Pub Date : 2026-02-10Epub Date: 2025-11-29DOI: 10.1016/j.gene.2025.149929
Si-han Liu , Xiao-yan Kong , Miao Li , Shu-mei Wang
Background
Pediatric brain tumors (PBTs) are the leading type of solid tumors in children, profoundly affecting both survival rates and quality of life. Methotrexate (MTX) is an essential chemotherapy drug for treating these tumors; however, its efficacy and toxicity vary among patients due to genetic factors.
Objective
This study examined the impact of the intronic rs3780130 polymorphism in the gamma-glutamyl hydrolase (GGH) gene on MTX concentrations and related toxicities in patients with PBTs.
Methods
The GGH rs3780130 T > A polymorphism was genotyped using the Sequenom MassARRAY iPLEX platform in a cohort of 73 PBT patients.
Results
We found that children with the AA genotype had significantly higher MTX concentrations compared to those with TT and TA genotypes (P < 0.05). Additionally, the AA genotype was significantly associated with a higher incidence of hepatotoxicity relative to the TT genotype (P < 0.05). It showed a significantly lower occurrence of gastrointestinal toxicities when compared to the TA genotype (P < 0.05). Bioinformatics analysis revealed that the rs3780130 polymorphism had a significant effect on GGH expression across various tissues, suggesting a potential mechanism by which this variant modulated MTX metabolism.
Conclusion
Our findings highlight the importance of GGH polymorphisms in personalizing MTX therapy for PBT patients and emphasize the necessity for further research to explore the clinical implications of GGH genotypes in larger cohorts, ultimately aiming for more precise therapeutic strategies.
背景：儿童脑肿瘤（PBTs）是儿童实体肿瘤的主要类型，深刻影响着儿童的生存率和生活质量。甲氨蝶呤（MTX）是治疗这些肿瘤的重要化疗药物；然而，由于遗传因素，其疗效和毒性因患者而异。目的：研究γ -谷氨酰水解酶（GGH）基因rs3780130内含子多态性对pbt患者MTX浓度及相关毒性的影响。方法：使用Sequenom MassARRAY iPLEX平台对73例PBT患者的GGH rs3780130 T > A多态性进行基因分型。结果：我们发现AA基因型儿童的MTX浓度明显高于TT和TA基因型儿童（P ）。结论：我们的研究结果强调了GGH多态性对PBT患者个性化MTX治疗的重要性，并强调了进一步研究的必要性，以在更大的队列中探索GGH基因型的临床意义，最终旨在制定更精确的治疗策略。
{"title":"GGH intronic variant rs3780130 is associated with methotrexate levels in children with brain tumors","authors":"Si-han Liu , Xiao-yan Kong , Miao Li , Shu-mei Wang","doi":"10.1016/j.gene.2025.149929","DOIUrl":"10.1016/j.gene.2025.149929","url":null,"abstract":"<div><h3>Background</h3><div>Pediatric brain tumors (PBTs) are the leading type of solid tumors in children, profoundly affecting both survival rates and quality of life. Methotrexate (MTX) is an essential chemotherapy drug for treating these tumors; however, its efficacy and toxicity vary among patients due to genetic factors.</div></div><div><h3>Objective</h3><div>This study examined the impact of the intronic rs3780130 polymorphism in the gamma-glutamyl hydrolase (<em>GGH</em>) gene on MTX concentrations and related toxicities in patients with PBTs.</div></div><div><h3>Methods</h3><div>The <em>GGH</em> rs3780130 T > A polymorphism was genotyped using the Sequenom MassARRAY iPLEX platform in a cohort of 73 PBT patients.</div></div><div><h3>Results</h3><div>We found that children with the AA genotype had significantly higher MTX concentrations compared to those with TT and TA genotypes (<em>P</em> < 0.05). Additionally, the AA genotype was significantly associated with a higher incidence of hepatotoxicity relative to the TT genotype (<em>P</em> < 0.05). It showed a significantly lower occurrence of gastrointestinal toxicities when compared to the TA genotype (<em>P</em> < 0.05). Bioinformatics analysis revealed that the rs3780130 polymorphism had a significant effect on <em>GGH</em> expression across various tissues, suggesting a potential mechanism by which this variant modulated MTX metabolism.</div></div><div><h3>Conclusion</h3><div>Our findings highlight the importance of <em>GGH</em> polymorphisms in personalizing MTX therapy for PBT patients and emphasize the necessity for further research to explore the clinical implications of <em>GGH</em> genotypes in larger cohorts, ultimately aiming for more precise therapeutic strategies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149929"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2025-11-23DOI: 10.1016/j.gene.2025.149916
Marcelo Arancibia , Jefferson Rojas , M. Leonor Bustamante
Advances in genetics and genomics have transformed our understanding of personality. The observation that personality traits run in families has prompted extensive study into their heritability and underlying genetic architecture. However, there is a significant discrepancy between psychiatric classifications of personality disorders and genomic findings, suggesting a need to reorient these classifications toward a more dimensional, biologically informed perspective. This article reviews key genetic and genomic findings in personality, focusing on the “Big Five” model, which has proven consistency with genomic research. Twin studies estimate heritability accounts for about 40–50 % of personality traits, while the rest of phenotypic variation is explained by the non-shared environment, which influence personality through epigenetic changes. Genome-wide association studies (GWAS) have identified numerous genetic variants on nearly all chromosomes that influence personality traits, particularly neuroticism. These variants are involved in biological pathways such as neurogenesis and neuronal differentiation. GWAS have also revealed significant genetic correlations between personality traits and major psychiatric disorders, supporting a biological continuum between them. This supports the hypothesis which states that a typical behavioral trait is associated with many genetic variants, each contributing a very small effect. Future research should incorporate epigenetic evidence, study genetic interactions, and expand the diversity of study populations beyond European ancestry to improve the generalizability of findings.
{"title":"Heredity and personality: A review of concepts, methods, and evidence","authors":"Marcelo Arancibia , Jefferson Rojas , M. Leonor Bustamante","doi":"10.1016/j.gene.2025.149916","DOIUrl":"10.1016/j.gene.2025.149916","url":null,"abstract":"<div><div>Advances in genetics and genomics have transformed our understanding of personality. The observation that personality traits run in families has prompted extensive study into their heritability and underlying genetic architecture. However, there is a significant discrepancy between psychiatric classifications of personality disorders and genomic findings, suggesting a need to reorient these classifications toward a more dimensional, biologically informed perspective. This article reviews key genetic and genomic findings in personality, focusing on the “Big Five” model, which has proven consistency with genomic research. Twin studies estimate heritability accounts for about 40–50 % of personality traits, while the rest of phenotypic variation is explained by the non-shared environment, which influence personality through epigenetic changes. Genome-wide association studies (GWAS) have identified numerous genetic variants on nearly all chromosomes that influence personality traits, particularly neuroticism. These variants are involved in biological pathways such as neurogenesis and neuronal differentiation. GWAS have also revealed significant genetic correlations between personality traits and major psychiatric disorders, supporting a biological continuum between them. This supports the hypothesis which states that a typical behavioral trait is associated with many genetic variants, each contributing a very small effect. Future research should incorporate epigenetic evidence, study genetic interactions, and expand the diversity of study populations beyond European ancestry to improve the generalizability of findings.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149916"},"PeriodicalIF":2.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05Epub Date: 2025-11-19DOI: 10.1016/j.gene.2025.149913
Mahamane T. Diakité , Shan Sun , Anou M. Somboro , Brehima Diakité , Amadou Koné , Yaya Kassogué , Djeneba Fofana , Saidou Balam , Cheick B Traoré , Aminata Maiga , Bakarou Kamaté , Djibril Ba , Modibo Diarra , Soungou Boré , Almoustapha I. Maiga , Qi Dai , Drew Robert Nannini , Jane Holl , Robert Murphy , Lifang Hou , Mamoudou Maiga
Aim
To conduct a case-control study (pilot study) in Africa (Mali) in comparing the gut microbiota of patients with stage III colorectal cancer (CRC) using next-generation sequencing.
Methods
Shotgun sequencing was performed to characterize participants’ fecal microbiota using Illumina’s HiSeq platform. This case-control study involved newly diagnosed CRC patients (n = 23) prior to any treatment initiation, and unrelated healthy controls (n = 24) to elucidate their microbial diversity and relative abundance.
Results
The findings revealed that the gut microbiota in CRC and in healthy were significantly distinctive according to the PERMANOVA test (R2 = 0.132, P = 0.001), and the alpha-diversity was significantly lower in CRC. Beta-diversity, based on principal coordinate analysis, showed a distinct taxonomy between the CRC and the healthy.
Levels of Pseudomonadota, Escherichia, Citrobacter freundii, Klebsiella sp. LTGPAF-6F, Escherichia albertii, Escherichia coli, Caudovirales, Apicomplexa, and Verrucomicrobiota populations were significantly elevated in CRC. The major metabolic pathways with higher relative abundance levels found in CRC compared to healthy were related to HEMESYN2-PWY: heme biosynthesis II (anaerobic), PWY-5154:L-arginine biosynthesis III (via N-acetyl-L-citrulline), FUC-RHAMCAT-PWY: superpathway of fucose and rhamnose degradation, ECASYN-PWY: enterobacterial common antigen biosynthesis, ENTBACSYN-PWY: enterobactin biosynthesis, and AEROBACTINSYN-PWY: aerobactin biosynthesis.
Conclusion
Distinct gut microbiome profiles between healthy and CRC were observed. In particular, the findings showed a significant reduction in microbial diversity in stage III CRC. This study provides initial metagenomic data on Malian patients with CRC. It will be used to create a larger cohort to better understand the relationship between CRC and the gut microbiota in the Malian CRC population.
{"title":"Characterization of the gut microbiota in patients with stage III colorectal cancer: A case-control study","authors":"Mahamane T. Diakité , Shan Sun , Anou M. Somboro , Brehima Diakité , Amadou Koné , Yaya Kassogué , Djeneba Fofana , Saidou Balam , Cheick B Traoré , Aminata Maiga , Bakarou Kamaté , Djibril Ba , Modibo Diarra , Soungou Boré , Almoustapha I. Maiga , Qi Dai , Drew Robert Nannini , Jane Holl , Robert Murphy , Lifang Hou , Mamoudou Maiga","doi":"10.1016/j.gene.2025.149913","DOIUrl":"10.1016/j.gene.2025.149913","url":null,"abstract":"<div><h3>Aim</h3><div>To conduct a case-control study (pilot study) in Africa (Mali) in comparing the gut microbiota of patients with stage III colorectal cancer (CRC) using next-generation sequencing.</div></div><div><h3>Methods</h3><div>Shotgun sequencing was performed to characterize participants’ fecal microbiota using Illumina’s HiSeq platform. This case-control study involved newly diagnosed CRC patients (n = 23) prior to any treatment initiation, and unrelated healthy controls (n = 24) to elucidate their microbial diversity and relative abundance.</div></div><div><h3>Results</h3><div>The findings revealed that the gut microbiota in CRC and in healthy were significantly distinctive according to the PERMANOVA test (R<sup>2</sup> = 0.132, P = 0.001), and the alpha-diversity was significantly lower in CRC. Beta-diversity, based on principal coordinate analysis, showed a distinct taxonomy between the CRC and the healthy.</div><div>Levels of <em>Pseudomonadota</em>, <em>Escherichia</em>, <em>Citrobacter freundii</em>, <em>Klebsiella</em> sp. <em>LTGPAF-6F</em>, <em>Escherichia albertii, Escherichia coli, Caudovirales</em>, <em>Apicomplexa,</em> and <em>Verrucomicrobiota</em> populations were significantly elevated in CRC. The major metabolic pathways with higher relative abundance levels found in CRC compared to healthy were related to <em>HEMESYN2-PWY: heme biosynthesis II (anaerobic)</em>, <em>PWY-5154:L-arginine biosynthesis III (via N-acetyl-L-citrulline)</em>, <em>FUC-RHAMCAT-PWY: superpathway of fucose and rhamnose degradation</em>, <em>ECASYN-PWY: enterobacterial common antigen biosynthesis, ENTBACSYN-PWY: enterobactin biosynthesis,</em> and <em>AEROBACTINSYN-PWY: aerobactin biosynthesis.</em></div></div><div><h3>Conclusion</h3><div>Distinct gut microbiome profiles between healthy and CRC were observed. In particular, the findings showed a significant reduction in microbial diversity in stage III CRC. This study provides initial metagenomic data on Malian patients with CRC. It will be used to create a larger cohort to better understand the relationship between CRC and the gut microbiota in the Malian CRC population.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149913"},"PeriodicalIF":2.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ecDNA is a circular DNA extensively present in human cancers, particularly advanced tumors, but rarely detected in healthy cells. Previously, they were named “minute chromatin bodies,” which eventually changed into “Double minutes (DMs)” as they exist in pairs. Due to their structural and epigenetic modifications, they confer specific advantages, helping them to survive and persist within cells. Rapid amplification of drug-resistant genes or oncogenes, increased chromatin accessibility, and non-Mendelian inheritance all contribute significantly to tumor adaptability, aggressiveness, and resistance to drug or chemotherapy treatment. Thus, this review paper aims to discuss DMs’ formation, mechanism, and maintenance, examining the tools used to detect them and investigating the commonly observed oncogenes in different cancer types. Lastly, the therapeutic approaches applied over the years have been to reduce or eliminate DMs in tumor cells.
{"title":"Double minutes: exploring the formation and oncogenic roles in cancer progression","authors":"Mahjabin Sanam, Chowdhury Fatema Tuz Zohra Hossain, Jahin Fairuj Oishi, Reasat Tarannum, Nusrat Zahan Rouf","doi":"10.1016/j.gene.2025.149879","DOIUrl":"10.1016/j.gene.2025.149879","url":null,"abstract":"<div><div>ecDNA is a circular DNA extensively present in human cancers, particularly advanced tumors, but rarely detected in healthy cells. Previously, they were named “minute chromatin bodies,” which eventually changed into “Double minutes (DMs)” as they exist in pairs. Due to their structural and epigenetic modifications, they confer specific advantages, helping them to survive and persist within cells. Rapid amplification of drug-resistant genes or oncogenes, increased chromatin accessibility, and non-Mendelian inheritance all contribute significantly to tumor adaptability, aggressiveness, and resistance to drug or chemotherapy treatment. Thus, this review paper aims to discuss DMs’ formation, mechanism, and maintenance, examining the tools used to detect them and investigating the commonly observed oncogenes in different cancer types. Lastly, the therapeutic approaches applied over the years have been to reduce or eliminate DMs in tumor cells.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149879"},"PeriodicalIF":2.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145487869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05Epub Date: 2025-11-20DOI: 10.1016/j.gene.2025.149910
Lilian de Sá Garcia Landeiro , Pedro Augusto Silva dos Santos Rodrigues , Almirane Lima de Oliveira , Katarina Mattos Brandão , Laryssa Cardoso Calmon , João Victor Andrade Cruz , Mailane dos Anjos Silva , Bruna Ramos Tosta , Ingrid de Marins de Almeida , João Locke Ferreira de Araújo , Thamara Miranda Barbosa dos Santos , Milca de Jesus Silva , Gabriela Pimentel Pinheiro das Chagas , Álvaro Augusto Souza da Cruz Filho , Camila Alexandrina Viana de Figueirêdo , Pablo de Moura Santos , Ryan dos Santos Costa
Objective
Rheumatoid arthritis (RA) is a chronic inflammatory disease that can lead to progressive disability. TNF inhibitors (TNFi) have shown promise in improving disease progression and prognosis; however, only 60% to 70% of patients respond well. Genetic variations have been linked to this therapeutic failure. Genetic variants in the IL17 gene are associated with TNFi therapy responses and RA susceptibility, but few studies have explored this in the Brazilian population. This study assesses variants in the IL-17 pathway (rs763780, rs2275913, rs3819024) in RA patients undergoing TNFi treatment in Salvador, BA. Methods: A total of 497 individuals (294 RA patients, 203 healthy controls) were included. Plasma levels of IL-17, IL-1β, TNF, and other cytokines were measured in a subpopulation. Meta-analysis of published studies was conducted to consolidate associations between IL and 17 variants and RA susceptibility. Results: No significant associations were found between SNVs and RA susceptibility in the cohort, while the meta-analysis revealed protective and risk associations. The rs3819024-G allele was associated with improved TNFi response, particularly in infliximab users, whereas rs2275913-AA carriers had higher risk of treatment.
{"title":"IL17 genetic variants impact the response and safety of TNFi treatment in rheumatoid arthritis patients from Bahia, Brazil","authors":"Lilian de Sá Garcia Landeiro , Pedro Augusto Silva dos Santos Rodrigues , Almirane Lima de Oliveira , Katarina Mattos Brandão , Laryssa Cardoso Calmon , João Victor Andrade Cruz , Mailane dos Anjos Silva , Bruna Ramos Tosta , Ingrid de Marins de Almeida , João Locke Ferreira de Araújo , Thamara Miranda Barbosa dos Santos , Milca de Jesus Silva , Gabriela Pimentel Pinheiro das Chagas , Álvaro Augusto Souza da Cruz Filho , Camila Alexandrina Viana de Figueirêdo , Pablo de Moura Santos , Ryan dos Santos Costa","doi":"10.1016/j.gene.2025.149910","DOIUrl":"10.1016/j.gene.2025.149910","url":null,"abstract":"<div><h3>Objective</h3><div>Rheumatoid arthritis (RA) is a chronic inflammatory disease that can lead to progressive disability. TNF inhibitors (TNFi) have shown promise in improving disease progression and prognosis; however, only 60% to 70% of patients respond well. Genetic variations have been linked to this therapeutic failure. Genetic variants in the IL17 gene are associated with TNFi therapy responses and RA susceptibility, but few studies have explored this in the Brazilian population. This study assesses variants in the IL-17 pathway (rs763780, rs2275913, rs3819024) in RA patients undergoing TNFi treatment in Salvador, BA. Methods: A total of 497 individuals (294 RA patients, 203 healthy controls) were included. Plasma levels of IL-17, IL-1β, TNF, and other cytokines were measured in a subpopulation. Meta-analysis of published studies was conducted to consolidate associations between IL and 17 variants and RA susceptibility. Results: No significant associations were found between SNVs and RA susceptibility in the cohort, while the <em>meta</em>-analysis revealed protective and risk associations. The rs3819024-G allele was associated with improved TNFi response, particularly in infliximab users, whereas rs2275913-AA carriers had higher risk of treatment.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149910"},"PeriodicalIF":2.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05Epub Date: 2025-11-10DOI: 10.1016/j.gene.2025.149877
Xiangzhen Gou , Keyan Ma , Junxiang Yang , Ke Wang , Yuqin Ma
China harbors rich indigenous goat resources. However, factors such as the introduction of exotic breeds and crossbreeding have led to a decline in local populations and obscured genetic structures. Consequently, it is imperative to conduct genetic diversity and population structure assessments of key indigenous goat populations. This study employed Super-GBS sequencing technology to evaluate genetic diversity and population structure in eight goat breeds (n = 211), and further identified candidate genes associated with production traits and environmental adaptation through selection signature analysis. Ziwuling black goat (ZWL) exhibited the highest diversity, whereas Dazu black goat (DZH) showed the lowest. Pairwise FST revealed strong differentiation between DZH and Liaoning cashmere / Inner Mongolia cashmere goat (NMC) (0.1221) due to geographic isolation, but negligible divergence between Ziwuling cashmere (ZWLH) and Hexi cashmere (HXC) (0.0066), indicating gene flow. Population structure resolved three clades: DZH as an independent lineage, Yimeng black goat (YMH) clustering with ZWL, and multiple cashmere subgroups. Runs of homozygosity (ROH) revealed elevated inbreeding in DZH (FROH = 0.178) versus lower levels in cashmere breeds (0.071–0.098). Selective sweeps identified 252 genes linked to cashmere traits, including DCN, SEMA3D, FGF5, enriched in TGF-β, MAPK, and circadian rhythm pathways regulating hair follicle cycling. Comparative scans between arid-adapted NMC and subtropical DZH identified 372 genes (e.g., MTOR, ROBO2, PPP3CA) involved in thermogenesis, water reabsorption, and hypoxia response. Together, these findings highlight how artificial selection and environmental adaptation jointly shape goat genomic architecture. Conservation should prioritize populations with declining diversity (e.g., ZWLH, SXC) and implement controlled breeding to reduce inbreeding, thereby safeguarding agro-biodiversity and sustainable utilization.
{"title":"Population structure analysis of eight goat breeds based on super-genotyping-by-sequencing","authors":"Xiangzhen Gou , Keyan Ma , Junxiang Yang , Ke Wang , Yuqin Ma","doi":"10.1016/j.gene.2025.149877","DOIUrl":"10.1016/j.gene.2025.149877","url":null,"abstract":"<div><div>China harbors rich indigenous goat resources. However, factors such as the introduction of exotic breeds and crossbreeding have led to a decline in local populations and obscured genetic structures. Consequently, it is imperative to conduct genetic diversity and population structure assessments of key indigenous goat populations. This study employed Super-GBS sequencing technology to evaluate genetic diversity and population structure in eight goat breeds (n = 211), and further identified candidate genes associated with production traits and environmental adaptation through selection signature analysis. Ziwuling black goat (ZWL) exhibited the highest diversity, whereas Dazu black goat (DZH) showed the lowest. Pairwise <em>F</em><sub>ST</sub> revealed strong differentiation between DZH and Liaoning cashmere / Inner Mongolia cashmere goat (NMC) (0.1221) due to geographic isolation, but negligible divergence between Ziwuling cashmere (ZWLH) and Hexi cashmere (HXC) (0.0066), indicating gene flow. Population structure resolved three clades: DZH as an independent lineage, Yimeng black goat (YMH) clustering with ZWL, and multiple cashmere subgroups. Runs of homozygosity (ROH) revealed elevated inbreeding in DZH (F<sub>ROH</sub> = 0.178) versus lower levels in cashmere breeds (0.071–0.098). Selective sweeps identified 252 genes linked to cashmere traits, including <em>DCN</em>, <em>SEMA3D</em>, <em>FGF5</em>, enriched in TGF-β, MAPK, and circadian rhythm pathways regulating hair follicle cycling. Comparative scans between arid-adapted NMC and subtropical DZH identified 372 genes (e.g., <em>MTOR</em>, <em>ROBO2</em>, <em>PPP3CA</em>) involved in thermogenesis, water reabsorption, and hypoxia response. Together, these findings highlight how artificial selection and environmental adaptation jointly shape goat genomic architecture. Conservation should prioritize populations with declining diversity (e.g., ZWLH, SXC) and implement controlled breeding to reduce inbreeding, thereby safeguarding agro-biodiversity and sustainable utilization.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149877"},"PeriodicalIF":2.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05Epub Date: 2025-11-06DOI: 10.1016/j.gene.2025.149880
Mengna Zhang , Jianfei Lin , Shijian Liu , Yanrui Jiang , Min Meng , Qi Zhu , Guanghai Wang , Fan Jiang , Hao Mei
Objective
This study assesses the influence of genetic variations over 9 genes (FTO, CLOCK, ARNTL, CRP, IL6, NR3C1, LEP, GHRL, and ADIPOQ) involved in energy homeostasis and stress regulation on children’s anthropometric traits and examines the impact of sleep duration on these genetic associations.
Methods
We analyzed 255 preschool children from Shanghai, China, and sequenced genetic variants from the nine candidate genes. Three genetic risk scores (GRS) were derived: GRSall, derived from all filtered SNPs; GRSBMI, based on three SNPs identified in a BMI GWAS reference; and uGRS5 constructed from locally identified SNPs. Linear regression and Firth’s logistic regression were applied to assess GRS effects, and stratified analyses were performed to evaluate sleep impact on GRS associations.
Results
After adjusting for age, sex, and appetite with FDR correction, GRSall showed marginal associations with several anthropometric measures; GRSBMI demonstrated stronger associations with more anthropometric traits and smaller p-values; and uGRS5 exhibited the strongest associations overall. Stratified analyses showed that GRS associations were evident only in children with adequate sleep, while the associations were absent in the short sleep group.
Conclusions
Our findings suggest that genetic variants in the nine candidate genes, particularly those from FTO, LEP and GHRL, exert cumulative effects on anthropometric traits. GRS constructed from SNPs with modest effects can serve as a predictive tool for anthropometric outcomes and obesity risk, while GRS based on GWAS-identified SNPs can offer greater predictive power than GRS based on all eligible SNPs. Importantly, adequate sleep is essential for the manifestation of these genetic effects, whereas insufficient sleep may attenuate or mask them. These results highlight the importance of incorporating sleep as a key environmental factor in genetic studies and support personalized strategies for managing obesity risk in children.
{"title":"Influence of sleep duration on cumulative genetic effects on obesity and related anthropometric traits among preschool children","authors":"Mengna Zhang , Jianfei Lin , Shijian Liu , Yanrui Jiang , Min Meng , Qi Zhu , Guanghai Wang , Fan Jiang , Hao Mei","doi":"10.1016/j.gene.2025.149880","DOIUrl":"10.1016/j.gene.2025.149880","url":null,"abstract":"<div><h3>Objective</h3><div>This study assesses the influence of genetic variations over 9 genes (<em>FTO, CLOCK, ARNTL, CRP, IL6, NR3C1, LEP, GHRL</em>, and <em>ADIPOQ</em>) involved in energy homeostasis and stress regulation on children’s anthropometric traits and examines the impact of sleep duration on these genetic associations.</div></div><div><h3>Methods</h3><div>We analyzed 255 preschool children from Shanghai, China, and sequenced genetic variants from the nine candidate genes. Three genetic risk scores (GRS) were derived: GRS<sub>all</sub>, derived from all filtered SNPs; GRS<sub>BMI</sub>, based on three SNPs identified in a BMI GWAS reference; and uGRS<sub>5</sub> constructed from locally identified SNPs. Linear regression and Firth’s logistic regression were applied to assess GRS effects, and stratified analyses were performed to evaluate sleep impact on GRS associations.</div></div><div><h3>Results</h3><div>After adjusting for age, sex, and appetite with FDR correction, GRS<sub>all</sub> showed marginal associations with several anthropometric measures; GRS<sub>BMI</sub> demonstrated stronger associations with more anthropometric traits and smaller p-values; and uGRS<sub>5</sub> exhibited the strongest associations overall. Stratified analyses showed that GRS associations were evident only in children with adequate sleep, while the associations were absent in the short sleep group.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that genetic variants in the nine candidate genes, particularly those from <em>FTO</em>, <em>LEP</em> and <em>GHRL</em>, exert cumulative effects on anthropometric traits. GRS constructed from SNPs with modest effects can serve as a predictive tool for anthropometric outcomes and obesity risk, while GRS based on GWAS-identified SNPs can offer greater predictive power than GRS based on all eligible SNPs. Importantly, adequate sleep is essential for the manifestation of these genetic effects, whereas insufficient sleep may attenuate or mask them. These results highlight the importance of incorporating sleep as a key environmental factor in genetic studies and support personalized strategies for managing obesity risk in children.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149880"},"PeriodicalIF":2.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05Epub Date: 2025-10-16DOI: 10.1016/j.gene.2025.149838
Ting Wang , Jiaqi Wang , Yumei Jiang , Zhiheng Liang , Peipei Zhang , Qi Wang , Ying Xue , Yutao Wu , Qiaoyun Li , Zengjun Qi , Jishan Niu
Spike development in wheat (Triticum aestivum L.) is crucial in determining spike type, which affects agronomic traits, such as spikelet number, grain shape, kilo-grain-weight, and ultimately affects wheat yield. Therefore, it is valuable for wheat genetic studies and breeding to mine the genes involved in spike development. A small spikelet and compact glume mutant 1 (sscg1) was obtained from wheat line Shengnong 1 treated with ethyl methane sulfonate (EMS). The typical characteristics of the mutant sscg1 were its smaller spikelets and compacted glumes. In this study, the agronomy traits, karyotype, heredity, and mutated gene mapping of sscg1 were systemically studied. The mutant traits were controlled by a recessive gene named as sscg1, which was fine mapped in a 1.33 Mb region covering 147.28–148.61 Mb on chromosome 3AS in CS1.0. Seven putative candidate genes were identified in this region. Because no spike developmental related genes have been reported in this region, sscg1 was a novel spike development regulation gene. Considered the annotated functions and expression levels of the candidate genes, IAA3-3A encoded an auxin-responsive IAA3-like protein in CS2.1, and almost didn’t express in mutant sscg1 during spike development, it most likely was the mutated gene. Transcriptome sequencing, qRT-PCR and determination of the endogenous hormone IAA contents demonstrated that the expressions of most TaARF genes were significantly increased, and the IAA contents were decreased during spike development in sscg1. The result suggested that the IAA signal pathway was a key factor controlling wheat spike development. Using elite alleles of IAA3-3A and regulating IAA signal pathway can be an approach for wheat yield breeding.
{"title":"Heredity and gene fine mapping of a small spikelet and compact glume 1 (sscg1) mutant in wheat","authors":"Ting Wang , Jiaqi Wang , Yumei Jiang , Zhiheng Liang , Peipei Zhang , Qi Wang , Ying Xue , Yutao Wu , Qiaoyun Li , Zengjun Qi , Jishan Niu","doi":"10.1016/j.gene.2025.149838","DOIUrl":"10.1016/j.gene.2025.149838","url":null,"abstract":"<div><div>Spike development in wheat (<em>Triticum aestivum</em> L.) is crucial in determining spike type, which affects agronomic traits, such as spikelet number, grain shape, kilo-grain-weight, and ultimately affects wheat yield. Therefore, it is valuable for wheat genetic studies and breeding to mine the genes involved in spike development. A small spikelet and compact glume mutant 1 (<em>sscg1</em>) was obtained from wheat line Shengnong 1 treated with ethyl methane sulfonate (EMS). The typical characteristics of the mutant <em>sscg1</em> were its smaller spikelets and compacted glumes. In this study, the agronomy traits, karyotype, heredity, and mutated gene mapping of <em>sscg1</em> were systemically studied. The mutant traits were controlled by a recessive gene named as <em>sscg1</em>, which was fine mapped in a 1.33 Mb region covering 147.28–148.61 Mb on chromosome 3AS in CS1.0. Seven putative candidate genes were identified in this region. Because no spike developmental related genes have been reported in this region, <em>sscg1</em> was a novel spike development regulation gene. Considered the annotated functions and expression levels of the candidate genes, <em>IAA3-3A</em> encoded an auxin-responsive IAA3-like protein in CS2.1, and almost didn’t express in mutant <em>sscg1</em> during spike development, it most likely was the mutated gene. Transcriptome sequencing, qRT-PCR and determination of the endogenous hormone IAA contents demonstrated that the expressions of most <em>TaARF</em> genes were significantly increased, and the IAA contents were decreased during spike development in <em>sscg1.</em> The result suggested that the IAA signal pathway was a key factor controlling wheat spike development. Using elite alleles of <em>IAA3-3A</em> and regulating IAA signal pathway can be an approach for wheat yield breeding.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149838"},"PeriodicalIF":2.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号