What New Genetic Discoveries Are Teaching Us About Aging, Depression, and Fertility
We Are All Mosaics—Extensive Genetic Diversity Between Cells in Older Individuals
In what Heidi Ledford described in Nature as a “technical tour de force,”¹ a recent bioRxiv preprint reported whole-genome sequencing of more than 100 individual cells from a single 74-year-old man.² What the researchers found was, in her words, pure chaos: extra chromosome arms, chromosome deletions, and smaller DNA segments altered, deleted, or duplicated. Several cells had even lost the Y chromosome entirely.
In short, nothing particularly new. It is, biologically speaking, not great getting old.
As noted in the article, this work represents the pilot phase of a $140-million consortium project aiming to catalogue somatic mutations across cells from 19 different tissues, using samples from 150 donors.
References
Ledford H. Nature. 2025;648:18.
Luquette et al. Preprint at bioRxiv. 2025. https://doi.org/10.1101/2025.10.31.685648
Sex Differences in the Genetics of Depression
Unsurprisingly, a recent comprehensive genomic analysis suggests that women carry more genetic risk variants for major depressive disorder (MDD) than men—and that these variants are strongly linked to metabolic traits.¹
These findings align with longstanding epidemiologic observations: MDD affects nearly twice as many women as men. The biological reasons underlying this disparity, however, remain unclear. Are they genetic, environmental, or—most likely—both?
The above-noted study was a large meta-analysis of genome-wide association studies (GWAS), including nearly 200,000 men and women with MDD. Among its key findings: approximately 13,200 causal variants associated with MDD in women, compared to only about 7,100 in men. Notably, all variants identified in men were also present in women, suggesting that roughly 6,100 variants are exclusive to women. The investigators additionally identified three genomic regions with significant effects on MDD only in women, strongly indicating sex-specific genetic mechanisms.
When examining genetic correlations—how genetic effects on one trait relate to another—the authors found a much stronger association between MDD and metabolic traits (including BMI and metabolic syndrome) in women than in men. This observation is consistent with the higher prevalence of metabolic symptoms among women with depression.
Several additional differences were reported, though further discussion would exceed our allotted space. The study is discussed in detail in Nature by Na Cai, PhD, of the Department of Biosystems Science and Engineering at ETH Zürich.²
References
Thomas et al. Nat Commun. 2025;16:7960.
Cai N. Nature. 2025;647:600–601.
We May Soon Be Able to Transfer Chromosomes In and Out of Cells
This is a genuinely promising story for the new year. The ability to engineer human genomes has long been viewed as science fiction—but it also holds the potential to transform both biology and human medicine.
A consortium of investigators from across Europe has now taken a first major step toward this goal by developing a method to transfer an intact human chromosome into specialized “assembly” cells, where it can be safely manipulated.¹ The engineered chromosome can then replace the corresponding chromosome in targeted human cells with minimal genetic damage.
True science fiction—now edging toward reality.
Reference
Petris et al. Science. 2025;390(6777):1038–1043.
A New Dominantly Inherited Mutation Causing Female Infertility via Preimplantation Embryo Arrest
Embryo arrest at preimplantation stages is a common cause of female infertility and is frequently encountered in IVF cycles. Although multiple genetic mutations have been implicated, much of the underlying genetic basis remains unknown.
Geminin, encoded by the GMNN gene, plays a critical role in preventing DNA re-replication by inhibiting CDT1. Using whole-exome and Sanger sequencing, investigators identified three rare missense mutations in GMNN among women experiencing preimplantation embryo arrest. Notably, these mutations follow a dominant inheritance pattern.
RNA sequencing of mouse zygotes and a patient’s one-cell embryo revealed disrupted cell-cycle regulation. The mutations were shown to reduce binding to CDT1, activate CHK1, and induce DNA damage—ultimately leading to cell-cycle disturbances and embryonic arrest.
As the authors conclude, these findings provide a mechanistic explanation for certain cases of human preimplantation embryo arrest by impairing proper DNA replication and cell-cycle control. This discovery may offer a new molecular target for both diagnosis and treatment in selected infertile women.
Reference
Zhang et al. Sci China Life Sci. 2025;68(8):2420–2430.