Human Genetics最新文献_第4页

A novel pathogenic synonymous DHCR7 variant unveiled by aberrant splicing in Smith-Lemli-Opitz syndrome. Smith-Lemli-Opitz综合征异常剪接揭示了一种新的病原同源DHCR7变异。

IF 3.4 2区生物学

Human Genetics Pub Date : 2026-07-06 DOI: 10.1007/s00439-026-02853-2

Yan Zhou, Qin Zhang, Quanze He, Guohua Yang, Haibo Li, Yu An

{"title":"A novel pathogenic synonymous DHCR7 variant unveiled by aberrant splicing in Smith-Lemli-Opitz syndrome.","authors":"Yan Zhou, Qin Zhang, Quanze He, Guohua Yang, Haibo Li, Yu An","doi":"10.1007/s00439-026-02853-2","DOIUrl":"10.1007/s00439-026-02853-2","url":null,"abstract":"Synonymous mutations, once regarded as silent, are increasingly recognized as pathogenic through disruption of mRNA splicing. Here, we report a prenatal case with classic features of Smith-Lemli-Opitz syndrome (SLOS), including increased nuchal translucency, enlarged kidneys, and fetal growth restriction. Whole-exome sequencing identified compound heterozygous DHCR7 variants: a previously reported missense variant, NM_001360.3:c.1220A > G (p.Asn407Ser), and a novel synonymous variant, NM_001360.3:c.963G > A (p.Gln321 =). Functional validation using minigene assays and patient-derived cDNA demonstrated that c.963G > A causes aberrant splicing, resulting in a premature termination codon and production of a truncated protein lacking the sterol-sensing domain, which contains multiple recurrent pathogenic missense sites. These findings establish the deleterious effect of this synonymous change, analogous to the well-characterized splice-site variant NM_001360.3:c.964 - 1G > C (historically referred to as IVS8 - 1G > C). In sum, this study provides the first definitive evidence that a synonymous DHCR7 variant can act as a likely pathogenic allele through splicing disruption. Moreover, it offers critical molecular insight and a refined framework for interpreting synonymous variants-particularly variants of uncertain significance-with important implications for clinical diagnosis, genetic counseling, and prenatal care.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blending borders: reconstructing the genetic history of the Sindhi population. 混合边界：重建信德人口的遗传历史。

IF 3.4 2区生物学

Human Genetics Pub Date : 2026-07-06 DOI: 10.1007/s00439-026-02851-4

Chanchal Devnani, Khushboo Gautam, Rakesh Rawal, Gyaneshwer Chaubey

{"title":"Blending borders: reconstructing the genetic history of the Sindhi population.","authors":"Chanchal Devnani, Khushboo Gautam, Rakesh Rawal, Gyaneshwer Chaubey","doi":"10.1007/s00439-026-02851-4","DOIUrl":"10.1007/s00439-026-02851-4","url":null,"abstract":"Sindhis are an Indo-Aryan ethnolinguistic community primarily associated with the Sindh region of present-day Pakistan. The Sindhi community is celebrated for its vibrant culture, unique dialect, and notable accomplishments in commerce and the arts, reflecting a rich historical legacy. Following the partition of India in 1947, many Sindhis migrated from the Sindh region to India and around the world, establishing diaspora communities. Previous genetic studies on Sindhis have focused on those residing in Pakistan, with a notable lack of genome-wide research specifically addressing Indian Sindhis. In this study, we investigated the demographic history of Sindhi populations across India and Pakistan by analysing hundreds of thousands of biallelic markers from 113 Indian Sindhi individuals, alongside existing data from Pakistani Sindhis. Our allele frequency analysis revealed strong genetic connections between Sindhi populations in Pakistan and India. Haplotype-based assessments further confirmed recent shared ancestry between these groups and highlighted genetic similarities with neighbouring populations. Identity-by-descent (IBD) analyses reinforced the close genetic relationships between Indian and Pakistani Sindhis, as well as their ties to nearby Pakistani groups. Interestingly, analysis of Runs of Homozygosity (RoH) revealed distinct patterns of marriage practices, suggesting that Pakistani Sindhis exhibit higher homozygosity, likely due to the prevalence of consanguineous marriages. Additionally, local ancestry analysis identified a dominant ancestral component associated with modern populations of the Indus Valley region. The results illuminate the complex genetic structure of the Sapta-Sindhu region and trace the origins of Sindhi Diaspora communities back to the ancient region of Sindh.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A genetic variant of adenylate cyclase 7 associated with ulcerative colitis shows impaired function and G-protein-coupled receptor signaling. 与溃疡性结肠炎相关的腺苷酸环化酶7的遗传变异显示功能受损和g蛋白偶联受体信号传导。

IF 3.4 2区生物学

Human Genetics Pub Date : 2026-07-04 DOI: 10.1007/s00439-026-02848-z

Gabriele Loers, Selen Cangüzel, Sebastian Rading, Christian Kubisch, Meliha Karsak

{"title":"A genetic variant of adenylate cyclase 7 associated with ulcerative colitis shows impaired function and G-protein-coupled receptor signaling.","authors":"Gabriele Loers, Selen Cangüzel, Sebastian Rading, Christian Kubisch, Meliha Karsak","doi":"10.1007/s00439-026-02848-z","DOIUrl":"10.1007/s00439-026-02848-z","url":null,"abstract":"A missense variant of adenylate cyclase 7 (AC7), p.Asp439Glu, has been significantly associated with ulcerative colitis (UC) in genome-wide association studies. Previous work suggested that this variant is reduced in expression and exhibits impaired cyclic adenosine-3',5'-monophosphate (cAMP) synthesis, thus skewing T-cell cytokine profiles. Here, we investigated the variant's function measuring dynamic cAMP responses in live HEK293 cells. We show that p.Asp439Glu generates significantly reduced basal cAMP levels despite normal expression. Stimulation with sphingosine-1-phosphate (S1P) and phorbol 12-myristate 13-acetate (PMA) induced a reduced cAMP increase in cells expressing mutant AC7, indicating reduced responsiveness to G-protein-coupled receptor (GPCR) and protein kinase C (PKC) activation. Western blot analysis showed altered downstream phosphorylation of cAMP response element-binding protein (CREB) and cAMP-dependent transcription factor (ATF1) in cells expressing the variant. Higher levels of phosphorylated CREB and ATF1 were observed in cells expressing p.Asp439Glu AC7 under basal conditions while stimulation with S1P had no effect on protein phosphorylation. Our findings provide direct biochemical evidence for strongly impaired AC7 function caused by the variant p.Asp439Glu. These results may pave the way for more causally defined and genotype-specific treatment strategies in UC.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Within-sibling attenuation of polygenic risk score accuracy: investigating the effects of principal component analysis, LD score regression, and mixed model association in the UK Biobank. 兄弟姐妹间多基因风险评分准确性的衰减：调查英国生物银行主成分分析、LD评分回归和混合模型关联的影响。

IF 3.4 2区生物学

Human Genetics Pub Date : 2026-07-04 DOI: 10.1007/s00439-026-02852-3

Ciaran Michael Kelly, Onyedika Onuorah, Edmund Gilbert

{"title":"Within-sibling attenuation of polygenic risk score accuracy: investigating the effects of principal component analysis, LD score regression, and mixed model association in the UK Biobank.","authors":"Ciaran Michael Kelly, Onyedika Onuorah, Edmund Gilbert","doi":"10.1007/s00439-026-02852-3","DOIUrl":"10.1007/s00439-026-02852-3","url":null,"abstract":"A central challenge in polygenic risk prediction is measuring and controlling for confounding due to population stratification. Standard approaches include adjusting for leading principal components (PCs) of genetic variation and using linear mixed models in genome-wide association studies (GWAS). Evidence of adequate control is typically inferred from reductions in the linkage disequilibrium score regression (LDSC) intercept and the preservation of polygenic risk score (PRS) performance in within-sibling settings. Here, we investigate how the number of PCs included during GWAS/PRS construction relates to the loss of predictive performance when moving from population-based analyses to that of discordant sibling pairs (within-sibling attenuation). This design detects confounding arising from environmental and genetic background effects correlated with population structure. Analyses were performed in the self-identified White subset of the UK Biobank (UKB) for coronary artery disease, type 2 diabetes, breast cancer, and prostate cancer, with educational attainment included as a comparison trait as it is known to exhibit substantial within-sibling attenuation. We find that increasing the number of PCs does not consistently reduce within-sibling attenuation across traits. Furthermore, reductions in attenuation do not closely correspond to decreases in the LDSC intercept, and mixed model-based methods offer little additional improvement in prediction or attenuation. Overall, our results suggest that confounding targeted by PC-adjustment and linear mixed models is either minimal in the UKB, or remains inadequately captured by current methods, reflecting limitations as to how much standard population structure correction improves the causal validity of PRS in the UKB.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long-read genome sequencing resolves a de novo complex 18q12.1q21.2 triplication causing partial tetrasomy and reveals its underlying mechanism. 长读基因组测序解决了导致部分四体病的一个新生复合体18q12.1q21.2三倍，并揭示了其潜在机制。

IF 3.4 2区生物学

Human Genetics Pub Date : 2026-07-04 DOI: 10.1007/s00439-026-02855-0

Serena Redaelli, Viviana Tritto, Eleonora Mangano, Roberta Bordoni, Elena Sala, Nicoletta Villa, Francesca Crosti, Leda Dalprà, Luigina Spaccini, Alessandra Sirtori, Giovanni Cazzaniga, Donatella Conconi, Angela Bentivegna, Paola Riva

{"title":"Long-read genome sequencing resolves a de novo complex 18q12.1q21.2 triplication causing partial tetrasomy and reveals its underlying mechanism.","authors":"Serena Redaelli, Viviana Tritto, Eleonora Mangano, Roberta Bordoni, Elena Sala, Nicoletta Villa, Francesca Crosti, Leda Dalprà, Luigina Spaccini, Alessandra Sirtori, Giovanni Cazzaniga, Donatella Conconi, Angela Bentivegna, Paola Riva","doi":"10.1007/s00439-026-02855-0","DOIUrl":"10.1007/s00439-026-02855-0","url":null,"abstract":"Chromosomal triplications are rare structural variations often associated with complex phenotypes. We report the molecular characterization of a novel intrachromosomal triplication at 18q12.1q21.2 identified in a fetus with ultrasound abnormalities. Conventional karyotyping and array-CGH revealed a partial tetrasomy and a 26 Mb region of loss of homozygosity (LOH), extending from the triplication to the telomere. Long-read sequencing (LRS) identified breakpoint junctions revealing a direct-inverted-direct triplication structure. Breakpoint analysis suggested that this rearrangement arose through a U-type exchange between sister chromatids, likely mediated by microhomology-based mechanisms. This process likely generated a transient dicentric chromosome that subsequently broke during mitosis. The resulting duplicated chromosome may have been stabilized by telomere capture, consistent with the triplicated 18q12.1q21.2 region followed by the 18q21.2q23 LOH. Nine genes within the triplicated region, including SMAD2 and SMAD4, showed high predicted sensitivity to increased dosage, possibly contributing to the clinical phenotype. This study highlights the utility of LRS in defining complex chromosomal rearrangements and emphasizes the importance of molecular breakpoint analysis for understanding pathogenic mechanisms and improving genetic prenatal diagnosis.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AI in variant analysis: fast track to genetic diagnoses. 变异分析中的人工智能：基因诊断的快速通道。

IF 3.4 2区生物学

Human Genetics Pub Date : 2026-06-26 DOI: 10.1007/s00439-026-02847-0

Elizabeth J Wilk, Sasha Taluri, Timothy C Howton, Anthony B Crumley, Michal Mrug, Brittany N Lasseigne

{"title":"AI in variant analysis: fast track to genetic diagnoses.","authors":"Elizabeth J Wilk, Sasha Taluri, Timothy C Howton, Anthony B Crumley, Michal Mrug, Brittany N Lasseigne","doi":"10.1007/s00439-026-02847-0","DOIUrl":"10.1007/s00439-026-02847-0","url":null,"abstract":"While falling costs have expanded access to genomic sequencing, clinical utility is frequently hindered by the challenge of interpreting complex genetic data. Variant analysis for rare disease patients especially requires significant time and expertise, creating a bottleneck that delays diagnostics. Although advances in genetic variant classification have improved diagnostic precision, they have also increased the identification of variants of uncertain significance (VUSs), widening the interpretation gap between data generation and clinical actionability. The high prevalence of VUSs can lead to false reassurance or psychological distress by misinterpretting inconclusive results. We propose that artificial intelligence (AI) is a critical clinical decision-support tool for bridging this gap, offering a scalable framework to optimize variant interpretation and shorten the diagnostic odyssey. While reclassification ultimately requires biological evidence that AI cannot replace, these tools serve as essential aggregators and prioritizers, especially as guidelines transition toward the upcoming quantitative ACMG v4 framework. We advocate integrating AI throughout the genetic diagnostic workflow-from initial phenotyping to variant prioritization-to facilitate data-driven, personalized treatment. We outline current AI-assisted approaches and discuss anticipated challenges in this pursuit, such as privacy, training data bias and quality, model explainability, and the necessity of a total product life cycle for validation. To address these challenges, we provide recommendations for \"human-in-the-loop\" design and intuitive workflow integration to ensure AI tools meet the highest standards of precision, reproducibility, and transparency to maximize adoption. By standardizing AI across the variant analysis pipeline, we can fast-track the path to genetic diagnoses, effectively bridging the interpretation gap and enabling rapid delivery of personalized medical interventions.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combined family-based association and linkage analyses in families affected by attention-deficit hyperactivity disorder. 注意缺陷多动障碍家庭的关联与连锁分析。

IF 3.4 2区生物学

Human Genetics Pub Date : 2026-06-22 DOI: 10.1007/s00439-026-02840-7

Cristina M Justice, Kwangmi Ahn, Benjamin Jung, Luke J Norman, Gustavo Sudre, Wendy Sharp, Marine Bouyssi-Kobar, Saadia Choudhury, Stevi Gligorovic, Paul Kundzicz, Maria T Acosta, Philip Shaw

{"title":"Combined family-based association and linkage analyses in families affected by attention-deficit hyperactivity disorder.","authors":"Cristina M Justice, Kwangmi Ahn, Benjamin Jung, Luke J Norman, Gustavo Sudre, Wendy Sharp, Marine Bouyssi-Kobar, Saadia Choudhury, Stevi Gligorovic, Paul Kundzicz, Maria T Acosta, Philip Shaw","doi":"10.1007/s00439-026-02840-7","DOIUrl":"10.1007/s00439-026-02840-7","url":null,"abstract":"Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent and heritable of neurodevelopmental disorders. To characterize the genetic variants contributing to this heritability, we studied families with members affected by ADHD. Genome-wide array data were obtained on two cohorts: NHGRI Family Cohort (359 nuclear families,1538 individuals) and NCR Family Cohort (25 multigenerational and 132 nuclear families, 631 members). A meta-analysis of family-based association tests (FBAT) of the two cohorts identified three genome-wide significant associations, one upstream from TFRC, and two that were intronic to GSDME and to TRIM31, with the last gene previously implicated in ADHD. Genes associated with ADHD (MAGMA, gene-based association P < 0.05) overlapped with genes implicated in ADHD by prior case/control genome-wide association studies. Meta-analyses of the linkage signals identified one significant linkage region (LOD > 3) on 19p13.2-13.11 that encompassed a genome-wide significant variant in the FBAT of the NHGRI Family Cohort (rs55741253, P = 2.68 × 10- 8). Additionally, two of the five linkage regions that reached a LOD > 2 in our meta-analysis replicated significant linkages from prior studies (prior studies reporting 13 linkages with LOD > 3.0; hypergeometric test of overlapping linkage signals, P < 0.01). Using neuroimaging data from the NCR cohort, we found genes associated with ADHD overlapped with genes associated with the brain's total surface area and a feature of functional connectivity, reflecting the interaction between the brain's default mode and task positive networks. Such work begins to delineate the neural substrates of the discovered genetic associations with familial ADHD.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating the shared genetic architecture between selective immunoglobulin A deficiency and autoimmune diseases. 选择性免疫球蛋白A缺乏症与自身免疫性疾病之间的共同遗传结构研究。

IF 3.4 2区生物学

Human Genetics Pub Date : 2026-06-22 DOI: 10.1007/s00439-026-02850-5

Xiao Dang, Frank Qingyun Wang, Caicai Zhang, Huidong Su, Yao Lei, Jing Yang, Yu Lung Lau, Wanling Yang

{"title":"Investigating the shared genetic architecture between selective immunoglobulin A deficiency and autoimmune diseases.","authors":"Xiao Dang, Frank Qingyun Wang, Caicai Zhang, Huidong Su, Yao Lei, Jing Yang, Yu Lung Lau, Wanling Yang","doi":"10.1007/s00439-026-02850-5","DOIUrl":"10.1007/s00439-026-02850-5","url":null,"abstract":"Selective immunoglobulin A deficiency (IgAD) is the most prevalent primary immunodeficiency and frequently coexists with autoimmune diseases (ADs), suggesting a shared genetic etiology. While genome-wide association studies (GWAS) have identified only a few risk loci for IgAD and hundreds for ADs, systematic cross-trait analyses are lacking, leaving the shared genetic architecture and underlying mechanisms poorly understood. In this study, we analyzed summary statistics from large-scale GWAS of IgAD and 10 common ADs. Cross-trait GWAS meta-analysis identified 51 pleiotropic loci significantly associated with IgAD and at least one AD (p < 5×10⁻⁸), 31 of which were novel for IgAD. Colocalization analysis further supported 33 shared loci between IgAD and ADs, including 19 novel IgAD loci, such as those near TNFAIP3, CD28, IRF4, STAT4, SH2B3, APOBR and RAD51B. Gene-level analysis revealed shared pathways involved in T-cell differentiation and the intestinal immune network for IgA production. Tissue heritability analysis identified whole blood and the intestine as critical tissues, while single-cell RNA sequencing (scRNA-seq) highlighted B cell subtypes in the peripheral blood and gut as the most affected cell types in IgAD and ADs. Mendelian randomization further demonstrated bidirectional causal relationships between IgAD and several ADs. Our findings reveal a shared genetic architecture between IgAD and ADs, highlighting common functional mechanisms and providing insights into their biological interplay and potential immune-based therapies.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ARHI as a key regulator of EMT and metastasis in pancreatic cancer via the Notch-1 pathway. ARHI通过Notch-1通路作为胰腺癌EMT和转移的关键调节因子。

IF 3.4 2区生物学

Human Genetics Pub Date : 2026-06-14 DOI: 10.1007/s00439-026-02845-2

Jingjing Liu, Yiqun Zhao, Ying Wang, Ying Shi, Qiang Zhi, Linlin Chen, Yuhao Ke, Jianlin Ren

引用次数: 0

Large-scale mitogenome analysis reveals complex maternal genetic connections between Sino-Tibetan- and Altaic-speaking populations. 大规模的有丝分裂基因组分析揭示了汉藏语系和阿尔泰语系人口之间复杂的母系遗传联系。

IF 3.4 2区生物学

Human Genetics Pub Date : 2026-06-13 DOI: 10.1007/s00439-026-02842-5

Yutong Jiang, Lintao Luo, Yunhui Liu, Lingqing Ou, Jiayan Liang, Limei Zhang, Moru Guo, Yanling Liu, Jie Zhong, Bowen Li, Zihao Zhu, Yuzhu Wang, Yuguo Huang, Chao Liu, Yuhang Feng, Guanglin He, Mengge Wang, Renkuan Tang

{"title":"Large-scale mitogenome analysis reveals complex maternal genetic connections between Sino-Tibetan- and Altaic-speaking populations.","authors":"Yutong Jiang, Lintao Luo, Yunhui Liu, Lingqing Ou, Jiayan Liang, Limei Zhang, Moru Guo, Yanling Liu, Jie Zhong, Bowen Li, Zihao Zhu, Yuzhu Wang, Yuguo Huang, Chao Liu, Yuhang Feng, Guanglin He, Mengge Wang, Renkuan Tang","doi":"10.1007/s00439-026-02842-5","DOIUrl":"10.1007/s00439-026-02842-5","url":null,"abstract":"The Sino-Tibetan and Altaic groups have played central roles in shaping the human demographic history of populations at the crossroads of East Asia and Siberia. However, their matrilineal relationships and links to complex cultural interactions remain poorly resolved. Here, we reported 344 newly sequenced complete mitogenomes from representative populations and integrated them with a curated dataset of more than 53,000 reference sequences. We uncovered a highly structured maternal genetic landscape, in which Sino-Tibetan and Altaic groups shared some maternal lineages despite distinct demographic trajectories, including East Asian haplogroups D4 and A. Sino-Tibetan-speaking populations showed elevated frequencies of B4, F1, and M7, whereas Altaic-speaking populations were enriched for C, H, and U. These observed genomic diversity patterns were jointly shaped by linguistic affiliation and geography. High-resolution phylogeographic analyses further showed that Tibeto-Burman groups from the Qinghai-Tibetan Plateau (QTP) carried distinctive maternal components, including region-specific sub-lineages within A, M9, and R32. Phylogenetic reconstructions dated the maternal lineages shared by Sino-Tibetan- and Altaic-speaking populations to 56.87-10.86 thousand years ago (kya), indicating that these early divergences formed the primary genetic foundation of both groups, whereas later Neolithic expansions contributed only modestly. Mongolic groups from the Inner Mongolian Plateau shared some maternal lineages with QTP populations, largely dating to 26.83-12.72 kya, indicating deep maternal connections despite substantial geographic separation.","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":"145 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0