The biological backdrop is the GDF-15–GFRAL pathway. GDF-15 is a stress-inducible member of the TGF-beta superfamily whose highest physiological expression occurs in the placenta. From there it reaches the brainstem, where GFRAL, a glycosylphosphatidylinositol-anchored receptor expressed almost exclusively in neurons of the area postrema and the nucleus of the tractus solitarius, forms a signaling complex with the RET tyrosine kinase to transduce the hormone’s signal. Activation of this circuit produces the nausea and vomiting that make GDF-15 such a potent anorexigenic agent. Crucially, the receptor can be switched off by proteolytic cleavage: the enzyme MT1-MMP, also known as MMP14, cuts GFRAL at a juxtamembrane site, releasing a soluble ectodomain called sGFRAL and leaving behind a truncated receptor that can no longer be activated by GDF-15. In mice, haploinsufficiency or inhibition of MT1-MMP enhances GDF-15’s appetite-suppressing effects, confirming that cleavage inactivates the receptor.

Genetic evidence has already tied the pathway to hyperemesis gravidarum. Common variants in GDF15, the gene encoding the hormone, are among the strongest risk factors for the condition, and risk-associated GDF15 alleles are linked to lower baseline levels of circulating GDF-15 outside pregnancy. The prevailing model holds that women with low preconception GDF-15 remain hypersensitive to the hormone’s dramatic rise during pregnancy, whereas higher basal levels pre-condition the system and promote desensitization. But GDF15 is not the only gene implicated: common variants in GFRAL itself and in the progesterone receptor gene PGR also associate with risk. What remained unknown was whether rare GFRAL variants modulate susceptibility, and whether receptor cleavage actually occurs in human pregnancy.

To address the first question, the team sequenced the whole exomes of 926 women with hyperemesis gravidarum and 660 unaffected controls. They identified 14 rare GFRAL variants occurring exclusively in cases, including five missense variants, one of them novel and three predicted damaging by SIFT. Among these was a 5′ UTR variant, rs138536707, found at significantly elevated frequency in African American women with hyperemesis gravidarum, with an odds ratio of 2.6 in a comparison against a morning sickness clinic cohort. People of African ancestry are known to carry increased risk for the condition, making this variant of particular interest for follow-up. Another case, a woman whose illness was severe enough to require total parenteral nutrition, carried the p.Met370Thr variant at the GFRAL–RET51 interface; the authors speculate that replacing a bulky hydrophobic methionine with a polar threonine could subtly stabilize the GFRAL–RET signaling complex and slow its dissociation, though this remains hypothetical.

Variants found only in controls proved equally intriguing. Eleven rare variants absent from all cases included six missense changes, four intronic variants, and one frameshift elongation. The frameshift variant rs527905870 was identified in two controls who both reported pregnancies entirely free of nausea and vomiting, suggesting that a defective receptor might protect against pregnancy sickness. Three of the control-only missense variants, p.Pro218Ala, p.Ser222Asn, and p.Arg225His, sit at the intersection of the GDF-15 ligand-binding domain and the GDNF/GAS1 domain responsible for signal transduction, positions where altered function is plausible. The authors are careful to stress, however, that the study was not powered for quantitative enrichment analysis and that these case-exclusive and control-exclusive signals should be read as hypothesis-generating rather than as evidence of causality. GFRAL variations, they conclude, are far too infrequent to account for the majority of hyperemesis gravidarum or symptom-free pregnancies.

The study also examined whether a common non-coding GFRAL risk variant influences symptom duration. Nausea and vomiting generally resolve by the second trimester, but in hyperemesis gravidarum symptoms can persist well beyond 27 weeks’ gestation. Genotyping revealed that the risk allele rs7761177-T was associated with a 1.7-fold increased risk of prolonged disease, with an odds ratio of 1.74 and a marginal p value of 0.047 in a modest sample of 38 early-resolving and 87 prolonged cases. The team further sequenced rs10948901-T, recently identified as the strongest GFRAL risk variant in a large multi-ancestry study and used here as a proxy, but found no detectable correlation between the risk variants and circulating sGFRAL levels, leaving the mechanism linking the variant to prolonged symptoms unknown.

The serological arm of the study required building an in-house ELISA to measure sGFRAL in serum and plasma, something never before analyzed in pregnant women. The capture antibody, 3P10, binds GFRAL at the RET interaction interface centered on residue Arg294, within the MMP14-cleaved fragment. Any 3P10-reactive fragment detected in blood therefore implies a truncated membrane receptor left behind on brainstem neurons that is incapable of RET signaling, making sGFRAL a proxy for proteolytic receptor inactivation. Detection rates hovered between 37 and 47 percent across non-pregnant women and all three trimesters, without statistically significant differences. In the first trimester, however, detection was significantly higher in hyperemesis gravidarum cases, at 70 percent, than in women with ordinary nausea and vomiting of pregnancy, at 42 percent, or in symptom-free pregnancies, at 35 percent, with odds ratios of 3.35 and 4.38 respectively.

Longitudinal samples sharpened the picture. In ten women from an IVF cohort with normal pregnancy outcomes, sGFRAL was detectable in eight blood samples drawn between days 35 and 43 post-implantation, at a mean of 218.7 picograms per milliliter. Strikingly, by the second sampling between days 62 and 76, none of the eight analyzed women showed detectable sGFRAL any longer, a statistically significant drop. The only patient whose sGFRAL persisted was the one who went on sick leave because of nausea. In stark contrast, eight women receiving intravenous fluids for hyperemesis gravidarum-related dehydration showed no drop in sGFRAL between six and 12 weeks’ gestation, with means of 177.7 and 211.4 picograms per milliliter and no significant difference. Sustained receptor shedding in blood, the authors propose, may reflect persistent GFRAL synthesis in the brainstem of affected women, or more effective suppression of new synthesis in unaffected pregnancies. Notably, in the morning sickness clinic cohort, sGFRAL levels correlated inversely with early-pregnancy weight loss, consistent with a protective role of receptor cleavage.

A two-part regression model applied to the CGATE cohort at 12 and 24 weeks’ gestation added a mid-gestation dimension. Across both time points combined, women with hyperemesis gravidarum had significantly higher odds of detectable sGFRAL than symptom-free women, with an odds ratio of 3.03, while ordinary nausea and vomiting did not differ from symptom-free pregnancies. Yet among samples with detectable sGFRAL, concentrations were significantly lower in the hyperemesis gravidarum group, particularly at 24 weeks, where the fold change relative to symptom-free women was 0.339. Hyperemesis gravidarum thus differs from both comparison groups in the likelihood and in the magnitude of circulating sGFRAL, a pattern the authors interpret as altered dynamics of receptor shedding, synthesis, or both, while acknowledging that the present data cannot distinguish between the two.

The implications reach beyond pregnancy sickness. The GDF-15–GFRAL pathway is implicated in cancer cachexia and chemotherapy-induced nausea and vomiting, and pharmaceutical blockade is advancing rapidly: Pfizer’s anti-GDF-15 antibody ponesegromab safely increased weight and activity in cachexia patients, and CatalYm’s visugromab increased body weight in cancer patients with high GDF-15 levels. Clinical trials of GFRAL inhibition with the monoclonal antibody NGM120 are underway in the UK and Australia. If validated, sGFRAL analysis could serve as a novel biomarker for hyperemesis gravidarum diagnosis, risk stratification, and treatment response, and engineered sGFRAL mimetics acting as GDF-15 traps could become therapeutics for the condition and related disorders. The authors also note that in silico analysis predicts a GFRAL promoter rich in Sp1 sites with progesterone and non-canonical estrogen response elements, offering a possible explanation for the association between progesterone receptor variants and disease. Key limitations remain: low variant frequencies, small cohorts, missing ancestry data in several European samples, and the impossibility of directly measuring intact GFRAL on brainstem neurons in pregnant women. Rodents lack the vomiting reflex, making the disease difficult to model. Even so, the study opens a concrete, testable route into the receptor-level regulation of one of pregnancy’s most disabling conditions.

Subject of Research: Genetic variations in the GDF-15 receptor GFRAL and first measurements of circulating soluble GFRAL in hyperemesis gravidarum and normal pregnancy

Article Title: GFRAL genetic variations and circulating GFRAL in hyperemesis gravidarum

Article References: Haack, B., Neemuchwala, Z. H., DeVera, S., MacGibbon, K. W., Fischer, B., Höschle, F., Fasching, P. A., Housholder, A., Vanky, E., Friese, M. A., Bixo, M., Stiernman, L., Ekwurtzel, E., Nording, M., Vinnars, M.-T., Wischhusen, J., & Fejzo, M. S. (2026). GFRAL genetic variations and circulating GFRAL in hyperemesis gravidarum. iScience, 29(11), Article 117975. https://doi.org/10.1016/j.isci.2026.117975

Image Credits: AI Generated

DOI: 10.1016/j.isci.2026.117975

Keywords: hyperemesis gravidarum, GDF-15, GFRAL, pregnancy, nausea and vomiting, genetics, biomarker, brainstem, RET signaling, MMP14, genetic, variations

The selected accessions retained all alleles detected in the full collection and were distributed evenly across the PCoA plot, according to the research published in BMC Plant Biology . The researchers amplified SSR markers across the full collection and separated the products by capillary electrophoresis. The polymorphism information content ranged from 0.081 to 0.669 and averaged 0.407.

The effective number of alleles per locus ranged from 1.04 to 3.79. Across the collection, mean Shannon’s diversity index was 0.938, observed heterozygosity was 0.488, expected heterozygosity was 0.517, and Nei’s diversity index was 0.482. The researchers also used locus-based statistical methods to assess diversity and clustering.

Cluster analysis divided the 259 accessions into five groups, although some groups included accessions with identical amplification profiles. After entries sharing identical loci were excluded, the researchers identified 100 distinct accessions using the 23-primer set. They then applied an allele-maximization strategy in Powercore to choose 50 accessions for the core collection, representing 19.31% of the original collection.

Relative to the full set, the core retained 100% of the observed alleles. Its effective number of alleles and Shannon’s diversity index reached 155.20% and 137.15% of the corresponding full-collection values. Together with the even PCoA distribution, these results indicated that the selected subset was representative of the sampled diversity.

The study also reduced the molecular fingerprinting panel. Of the original 23 SSR primer pairs, 13 were selected based on the numbers of unique alleles and distinguishable accessions. These primers were used to construct a fingerprint map for the 50 core accessions, providing a compact reference for distinguishing the selected germplasm.

The authors said the core collection could support more efficient screening, conservation and utilization of garlic genetic resources, while the reduced marker panel could assist future fingerprinting work and the breeding of new varieties. The analysis was limited to the genetic variation captured by 23 SSR primer pairs in the 259 accessions studied. The supplied article was also an early version of the peer-reviewed paper and remained subject to further editorial revision.

Within those boundaries, the study produced a 50-accession subset that retained the full collection’s detected alleles, displayed comparatively even coverage in PCoA space and could be distinguished with a 13-primer fingerprinting panel.

Subject of Research: Genetic diversity and core collection construction in 259 garlic germplasm accessions using SSR markers

Article Title: Genetic diversity analysis and core collection construction of 259 garlic germplasm resources based on SSR molecular markers

Article References: Zhong, Y., Li, C., Qiao, Q., Song, Y., Wu, Z., Lu, X., Tang, Z., Liang, H., & Xie, D. (2026). Genetic diversity analysis and core collection construction of 259 garlic germplasm resources based on SSR molecular markers. BMC Plant Biology. https://doi.org/10.1186/s12870-026-09880-1

Image Credits: AI Generated

DOI: 10.1186/s12870-026-09880-1

Keywords: garlic, germplasm, genetic diversity, SSR markers, core collection, molecular fingerprinting, allele diversity, plant breeding, genetic conservation, Genetic, diversity, analysis

The team began with stringent quality control at both the marker and accession levels. From that filtering, 6,829 chromosome-anchored SNPs were retained across 94 accessions, with an overall genotype call rate of 96.65 percent. Principal component and ancestry analyses flagged two accessions, VI048152 and VI050629, as highly divergent from the rest of the collection. Once these two outliers were excluded, 2,026 SNPs remained polymorphic among the remaining 92 accessions, and independent clustering resolved two genetic groups: G1, containing 31 accessions, and G2, containing 61. Discriminant analysis of principal components clearly separated the two groups.

The diversity statistics point to a limited reservoir of variation. Overall expected heterozygosity was low, at He = 0.0215. An analysis of molecular variance attributed 18.44 percent of molecular variation to differences between the two groups and 81.56 percent to variation within groups, with a fixation index of Φ = 0.1844 (p < 0.001). Pairwise FST between G1 and G2 was 0.1421, confirming measurable but moderate differentiation between the clusters.

Linkage disequilibrium behaved in an unusual way across the genome. Rather than showing a consistent decline with physical distance, LD was highly variable and lacked a distance-dependent decay pattern, which prevented the authors from estimating a robust genome-wide LD half-decay distance. This irregularity matters for breeding applications, because the pace at which LD breaks down determines how finely association studies can map traits, and it suggests that marker density or recombination patterns in this collection warrant closer attention in future work.

To locate regions of differentiation, the researchers scanned 180 eligible 100-kilobase windows against empirical thresholds. Two windows exceeded the empirical 99th-percentile FST threshold: one on chromosome 6 at 35.4–35.5 Mb with FST = 0.907, and one on chromosome 2 at 44.1–44.2 Mb with FST = 0.301. However, neither window exceeded the empirical nucleotide-diversity-ratio thresholds, so the authors interpreted them as regions of elevated differentiation rather than confirmed selective sweeps. This distinction is important: elevated differentiation between groups does not by itself prove that natural or artificial selection has acted on these loci, and the team was careful not to overstate the evidence.

Within those two differentiated regions, the analysis identified 28 annotated genes and seven candidate SNPs, five of them intronic and two coding. These variants directly intersect five priority positional genes encoding proteins with diverse predicted functions: a pTAC5-like protein, a GBA2-type β-glucosidase, a UPL5-like E3 ubiquitin-protein ligase, an NTF2-like protein, and a SWIB/BAF60 domain-containing protein. The authors present these genes as testable targets for subsequent genomic and functional investigation rather than as validated determinants of any trait.

The practical implications follow from the combination of a narrow genetic base and substantial differentiation among accessions and groups. The two highly divergent accessions, VI048152 and VI050629, represent genetically distinctive germplasm that the authors say can be prioritized for further evaluation, potentially carrying alleles absent from the main clusters. Meanwhile, the two differentiated genomic regions and the five priority positional genes offer concrete starting points for breeders and geneticists interested in the evolutionary history and breeding value of white jute, one of the two cultivated jute species and a fiber crop of major economic importance in South Asia.

The authors are explicit about the limits of the current evidence. Denser genomic data, phenotypic evaluation, and functional validation will be required to establish the evolutionary and breeding significance of the differentiated regions and candidate genes. Until such validation is complete, the study’s contribution lies in mapping the structure of the collection, quantifying its limited diversity, and narrowing the search space for traits that could matter for jute improvement, from fiber quality to stress tolerance.

For germplasm curators, the findings also carry a curation message: a collection of 94 accessions with low expected heterozygosity may benefit from targeted acquisition of genetically distinct material, and the divergent accessions already in hand should be evaluated before new acquisitions are sought. For the wider plant-genomics community, the irregular linkage disequilibrium landscape and the chromosome-anchored SNP set provide a reference framework for association mapping in white jute, a crop whose genomic resources remain far less developed than those of major cereals. The study thus delivers both a caution about the crop’s narrow genetic foundation and a short list of genomic neighborhoods worth pursuing in the next round of research.

Subject of Research: Genetic diversity and population structure of white jute germplasm analyzed with DArTseq SNP markers

Article Title: Genetic diversity, population structure, and candidate regions of differentiation in Corchorus capsularis L. germplasm collection

Article References: Shango, A. J., Omondi, E. O., N’Danikou, S., Tchokponhoué, D. A., Ozimati, A. A., Schranz, M. E., Achigan-Dako, E. G., Venkataramana, P., Philipo, M. L., & van Zonneveld, M. (2026). Genetic diversity, population structure, and candidate regions of differentiation in Corchorus capsularis L. germplasm collection. BMC Plant Biology. https://doi.org/10.1186/s12870-026-10235-z

Image Credits: AI Generated

DOI: 10.1186/s12870-026-10235-z

Keywords: white jute, Corchorus capsularis, genetic diversity, population structure, SNP markers, linkage disequilibrium, germplasm, selective sweeps, BMC Plant Biology, World Vegetable Center, Genetic, diversity

The population-based investigation linked the Danish Twin Registry with the Danish National Patient Registry. Investigators used relevant ICD-8 and ICD-10 codes to identify rotator cuff tear diagnoses recorded between 1994 and 2014. They then estimated cumulative incidence and assessed whether a rotator cuff tear diagnosis in one twin was associated with the same diagnosis in the co-twin.

By age 70, the estimated cumulative incidence of receiving a rotator cuff tear diagnosis was 6.5% in men, with a 95% confidence interval of 6.0% to 7.2%. Among women, the corresponding estimate was 3.8%, with a 95% confidence interval of 3.4% to 4.3%. These estimates concern recorded diagnoses, which may not capture every rotator cuff tear that was present but never entered into the medical record.

For twins in which one member had received a rotator cuff tear diagnosis, the risk of the same diagnosis in the co-twin was generally higher for monozygotic than dizygotic twins. The difference was clearest among men. The preferred biometric twin model, known as the AE model, attributed 49% of the variance in liability to rotator cuff tear to additive genetic effects, with a 95% confidence interval of 27% to 70%.

Unique environmental effects accounted for the remaining 51% of the modeled variance, with a 95% confidence interval of 30% to 73%. Sex-stratified results suggested a stronger genetic contribution among men, while estimates among women were less precise. The authors characterized clinically diagnosed rotator cuff tear as a common, partially heritable musculoskeletal disorder.

Their results support considering inherited susceptibility alongside occupational and environmental exposures when assessing population-level risk and clinical management. Because the analysis was based on nationwide clinical registries rather than direct examination of every participant, it characterizes variation in liability to a recorded clinical diagnosis rather than proving that genes alone cause an individual tear.

Subject of Research: Genetic and environmental contributions to clinically diagnosed rotator cuff tears in a nationwide Danish twin cohort.

Article Title: Genetic and environmental influences on rotator cuff tears: a population-based twin study

Article References: Jørgensen, C. D., von Bornemann Hjelmborg, J., Lindahl-Jacobsen, R., & Frich, L. H. (2026). Genetic and environmental influences on rotator cuff tears: a population-based twin study. BMC Medicine. https://doi.org/10.1186/s12916-026-05284-y

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05284-y

Keywords: rotator cuff tears, twin study, heritability, Danish registries, genetic susceptibility, environmental effects, shoulder disorders, population-based research, clinical diagnoses, Genetic, environmental, influences

The study aimed to characterize the genetic diversity and population structure of the eight varieties and provide a basis for their conservation and sustainable management. Its results present the first comprehensive genetic overview of these Serbian Pramenka varieties currently bred in the country. The analysis showed a shared genetic background alongside population-specific differentiation: the varieties were related, but they were not genetically interchangeable. The authors concluded that conservation and management should account for both the diversity retained within populations and the genetic integrity of individual varieties.

Pairwise FST values revealed low to moderate differentiation overall, with Lipska showing the highest genetic distinctiveness. The separation of Lipska from the other varieties was consistently supported by multidimensional scaling and discriminant analysis of principal components, or DAPC. Together, these results indicate that Lipska has a comparatively isolated genetic background within the sampled Pramenka population. The authors identified Lipska as requiring particular attention in conservation strategies.

Closer relationships appeared between Pirotska and Karakachan, and between Svrljig and Sjenica. The researchers associated these patterns with shared ancestry and possible historical gene flow. The analysis also detected private alleles, which were particularly evident in Vlashko-Vitoroga and Karakachan. These population-specific alleles provide additional evidence that the varieties retain distinctive components of genetic variation, including in populations that showed closer relationships with other varieties.

Several microsatellite loci departed from Hardy–Weinberg equilibrium. The authors linked these deviations to demographic processes, breeding practices or possible selection signals, rather than treating them as evidence of one specific cause. The findings therefore depict eight Serbian Pramenka varieties as distinct genetic entities with a common background, shaped by historical management and local adaptation. Because the study sampled 409 unrelated animals and examined 26 microsatellite loci, its conclusions apply to the analyzed populations and markers; the abstract does not provide the full sample size for each variety or detailed results for individual loci. Even with those limits, the study supplies a broad baseline for managing Pramenka diversity and assessing the genetic distinctiveness of the country’s local sheep populations.

Subject of Research: Genetic diversity and population structure among eight indigenous Pramenka sheep varieties in Serbia

Article Title: Genetic diversity and population structure of indigenous Pramenka sheep in Serbia revealed by microsatellite analyses

Article References: Davidović, S., Erić, P., Erić, K., Cekić, B., Ćosić, I., Maksimović, N., Delić, N., Ružić-Muslić, D., & Tanasković, M. (2026). Genetic diversity and population structure of indigenous Pramenka sheep in Serbia revealed by microsatellite analyses. Frontiers in Animal Science, 7, Article 1915831. https://doi.org/10.3389/fanim.2026.1915831

Image Credits: AI Generated

DOI: 10.3389/fanim.2026.1915831

Keywords: Pramenka sheep, Serbia, microsatellite markers, genetic diversity, population structure, livestock conservation, heterozygosity, private alleles, indigenous breeds, sheep genetics, Genetic, diversity

Investigators performed primary culture of fresh liver-metastatic tissue derived from colon cancer and established CRC-X1 as a cell line of Chinese origin. Its characterization combined short tandem repeat profiling, karyotype analysis, growth measurements, drug-sensitivity testing, xenograft implantation and immunohistochemical comparison with the original patient tumor tissue. Short tandem repeat profiling confirmed CRC-X1 as a novel cell line.

CRC-X1 could be maintained stably through the 59th generation, with a population doubling time of 60 hours. Karyotype analysis found that 90% of the cells had a near-triploid karyotype and 10% had a near-tetraploid karyotype. The representative karyotype was reported as 71,XXXX, der(5), inv(9), der(11), der(22).

These measurements document the line’s propagation characteristics and highly abnormal chromosome composition in the analyzed cells. In functional testing, subcutaneous implantation of CRC-X1 cells into NCG mice produced tumors in 60% of implantations, demonstrating tumor-forming capacity in that mouse model. Immunohistochemical staining of the resulting xenograft tumors was consistent with the staining observed in the original patient tumor tissue.

Drug-sensitivity testing further showed that CRC-X1 cells were sensitive to 5-fluorouracil, also called 5-FU, but resistant to oxaliplatin. Together, these findings establish CRC-X1 as an experimental cell model for investigating colon cancer liver metastasis and screening antitumor agents. The evidence is preclinical and confined to the cultured line, its drug-sensitivity profile, and tumor formation and tissue staining in NCG mice; it does not establish clinical effectiveness in patients.

Subject of Research: Preclinical characterization of a patient-derived colon cancer liver-metastasis cell line

Article Title: Establishment and characterization of a new colon cancer cell line from liver metastases, CRC-X1

Article References: Tang, H., Miao, X., Su, Y., Zhang, Y., Yu, C., Huang, W., Wang, C., Zhu, W., Ye, Z., Jin, F., Xu, T., Chen, L., Yang, Q., Ding, J., Hu, Z., Zhang, H., Zhou, W., Chai, C., & Xu, H. (2026). Establishment and characterization of a new colon cancer cell line from liver metastases, CRC-X1. BMC Cancer. https://doi.org/10.1186/s12885-026-16798-2

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16798-2

Keywords: CRC-X1, colon cancer, liver metastasis, patient-derived cell line, xenograft model, drug sensitivity, 5-fluorouracil, oxaliplatin, karyotyping, preclinical research, Establishment, characterization

The study, conducted at the Center of Reproductive Medicine at Fujian Maternity and Child Health Hospital in Fuzhou, China, consecutively enrolled 62 couples undergoing 67 PGT-SR cycles during 2024. Four additional blastocysts from three patients in 2025 were included after their initial biopsy tests failed. The cohort comprised 42 cases involving balanced reciprocal translocations, 13 Robertsonian translocations and seven other structural abnormalities, including inversions, microdeletions, microduplications and complex rearrangements. Of 218 blastocysts available for biopsy, 211 biopsy-cell samples produced valid copy-number results initially, while seven failed initially but yielded results after a second biopsy. The researchers described the work as exploratory and hypothesis-generating rather than a demonstration that droplet testing can replace established embryo biopsy.

Biopsy-related droplets are operational by-products of trophectoderm biopsy. During the procedure, blastocoelic fluid and small amounts of embryonic cellular material can enter the surrounding biopsy, washing and temporary storage droplets. Because these droplets are already created when a clinician obtains trophectoderm cells for conventional testing, pooling them could add genetic information without requiring a separate embryo-derived fluid collection. In this study, the three droplets were combined into samples of approximately 15 microliters. Genomic DNA was amplified with the multiple annealing and looping-based amplification method, copy-number sequencing libraries were purified, and their concentrations were measured with a fluorometric assay. Sequencing was performed in paired-end mode, with at least two million reads per sample, and copy-number profiles were generated against the GRCh37/hg19 reference genome.

The researchers required a library concentration of at least 0.5 nanograms per microliter for droplet sequencing, a lower threshold than the 5 nanograms per microliter used for biopsy-cell libraries. Of the samples reaching the droplet threshold, 118 had concentrations of at least 1.0 nanogram per microliter and 33 had concentrations between 0.5 and 1.0. The researchers obtained interpretable copy-number profiles from 97.46% of the higher-concentration group and 81.82% of the lower-concentration group. Blank droplet controls produced no interpretable profiles, while trisomy 21 fibroblast controls were detected as expected. The analysis used a lower reporting threshold for deletions and duplications in droplets—10 megabases rather than 4 megabases for biopsy cells—because droplet-derived DNA was expected to be less abundant and more fragmented. Mosaic findings required an abnormal-segment proportion of at least 30%.

Among the 142 droplets with interpretable results, 87.32% agreed with biopsy findings on whether the embryo was euploid or non-euploid. Forty cases, or 40.85%, had identical copy-number profiles, while 55 cases, or 38.73%, shared at least one abnormality but also had discordant findings. The remaining 29 cases, representing 20.42%, had entirely different copy-number profiles, although 11 of these still agreed at the broader level of euploid versus non-euploid. The analysis therefore distinguished exact or overlapping chromosomal findings from ploidy-level agreement, an important qualification because a shared classification can conceal differences in individual chromosomes or segments.

Concordance was weaker when the analysis focused on the 89 blastocysts in which conventional PGT-SR detected abnormalities related to a parental structural rearrangement. Complete or partial agreement between the droplets and biopsy cells occurred in 69 cases, or 77.53%, while ploidy agreement was 83.15%. Droplet testing identified abnormalities involving the same chromosome affected by the rearrangement in 79.78% of this subgroup. Eighteen cases lacked corresponding rearrangement-related findings in the droplets: nine were below the sequencing threshold, three produced non-informative profiles after sequencing, and six contained abnormalities unrelated to the structural rearrangement. These results indicate that droplet analysis can recover rearrangement-associated information, but its lower yield and differing resolution prevent it from serving as a definitive replacement for haplotype-, breakpoint- or linkage-based PGT-SR testing.

Clinical outcomes from a small subset of transferred embryos suggested that droplet results might add information to embryo prioritization. The investigators analyzed 37 blastocysts classified as euploid by trophectoderm biopsy that were subsequently transferred. Seven had euploid droplet profiles, seven had non-euploid profiles, and 23 had undetectable or non-informative results. Clinical pregnancy occurred in six of seven embryos in the euploid-droplet group, or 85.71%, and in two of seven in the non-euploid-droplet group, or 28.57%. Twenty of the 23 embryos with undetectable or non-informative droplet results, or 86.96%, achieved clinical pregnancy. The reported clinical-pregnancy measure included ongoing pregnancies, miscarriages and live births. The group sizes were very small, the design was observational, and the analysis was restricted to embryos already classified as euploid by biopsy, so the outcome differences cannot establish that droplet testing caused the pregnancies or reliably predicted embryo viability.

Among 12 live births in the transferred cohort, prenatal chromosomal microarray analysis of amniotic fluid found no significant fetal chromosomal abnormalities. The study also examined whether droplets collected during an initial failed biopsy could help inform the decision to perform another biopsy. Initial droplet samples were interpretable for six of seven blastocysts that later underwent a second biopsy. Five were non-euploid in the droplet analysis and were also non-euploid on second biopsy, while one was euploid in both. Overall, the droplet and second-biopsy classifications agreed for six of seven embryos, or 85.71%. None of the droplets produced during the second procedure reached the sequencing threshold. These observations suggest that retaining material from the first biopsy may provide supplementary evidence when a conventional test fails, although the sample was too small to determine whether such testing should replace repeat biopsy.

Several biological and technical constraints limit interpretation. Droplet DNA may include blastocoelic fluid, occasional embryo cells and genetic material of uncertain or non-embryonic origin. Its low concentration and fragmentation can increase amplification noise, destabilize copy-number profiles and make small structural abnormalities difficult to resolve. The timing of collection may also matter: five of nine droplets below the sequencing threshold in the rearrangement subgroup were collected more than one day after biopsy. Droplet concentrations were associated with blastocyst morphology, trophectoderm grade and biopsy-based ploidy. Samples from embryos classified as non-euploid had higher mean library concentrations than those from euploid embryos, while poorer morphological grades were also associated with higher concentrations. The authors said these associations might reflect differences in cellular stress, apoptosis or fragmentation, but the biological origins of embryo-associated DNA remain incompletely understood. Null results therefore cannot be treated as evidence that an embryo is euploid, and discordant results may reflect sampling or technical differences rather than true embryonic mosaicism.

The findings support storing biopsy-related droplets for selected retrospective analysis rather than testing every embryo routinely. Possible applications include adding context to embryos classified as euploid, examining possible mosaicism missed by a localized trophectoderm sample, investigating euploid-embryo transfer failures and informing—but not automatically determining—the need for repeat biopsy. The researchers proposed that a euploid or undetectable droplet result may be supportive when prioritizing an embryo, whereas a non-euploid result may be less supportive; a non-euploid finding after repeated euploid transfer failures could also point toward an embryonic contribution, while a euploid result may prompt consideration of other factors. These interpretations remain provisional. The study was conducted at one center, involved a PGT-SR population, and relied on several small subgroups. Further optimization of collection, amplification, contamination control and analysis, together with larger independent cohorts, is required before biopsy-related droplet testing can be used as a clinically validated adjunct to conventional PGT-SR.

Subject of Research: Genetic analysis of biopsy-related droplets as an adjunct to PGT-SR

Article Title: Genetic analysis of biopsy-related droplets and its potential applications in PGT-SR patients

Article References: Huang, Z., Chen, Y., Cai, X., Zhu, S., Wang, J., Xie, R., Shi, H., Yu, A., Zheng, B., & Sun, Y. (2026). Genetic analysis of biopsy-related droplets and its potential applications in PGT-SR patients. Frontiers in Endocrinology, 17, Article 1946046. https://doi.org/10.3389/fendo.2026.1946046

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1946046

Keywords: biopsy-related droplets, preimplantation genetic testing, structural rearrangements, copy-number variation, blastocyst biopsy, next-generation sequencing, embryo mosaicism, repeat biopsy, Genetic, analysis, biopsy-related, droplets

Keloids are chronic fibroproliferative lesions marked by persistent inflammation, altered wound healing and excessive extracellular matrix deposition. Unlike ordinary scars, they continue to enlarge beyond the original wound margins and may cause itching, pain and substantial cosmetic distress. Surgery, intralesional corticosteroids, radiotherapy, laser therapy and cryotherapy can reduce lesion burden in selected patients, yet recurrence is common. The study’s focus was therefore not a clinical treatment trial, but an attempt to connect inherited variation in circulating microRNAs with molecular changes measured in established keloid tissue and primary cells.

For the genetic component, the investigators used two-sample Mendelian randomization. Genetic variants associated with plasma microRNA levels were treated as instrumental variables for the corresponding circulating microRNAs, while summary association data from the Million Veteran Program were used to assess keloid susceptibility. The miRNA quantitative-trait-locus data came from a genome-wide association study of 2,178 participants in which 2,083 plasma microRNAs were quantified. The keloid outcome analysis included 447,008 analyzable individuals. Linkage-disequilibrium clumping, removal of palindromic variants and instrument-strength checks were used to prepare the analyses, with instruments for most microRNAs represented by a single genetic variant.

Nine microRNAs showed nominal associations with keloid susceptibility, but none remained significant after correction for multiple testing. miR-539-3p had a nominal inverse genetic association, with an odds ratio of 0.68, a 95% confidence interval of 0.47 to 0.97 and a P value of 0.035; its false-discovery-rate-adjusted P value was 0.986. Because that estimate came from one SNP, the investigators could not perform candidate-specific sensitivity analyses such as MR-Egger regression, weighted median estimation or leave-one-out analysis. The result is therefore an exploratory selection signal, not evidence that higher circulating miR-539-3p protects against keloids.

The researchers next analyzed the public GEO dataset GSE237753, which contains bulk microRNA sequencing from three keloid tissues and three normal skin controls. After quality control and filtering of low-abundance microRNAs, the DESeq2 analysis identified 44 differentially expressed microRNAs. miR-539-3p was the only candidate to overlap with the nominal Mendelian-randomization results. It was strongly upregulated in keloid tissue, with a log2 fold change of 3.29 and an adjusted P value of 4.71 × 10−6. This overlap was used to prioritize the molecule for biological follow-up rather than to confirm a genetic causal effect.

Potential downstream targets were assembled from miRDB, TargetScan and miRTarBase. Nine genes appeared in all three resources: SOX9, CTBP1, NRF1, ARID1A, SRSF2, PCGF3, HS3ST3B1, KPNA2 and MTF2. Their combined annotation was associated with developmental processes, regulation of cell number, stem-cell population maintenance and extracellular matrix organization, along with transcriptional and PI3K–Akt-related functions. SOX9 was selected for further examination because it was a shared predicted target, had a curated human miR-539-3p/SOX9 record in miRTarBase, and was considered biologically relevant to mesenchymal remodeling and fibrosis. The selection combined computational prediction, curated evidence and literature-guided biological judgment.

Experimental measurements in primary cells and tissue provided further support for the expression pattern. The researchers tested eight matched pairs of normal skin-derived and keloid-derived fibroblasts from eight patients. Both miR-539-3p and SOX9 messenger RNA levels were higher in the keloid-derived cells, with P values of 3.69 × 10−5 and 1.09 × 10−5, respectively. In an independent set of 20 specimens—10 normal skin samples and 10 keloids—semiquantitative immunohistochemistry showed stronger SOX9 staining in the dermal or lesional compartment of keloids. Mean immunoreactivity scores were 4.20 ± 1.38 for keloids and 1.55 ± 0.64 for normal skin, with P = 5.18 × 10−5.

SOX9-centered networks placed the candidate within several processes relevant to scar remodeling. GeneMANIA analysis connected SOX9 with genes involved in connective-tissue development, extracellular matrix organization and mesenchyme development, with enrichment for Notch signaling, cytoskeletal processes and PI3K–Akt signaling. A high-confidence STRING network was enriched for connective-tissue and mesenchyme development, epithelial-to-mesenchymal transition, collagen-containing extracellular matrix, Wnt signaling, TGF-β signaling, Hippo signaling, Hedgehog signaling and Notch signaling. These computational associations describe the biological context around SOX9; they do not demonstrate that SOX9 controls keloid formation or directly governs matrix deposition.

The investigators also transfected primary fibroblasts with a miR-539-3p inhibitor or a negative-control oligonucleotide. Across three independent experiments per assay, SOX9 messenger RNA was higher after inhibitor treatment than after control treatment, with P = 0.0007. Western blotting likewise showed higher SOX9-to-GAPDH protein abundance after inhibition, with a nominal P value of 0.0296. The result is compatible with the possibility that miR-539-3p can influence SOX9, but direct targeting was not tested. The study did not examine whether miR-539-3p binds the SOX9 3′ untranslated region, and it did not manipulate SOX9 to determine whether the protein changes fibroblast activation or matrix production.

Several limitations constrain the conclusions. The genetic signal was nominal, based on one SNP and unable to support robust candidate-specific sensitivity testing. The microRNA-QTL exposure cohort was of European ancestry, while the multi-ethnic keloid GWAS was predominantly European, limiting generalizability. The discovery transcriptomic dataset contained only three keloid and three control tissues, and the paired-cell and tissue experiments, although independent of that dataset, assessed established lesions rather than the process of scar initiation. The differing directions of the genetic and expression findings also reflect different biological contexts: genetically predicted circulating microRNA levels were compared with molecular measurements from established lesions and lesion-derived cells. The study has therefore narrowed a broad candidate space to an experimentally tractable miR-539-3p/SOX9 association. Direct binding assays, targeted perturbation of both molecules and rescue experiments in keloid-derived cells will be needed to determine whether the relationship is direct, indirect or simply part of a broader remodeling program.

Subject of Research: Exploratory genetic, transcriptomic and experimental analysis of miR-539-3p and SOX9 expression in keloid tissue and fibroblasts

Article Title: Integrated genetic and transcriptomic analyses suggest a miR-539-3p/SOX9-associated expression pattern in keloids

Article References: Luo, Z., Ge, L., Chen, L., Lin, S., Wei, T., Lu, B., & Jin, Z. (2026). Integrated genetic and transcriptomic analyses suggest a miR-539-3p/SOX9-associated expression pattern in keloids. Frontiers in Cell and Developmental Biology, 14, Article 1931861. https://doi.org/10.3389/fcell.2026.1931861

Image Credits: AI Generated

DOI: 10.3389/fcell.2026.1931861

Keywords: keloids, fibrosis, miR-539-3p, SOX9, microRNA, Mendelian randomization, transcriptomics, extracellular matrix, primary fibroblasts, Integrated, genetic, transcriptomic

Flanagan-Steet’s research focuses on congenital disorders of glycosylation, or CDG, a group of rare inherited diseases caused by changes in genes involved in glycosylation. This process adds sugar chains to proteins and lipids and is essential to their normal function. When glycosylation is disrupted, the resulting conditions can produce a wide range of health problems, including secondary changes in how the body uses sugar metabolites. Nearly 200 inherited glycosylation disorders have been identified, but their biological mechanisms remain incompletely understood and treatment options are limited.

The award will support work examining how changes in the basic building blocks required for glycosylation affect cells and tissues, how those changes interfere with development, and how they contribute to disease. The researchers will also study the connection between altered metabolism and impaired glycosylation, two processes that may jointly shape normal development and disease onset. This approach is intended to identify shared biological pathways across several forms of CDG, including PMM2-CDG, the most common form of the disorder.

To investigate these questions, Flanagan-Steet and her team use zebrafish models in which they can examine the effects of changes in cellular metabolism and glycosylation. Their planned work includes studies of multiple forms of CDG within the same model system, enabling researchers to look for mechanisms common to several disorders. Because this is a grant announcement, the award does not yet establish new biological findings, clinical benefits or effective treatments; it provides support for the planned research and its evolving directions.

Greenwood Genetic Center President and CEO Steve Skinner said MIRA grants give investigators with established research records greater flexibility to follow important discoveries as their programs develop. “That flexibility is particularly valuable in rare disease research, where an unexpected finding can open an entirely new avenue of investigation,” Skinner said. Flanagan-Steet said the funding will allow her team to pursue broader questions about the relationship between metabolism and glycosylation and follow new discoveries as they arise. The five-year award is intended to strengthen understanding of rare diseases and, potentially, point toward new approaches for patients and families, although that goal remains an outcome the research will need to demonstrate.

Subject of Research: Research on metabolism and glycosylation in congenital disorders of glycosylation using zebrafish models

Article Title: Greenwood Genetic Center researcher receives $1.4 million NIH grant to study metabolism and glycosylation in rare genetic diseases

Article References: Greenwood Genetic Center researcher receives $1.4 million NIH grant to study metabolism and glycosylation in rare genetic diseases. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: NIH grant, rare diseases, congenital disorders of glycosylation, metabolism, glycosylation, zebrafish models, PMM2-CDG, developmental biology, medical genetics, Greenwood, Genetic, Center

The three probands all had absent irises and nystagmus, but additional findings differed among families. The female proband in Family 1 had bilateral iris absence, punctate posterior synechiae and largely normal fundi. The female proband in Family 2 had bilateral iris absence, anterior subcapsular lens opacities, poor vision and photophobia, while her mother had bilateral iris hypoplasia. The male proband in Family 3 had iris absence, photophobia, nystagmus and foveal hypoplasia confirmed by optical coherence tomography. He also had mild intellectual disability and had been diagnosed with Wilms tumor before presenting for ophthalmic evaluation. Because only three families were studied, the authors cautioned against systematic comparisons of severity between variant classes.

In Family 1, array comparative genomic hybridization identified an approximately 3.19-megabase heterozygous deletion at 11p13, designated arr[GRCh37] 11p13(31037165_34227327) × 1. The interval encompassed all of PAX6 as well as WT1, ELP4, RCN1, CCDC73 and other genes. High-resolution karyotyping at 550–700-band resolution showed a normal 46,XX complement and did not detect the deletion. Quantitative PCR across PAX6 exons 2, 7 and 14 confirmed that the proband had a single copy, while her parents and younger sister had normal copy numbers. The variant was therefore considered de novo and was classified as pathogenic under the cited ACMG and ClinGen copy-number-variant standards.

Family 2 had a different molecular architecture. Whole-exome sequencing detected a heterozygous single-base deletion in exon 14 of PAX6, reported on the MANE Select transcript NM_001368894.2 as c.1234del, or p.Ser412ProfsTer127. The deletion occurred within a thymine homopolymer, and the resulting frameshift was predicted to begin at serine 412. Because exon 14 is the terminal coding exon, the altered transcript was predicted to escape nonsense-mediated messenger RNA decay and produce a C-terminally extended protein of 537 amino acids rather than the wild-type 436. The authors therefore considered disruption of the PST transactivation domain more likely than RNA-degradation-mediated haploinsufficiency as the pathogenic mechanism. The variant was absent from ClinVar and gnomAD at the time of analysis.

Sanger sequencing confirmed that the Family 2 proband and her affected mother carried c.1234del, whereas her father did not, establishing maternal inheritance consistent with autosomal dominant aniridia. The variant was classified as likely pathogenic using a point-based framework combining strong PVS1 evidence, supporting evidence for absence from population databases, computational prediction and phenotype specificity. Conservation analysis found the affected serine 412 residue to be highly conserved across humans, chimpanzees, rhesus macaques, pigs, cattle, rats and chickens, although the authors did not present direct functional experiments. Targeted sequencing of amniotic fluid during a subsequent pregnancy showed that the fetus did not carry the family variant. This result enabled prenatal exclusion of the known familial mutation, but it was a targeted test rather than a genome-wide assessment of all possible fetal abnormalities.

Family 3 carried another de novo deletion, detected through read-depth analysis of whole-exome data rather than by the initial karyotype. The approximately 2.998-megabase interval, seq[GRCh37] del(11)(p14.1p13) NC_000011.9:g.30352495_33350179del, encompassed all 14 exons of PAX6 and all 10 exons of WT1, together with DCDC1, DNAJC24, ELP4, RCN1 and other genes. Copy-number estimates were consistent with loss of one copy, and quantitative PCR independently confirmed the deletion in PAX6 exons 2, 7 and 14. Normal results in both parents supported a de novo origin. Like the Family 1 deletion, this copy-number variant was classified as pathogenic and met the molecular diagnostic criteria for WAGR syndrome because it included WT1.

The contrast between methods was central to the diagnosis. High-resolution chromosome karyotyping produced apparently normal results in all three probands, including the two children with megabase-scale deletions. Array comparative genomic hybridization identified the Family 1 deletion, while whole-exome read-depth analysis detected the Family 3 deletion and also identified the small frameshift in Family 2. Quantitative PCR supplied independent confirmation and helped assess carrier status within families, while Sanger sequencing validated the single-base variant, supported co-segregation and provided the targeted prenatal result. The findings therefore demonstrate diagnostic complementarity in this small sample, but they do not establish the sensitivity of each platform for aniridia more broadly. The authors noted that a prior Chinese study reported a 98.3% overall detection rate when next-generation sequencing and multiplex ligation-dependent probe amplification were combined, although that result came from a separate cohort.

The PAX6 variants all converge on loss of normal gene function, but the study suggests that genetic context can determine the broader phenotype. PAX6 encodes a transcription factor involved in development of the lens, cornea, retina and iris, and PAX6 haploinsufficiency is the principal mechanism underlying congenital aniridia. The two large deletions produced the eye phenotype by removing one copy of the gene and surrounding genomic material. The Family 2 frameshift was instead interpreted as a disruption of the terminal transactivation domain. Yet the limited sample did not support broad claims that deletion variants are consistently more severe than point variants. The extraocular findings in Family 3, including Wilms tumor and mild intellectual disability, were more plausibly associated with the larger deleted region and additional genes than with PAX6 alone, although the researchers called for further neurodevelopmental follow-up.

The inheritance patterns also created different reproductive implications. Both large deletions were de novo, leaving the parents with a low recurrence risk, subject to the possibility of gonadal mosaicism, and a 50% chance of transmission if either proband later reproduced. In Family 2, the affected mother was a heterozygous carrier and therefore had a 50% risk of passing the variant to a child; prenatal testing of the fetus examined in this study showed that it did not carry the variant. WAGR-spectrum findings in Families 1 and 3 prompted the authors to emphasize coordinated ophthalmic, renal, oncological and neurodevelopmental follow-up, including abdominal ultrasound surveillance for the child in Family 1. Overall, the report shows how integrating chromosome-level, sequencing, array and targeted molecular methods can identify aniridia variants that differ greatly in size and mechanism, while clarifying whether a deletion also carries WT1 and therefore an associated tumor risk.

Subject of Research: Genetic diagnosis of PAX6-related congenital aniridia and WAGR syndrome in three Chinese families

Article Title: Diverse PAX6 variants in three Chinese families with congenital aniridia: genotype–phenotype correlations and diagnostic implications

Article References: Ku, W.-J., Wei, T.-Y., Zhang, J.-L., Kang, M.-X., Yu, G., Liu, J.-E., Zhang, J., Hu, H.-Y., & Zhang, F. (2026). Diverse PAX6 variants in three Chinese families with congenital aniridia: genotype–phenotype correlations and diagnostic implications. Frontiers in Medicine, 13, 1978944. https://doi.org/10.3389/fmed.2026.1978944

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1978944

Keywords: PAX6, congenital aniridia, genetic diagnosis, whole-exome sequencing, copy-number variants, frameshift variant, WAGR syndrome, WT1, Wilms tumor, genetic counseling, Diverse, variants