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Resource: Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease
- Kangli Wang,
- Weikun Xia,
- Yingli Gu,
- Songpeng Zu,
- Qian Yang,
- Maria Luisa Amaral,
- Yaozhi Wang,
- Allen Wang,
- Xiang-Dong Fu,
- William C. Mobley,
- and Bing Ren
Genome Res. March 4, 2026 gr.281113.125; Published in Advance March 4, 2026, doi:10.1101/gr.281113.125
...investigation into aging mechanisms. While traditional aging studies often compare just two age 76 groups, a more nuanced approach incorporating multiple age points can detect molecular 77 changes that may occur at different stages of aging, enhancing our understanding of aging 78 processes. Mice, for example...
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Research: A novel quantitative trait locus implicates Msh3 in the propensity for genome-wide short tandem repeat expansions in mice
- Mikhail O. Maksimov,
- Cynthia Wu,
- David G. Ashbrook,
- Flavia Villani,
- Vincenza Colonna,
- Nima Mousavi,
- Nichole Ma,
- Lu Lu,
- Jonathan K. Pritchard,
- Alon Goren,
- Robert W. Williams,
- Abraham A. Palmer,
- and Melissa Gymrek
Genome Res. May 2023 33: 689-702; Published in Advance May 1, 2023, doi:10.1101/gr.277576.122
.... Corresponding author: mgymrek@ucsd.eduAbstractShort tandem repeats (STRs) are a class of rapidly mutating genetic elements typically characterized by repeated units of 1–6 bp. We leveraged whole- sequencing data for 152 recombinant inbred (RI) strains from the BXD family of mice to map loci that modulate -wide...
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Research: Identification and validation of supervariants reveal novel loci associated with human white matter microstructure
- Shiying Wang,
- Ting Li,
- Bingxin Zhao,
- Wei Dai,
- Yisha Yao,
- Cai Li,
- Tengfei Li,
- Hongtu Zhu,
- and Heping Zhang
Genome Res. January 2024 34: 20-33; Published in Advance December 12, 2023, doi:10.1101/gr.277905.123
...loci associated with white matter microstructure. However, GWASs suffer from limited reproducibility and difficulties in detecting multi-single-nucleotide polymorphism (multi-SNP) and epistatic effects. In this study, we adopt the concept of supervariants, a combination of alleles in multiple loci...
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Research: Strong bias in long-read sequencing prevents assembly of Drosophila melanogaster Y-linked genes
- A. Bernardo Carvalho,
- Bernard Y. Kim,
- and Fabiana Uno
Genome Res. January 2026 36: 71-82; Published in Advance October 1, 2025, doi:10.1101/gr.280604.125
..., the clearest one against GA-rich repeats in the human . However, our study reveals a systematic failure of both technologies to sequence and assemble specific exons of Drosophila melanogaster genes, indicating an overlooked limitation. Namely, multiple Y-linked exons are nearly or completely absent from raw...
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Method: Identification of the shortest species-specific oligonucleotide sequences
- Ioannis Mouratidis,
- Maxwell A. Konnaris,
- Nikol Chantzi,
- Candace S.Y. Chan,
- Michail Patsakis,
- Kimonas Provatas,
- Austin Montgomery,
- Fotis A. Baltoumas,
- Congzhou M. Sha,
- Manvita Mareboina,
- Georgios A. Pavlopoulos,
- Dionysios V. Chartoumpekis,
- and Ilias Georgakopoulos-Soares
Genome Res. February 2025 35: 279-295; Published in Advance January 2, 2025, doi:10.1101/gr.280070.124
....29-fold, and 4.21-fold enriched at human quasi-prime loci, respectively. These findings indicate that nucleic quasi-primes are genomic loci linked to the evolution of species-specific traits, and in humans, they provide insights in the development of cognitive traits and human diseases, including...
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Method: Measuring X-Chromosome inactivation skew for X-linked diseases with adaptive nanopore sequencing
- Sena A. Gocuk,
- James Lancaster,
- Shian Su,
- Jasleen K. Jolly,
- Thomas L. Edwards,
- Doron G. Hickey,
- Matthew E. Ritchie,
- Marnie E. Blewitt,
- Lauren N. Ayton,
- and Quentin Gouil
Genome Res. November 2024 34: 1954-1965; Published in Advance September 16, 2024, doi:10.1101/gr.279396.124
.... 2020). However, such methods provide incomplete information owing to the lack of informative polymorphisms found in >20% of individuals (Onozawa et al. 2015), quantitatively limited analysis of just a few CpG sites and one or two genomic loci with the potential for PCR bias, the requirement...
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Method: Genotyping of selected germline adaptive immune system loci using short-read sequencing data
- Michael K.B. Ford,
- Ananth Hari,
- Meredith Yeager,
- Lisa Mirabello,
- Stephen Chanock,
- Ibrahim Numanagić,
- COVNET Consortium,
- and S. Cenk Sahinalp
Genome Res. September 2025 35: 2076-2086; Published in Advance August 5, 2025, doi:10.1101/gr.280314.124
...comprise the alpha (TRA), beta (TRB), delta (TRD), and gamma (TRG) variable genes. All these loci share the same fundamental structure, containing multiple copies of different classes of short genes, which are ultimately recombined through V(D)J recombination to encode the receptor protein. Of these genes...
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Research: Modest increase in the de novo single-nucleotide mutation rate in house mice born by assisted reproduction
- Laura Blanco-Berdugo,
- Alexis Garretson,
- and Beth L. Dumont
Genome Res. January 2026 36: 50-60; Published in Advance November 13, 2025, doi:10.1101/gr.281180.125
...natural- and ART-born mice (Fig. 3B). The number of dnSNVs in ART-derived mice is modestly increased within LINEs, but the difference does not reach statistical significance after applying a multiple test correction (Fisher's exact test, Bonferroni-corrected P > 0.05) (Fig. 3C). Despite an overall...
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Method: Homozygous editing of multiple genes for accelerated generation of xenotransplantation pigs
- Xiaoyue Duan,
- Chaolei Chen,
- Chang Du,
- Liang Guo,
- Jun Liu,
- Naipeng Hou,
- Pan Li,
- Xiaolan Qi,
- Fei Gao,
- Xuguang Du,
- Jiangping Song,
- and Sen Wu
Genome Res. May 2025 35: 1167-1178; Published in Advance March 5, 2025, doi:10.1101/gr.279709.124
...for V2.1G-selected (V; V2.1G) and control (C; control) cell pools. Control pools consist of transfected positive cells. Primers detect left and right junctions in CMAH and GGTA1 loci, with “GAPDH” as a normalization control. (C) Analysis of triple gene knockout in “3KO + 6KI” cell pools. (D) Ratio...
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Research: The rate and spectrum of new mutations in mice inferred by long-read sequencing
- Eugenio López-Cortegano,
- Jobran Chebib,
- Anika Jonas,
- Anastasia Vock,
- Sven Künzel,
- Peter D. Keightley,
- and Diethard Tautz
Genome Res. January 2025 35: 43-54; Published in Advance December 2, 2024, doi:10.1101/gr.279982.124
...of a large DNA satellite in MA sample 2 of BL6 (Supplemental Fig. S8). The same mechanism could also explain previous results in mice involving tandemly repeated small nucleolar regulatory RNA (SNORD) loci, in which inter-generational changes in the copy number of SNORD repeats were observed (Keshavarz et al...
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