studies in these areas. This manuscript will be of interest to researchers studying gene regulation and the interactions and functional roles of hnRNP and lncRNAs.

Reviewed by eLife

mtDNA “Nomenclutter” and its Consequences on the Interpretation of Genetic Data

1. Vladimir Bajić
2. Vanessa Hava Schulmann
3. Katja Nowick

Reviewed by Peer Community in Evolutionary Biology

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.

Reviewed by eLife

Impaired central pattern generators due to abnormal EPHA4 signaling leads to idiopathic scoliosis

1. Lianlei Wang
2. Sen Zhao
3. Xinyu Yang
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

  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