https://www.frontiersin.org/journals/genetics/sections/statistical-genetics-and-methodology RSS Feed for Statistical Genetics and Methodology section in the Frontiers in Genetics journal | New and Recent Articles en-us Frontiers Feed Generator,version:1 2026-05-13T21:27:08.544+00:00 60 https://www.frontiersin.org/articles/10.3389/fgene.2026.1807175 https://www.frontiersin.org/articles/10.3389/fgene.2026.1807175 2026-05-13T00:00:00Z Original Research Xiyao MaXiumei Zheng https://www.frontiersin.org/articles/10.3389/fgene.2026.1826365 https://www.frontiersin.org/articles/10.3389/fgene.2026.1826365 2026-03-26T00:00:00Z Correction Yanhuo ZhangChenghao QiuXingyu LiYaling PengJun LiuPeng Zhu https://www.frontiersin.org/articles/10.3389/fgene.2026.1733593 https://www.frontiersin.org/articles/10.3389/fgene.2026.1733593 2026-03-11T00:00:00Z Original Research Francesco BrunoPatrizia SpadaforaPaolo AbondioAntonio QualtieriErsilia PaparazzoMirella Aurora AcetoIda VeltriSelene De BenedittisBeatrice Maria GrecoAnnamaria CerantonioLuigi CitrignoGemma Di PalmaOlivier GalloGiuseppe PassarinoAlberto MontesantoFrancesca Cavalcanti https://www.frontiersin.org/articles/10.3389/fgene.2026.1758565 https://www.frontiersin.org/articles/10.3389/fgene.2026.1758565 2026-03-09T00:00:00Z Original Research Jingxuan LiWei LuoHonghao YuXishi HuangJisi MaShijun LiYong LiLantao Gu https://www.frontiersin.org/articles/10.3389/fgene.2026.1754817 https://www.frontiersin.org/articles/10.3389/fgene.2026.1754817 2026-03-02T00:00:00Z Original Research Yanhuo ZhangChenghao QiuXingyu LiYaling PengJun LiuPeng Zhu https://www.frontiersin.org/articles/10.3389/fgene.2026.1785502 https://www.frontiersin.org/articles/10.3389/fgene.2026.1785502 2026-02-18T00:00:00Z Original Research Zibin LinJiale XiangXiangzhong SunXinyu ShiXiaozhou LiuQinming CaiJing YangNana SongHaodong YeJiangfan XuJiguang PengXianghong OuYu SunZhiyu Peng G. For the novel missense variant LARS2 c.1661T>C, 3-D structural modeling and evolutionary conservation analysis were performed to evaluate its pathogenicity. Moreover, we comprehensively summarized all LARS2 variants associated with PS via an extensive literature review.ResultsProband 1 (12-year-old female) harbors compound heterozygous variants LARS2 c.235-2A>G (novel) and LARS2 c.880G>A, presenting with profound SNHL, primary ovarian insufficiency, and developmental delay. Proband 2 (7-year-old male) carries compound heterozygous variants LARS2 c.1661T>C (novel) and LARS2 c.1886C>T, manifesting severe SNHL with an unusual upsloping audiogram pattern and comprehension difficulties. Functional assays confirmed that LARS2 c.235-2A>G disrupts canonical splicing, leading to exon 4 skipping and in-frame deletions. 3-D structural modeling and conservation analysis revealed that LARS2 c.1661T>C likely impairs protein stability by altering residue interactions, with Val554 being highly conserved across species. According to the ACMG/AMP guideline, both novel LARS2 variants were classified as likely pathogenic.ConclusionWe identified two novel LARS2 variants associated with PS in Chinese patients, thereby expanding the LARS2 genetic spectrum and providing precise molecular evidence for clinical management and genetic counseling. This study enhances understanding of genotype-phenotype correlations in PS, thereby revealing the phenotypic heterogeneity of LARS2 variants.]]> https://www.frontiersin.org/articles/10.3389/fgene.2025.1708315 https://www.frontiersin.org/articles/10.3389/fgene.2025.1708315 2025-12-12T00:00:00Z Technology and Code Emil M. PedersenJette SteinbachCarsten B. PedersenAndrew J. SchorkMorten D. KrebsBjarni J. VilhjálmssonFlorian Privé https://www.frontiersin.org/articles/10.3389/fgene.2025.1710252 https://www.frontiersin.org/articles/10.3389/fgene.2025.1710252 2025-11-26T00:00:00Z Original Research Kai DengJingjing LiXitao HuHuijuan WeiChenyi WangQingqing ChengYu JiangLiyi CaiDi TangGuiju CaoXiaoyan Wang C and c.1552T>C) on pre-mRNA splicing, protein structure, and stability was assessed using bioinformatics tools. Functional validation was performed through in vitro rescue experiments in renal podocytes, quantifying effects on cellular morphology, ciliogenesis, and ciliary length. For preimplantation genetic testing (PGT), SNP haplotype analysis was employed for embryo selection.ResultsThe proband presented with renal failure and compound heterozygous TTC21B mutations (paternal c.895T>C [p.C299R] and maternal c.1552T>C [p.C518R]). Bioinformatics suggested potential splicing impacts, but minigene assays did not validate this. While c.895T>C had a minor impact on protein structure, c.1552T>C significantly altered the tertiary structure and stability. TTC21B knockdown disrupted podocyte morphology, which was fully rescued by wild-type TTC21B but only partially by either mutant. Both mutations impaired ciliogenesis and shortened ciliary length. PGT-M identified a mutation-free embryo (Embryo 1) for transfer, resulting in a healthy live birth.ConclusionThe compound heterozygous mutations c.895T>C (p.C299R) and c.1552T>C (p.C518R) in TTC21B contribute to NPHP12 by disrupting ciliogenesis and podocyte morphology. These findings provide targets for PGT-based embryo selection, successfully preventing the familial recurrence of this disease.]]> https://www.frontiersin.org/articles/10.3389/fgene.2025.1692704 https://www.frontiersin.org/articles/10.3389/fgene.2025.1692704 2025-10-27T00:00:00Z Original Research Nannan ZhangMiao HanTong ZhaoXinxin TangZhiwei WangYunqiu DuLeilei Wang https://www.frontiersin.org/articles/10.3389/fgene.2025.1686184 https://www.frontiersin.org/articles/10.3389/fgene.2025.1686184 2025-10-16T00:00:00Z Original Research Xunzhao ZhouQi YangQiuli ChenSheng YiShengkai WeiJingsi LuoDahua MengZailong QinShujie Zhang https://www.frontiersin.org/articles/10.3389/fgene.2025.1617504 https://www.frontiersin.org/articles/10.3389/fgene.2025.1617504 2025-09-01T00:00:00Z Original Research Wan-Yu Lin https://www.frontiersin.org/articles/10.3389/fgene.2025.1663455 https://www.frontiersin.org/articles/10.3389/fgene.2025.1663455 2025-08-26T00:00:00Z Original Research Huining JingBocheng XuHao WangShanling LiuHe WangJingqun MaiWencong YaoZhu Zhang T (p.R114L) and c.405-308_405-304del, were identified in both probands, each inherited from one unaffected parent. Both variants led to abnormal splicing. Specifically, the missense mutation c.341G>T caused the skipping of exon 4, whereas the novel deep-intronic variant c.405-308_405-304del created a new and strong acceptor site at c.405-294_405-293. Pathogenicity analysis indicated that both variants were pathogenic.ConclusionThis report presents a rare pedigree of recurrent MKS, in which two novel mutations in B9D1 are identified. Our findings expand the mutation spectrum of B9D1 and provide an accurate molecular diagnosis for genetic counseling.]]> https://www.frontiersin.org/articles/10.3389/fgene.2025.1654336 https://www.frontiersin.org/articles/10.3389/fgene.2025.1654336 2025-08-20T00:00:00Z Original Research Linbing ZouRuikang QiuZhijun DaiYulei LiYunjiao LiaoYan Zhou G (p.R224G) and c.1965+1dup, which was associated with the observed clinical phenotype. Bioinformatics analysis and in vivo/in vitro splicing assays demonstrated that the c.1965+1dup mutation disrupts MED25 pre-mRNA splicing, whereas the c.670C>G (p.R224G) variant does not exhibit this effect. However, bioinformatics analysis suggested that the mutation c.670C>G (p.R224G) may affect gene function by altering the structure of the MED25 protein.ConculsionThese findings demonstrated that two mutation sites identified in the MED25 gene in this case are pathogenic or likely pathogenic and may be associated with the clinical phenotype of the proband in this study.]]> https://www.frontiersin.org/articles/10.3389/fgene.2025.1416673 https://www.frontiersin.org/articles/10.3389/fgene.2025.1416673 2025-08-08T00:00:00Z Original Research David SoaveMelisa HayaliogluLei Sun https://www.frontiersin.org/articles/10.3389/fgene.2025.1660021 https://www.frontiersin.org/articles/10.3389/fgene.2025.1660021 2025-08-07T00:00:00Z Correction Yingtong WuYinggang CheYong ZhangYanlu XiongChen ShuJun JiangGaozhi LiLin GuoTianyun QiaoShuwen LiOu LiNing ChangXinxin ZhangMinzhe ZhangDan QiuHangtian XiJinggeng LiXiangxiang ChenMingxiang YeJian Zhang https://www.frontiersin.org/articles/10.3389/fgene.2025.1636065 https://www.frontiersin.org/articles/10.3389/fgene.2025.1636065 2025-08-04T00:00:00Z Original Research Jiaqi LiBingyu ZhangYe LiaoLiqin WeiQinfeng HuangLijun LinJiaxin ChenHui Chen https://www.frontiersin.org/articles/10.3389/fgene.2025.1649410 https://www.frontiersin.org/articles/10.3389/fgene.2025.1649410 2025-07-28T00:00:00Z Editorial Hongqiang LyuYao LiSijia WuLaiyi FuXiaoping LiangErhu Liu https://www.frontiersin.org/articles/10.3389/fgene.2025.1611138 https://www.frontiersin.org/articles/10.3389/fgene.2025.1611138 2025-07-09T00:00:00Z Brief Research Report Hongyan LiYue LinWeixu MaTing YuLingfeng DongYankun ChenShuming FanGuoqun LuoJingwen ZhangGe Song T) initially classified as a VUS. Sanger sequencing confirmed that the proband carried biallelic variants, whereas her sisters with either wild-type genotypes or a single heterozygous variant exhibited normal fertility, supporting the co-segregation of the identified variants. Critically, RNA assays demonstrated that the missense variant c.877G>T disrupts canonical splicing of PATL2, resulting in exon 12 skipping.ConclusionThis study provides the first experimental evidence that a PATL2 missense variant (c.877G>T) can exert its pathogenicity through aberrant splicing, supporting its pathogenic reclassification and elucidating a genotype-phenotype correlation for PATL2 missense variants through functional assays.]]> https://www.frontiersin.org/articles/10.3389/fgene.2025.1515260 https://www.frontiersin.org/articles/10.3389/fgene.2025.1515260 2025-07-04T00:00:00Z Brief Research Report Meiling ZhangXiao ChangXiaoyun DuZhen ChenXinyue ZhangFucheng Cai A (p.Pro255Glu) missense mutation in the HS6ST2 gene. Brain CT showed mild lateral ventricular enlargement, and electroencephalogram showed diffuse spikes and waves. Biochemical tests indicated significantly elevated transaminases, blood lactate values, and lactate/pyruvate values. Bioinformatics predictions suggest that this mutation may affect the thermal stability of the HS6ST2 protein. The amino acid where the mutation c.764C>A p.P255Q occurs is conserved across multiple species, specifically being proline in 13 species. In vitro cell experiments demonstrated that this mutant can impact the expression of HS6ST2 protein at post-transcriptional level. Comparison with previously reported cases revealed that different mutations might lead to different alternations in the function of HS6ST2 protein, resulting in distinct clinical phenotypes.]]> https://www.frontiersin.org/articles/10.3389/fgene.2025.1602234 https://www.frontiersin.org/articles/10.3389/fgene.2025.1602234 2025-07-01T00:00:00Z Mini Review Hongqiang LyuYao LiXinran ChenYuan LiuErhu LiuXiaoliang Cheng