European Journal of Human Genetics最新文献_第2页

Uncovering genetic diversity and admixture of British Africans with HLA alleles inferred from whole genome sequencing. 揭示英裔非洲人HLA等位基因的遗传多样性和混合。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-16 DOI: 10.1038/s41431-025-01888-9

Yunjia Liu, Ze Meng, Indra Adrianto, Albert M Levin, Qing-Sheng Mi, Qiang Wang, Hongsheng Gui

{"title":"Uncovering genetic diversity and admixture of British Africans with HLA alleles inferred from whole genome sequencing.","authors":"Yunjia Liu, Ze Meng, Indra Adrianto, Albert M Levin, Qing-Sheng Mi, Qiang Wang, Hongsheng Gui","doi":"10.1038/s41431-025-01888-9","DOIUrl":"https://doi.org/10.1038/s41431-025-01888-9","url":null,"abstract":"The human leukocyte antigen (HLA) region is highly diverse and plays a crucial role in immune regulation and antigen presentation. Accurate HLA typing is essential for understanding disease susceptibility, transplantation compatibility, and pharmacogenetics. However, its application in African descent populations is challenging due to complex linkage disequilibrium patterns and the lack of ancestry-matched populations in HLA reference panels. Here, we leveraged the latest whole-genome sequencing (WGS) data from UK Biobank African individuals to perform better HLA genotyping, and further utilized allelic and haplotypic data to explore population genetics patterns of this region. With WGS-inferred HLA alleles, we identified specific admixture patterns (predominant West and East African and minor European ancestries) within British African population, revealing their complex evolutionary history. Not only did we reveal the genetic diversity within this population, but also highlighted its differences from African Americans, ancestral Africans, and other global populations. We further identified regional ancestry differences in the HLA genomic region, highlighting discordance between global and local admixture estimates. British Africans also presented unique HLA frequency distributions for both typical and disease-associated alleles or haplotypes. These findings emphasize the need for expanding African-specific HLA reference panel and prove better HLA typing can be achieved by coupling sequencing technologies with computational approaches. The HLA genetic characteristics observed in British Africans provide valuable insights into population-specific immune responses and susceptibility. Overall, this study advances our understanding of HLA diversity and genetic admixture in British African population, with important implications for both disease mechanism and clinical utility.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648896","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

Implications of monogenic bicuspid aortic valve (BAV) forms among sporadic BAV patients. 散发性BAV患者单基因双尖瓣主动脉瓣（BAV）形态的意义。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-11 DOI: 10.1038/s41431-025-01909-7

Christopher M H Bruenger, Frank Oeffner, Laura L Koebbe, Sebastian Zimmer, Verena Veulemans, Matti Adam, Jessica Bigge, Stefanie Heilmann-Heimbach, Malte Kelm, Stephan Baldus, Markus M Nöthen, Georg Nickenig, Carlo Maj, Baravan Al-Kassou, Johannes Schumacher

{"title":"Implications of monogenic bicuspid aortic valve (BAV) forms among sporadic BAV patients.","authors":"Christopher M H Bruenger, Frank Oeffner, Laura L Koebbe, Sebastian Zimmer, Verena Veulemans, Matti Adam, Jessica Bigge, Stefanie Heilmann-Heimbach, Malte Kelm, Stephan Baldus, Markus M Nöthen, Georg Nickenig, Carlo Maj, Baravan Al-Kassou, Johannes Schumacher","doi":"10.1038/s41431-025-01909-7","DOIUrl":"https://doi.org/10.1038/s41431-025-01909-7","url":null,"abstract":"Bicuspid aortic valve (BAV) represents the most common congenital heart defect and is genetically heterogeneous. While the majority of cases results from common risk variants that confer disease cumulatively, a small proportion of BAV cases has a monogenic etiology where penetrant rare variants (RVs) in single genes are disease causing. We assessed the proportion of monogenic BAV cases in 740 non-syndromic and non-familial BAV patients that should be representative for cardiovascular centers of maximum care. We used next generation sequencing- (NGS-) based single-molecule molecular inversion probes (smMIPs) and analyzed all monogenic BAV genes that have been identified so far (NOTCH1, SMAD6, ROBO4, GATA4, GATA6, and ADAMTS19). In these genes, we identified potential damaging RVs in 2% of our patients, which were not significantly enriched compared to 726 population-based controls. We conclude that the contribution of monogenic BAV forms is only small among non-syndromic and sporadic BAV patients.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616904","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

Revising the reproductive story: psychosocial and reproductive impacts 12 months after reproductive genetic carrier screening. 修订生殖故事：生殖基因携带者筛查后12个月的心理社会和生殖影响。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-09 DOI: 10.1038/s41431-025-01903-z

Erin Tutty, Belinda J McClaren, Sharon Lewis, Kristine Barlow-Stewart, Tiffany Boughtwood, Jade Caruana, Jane L Halliday, Edwin P Kirk, Nigel G Laing, John Massie, Martin B Delatycki, Alison D Archibald

{"title":"Revising the reproductive story: psychosocial and reproductive impacts 12 months after reproductive genetic carrier screening.","authors":"Erin Tutty, Belinda J McClaren, Sharon Lewis, Kristine Barlow-Stewart, Tiffany Boughtwood, Jade Caruana, Jane L Halliday, Edwin P Kirk, Nigel G Laing, John Massie, Martin B Delatycki, Alison D Archibald","doi":"10.1038/s41431-025-01903-z","DOIUrl":"https://doi.org/10.1038/s41431-025-01903-z","url":null,"abstract":"The responsible implementation of reproductive genetic carrier screening (RGCS) involves understanding the long-term psychosocial and reproductive impacts of results. This mixed-methods study examined these impacts within 'Mackenzie's Mission', an Australia-wide study that offered couple-based RGCS for >1280 genes to 10,000 reproductive couples. Data from participant surveys completed at enrolment and 12 months post-result were analysed. Participants with an increased chance result were interviewed. Reflexive thematic analysis, guided by Interpretive Description was used. 4948 participants (27% response) completed the 12 month post-result survey. Most had minimal decision regret (median ≤5, 0 = no regret, 100 = high regret) and high reproductive confidence. Participants found to have an increased chance result had elevated anxiety (n = 116, median = 39 out of 80, clinically meaningful is ≥40). Interviewees (N = 19, from 16 couples) felt their increased chance result \"change[d] everything\" about their reproductive plans. Although revising their reproductive plan was an emotionally complex \"journey\", participants were \"grateful\" for the information. The concept of the 'Reproductive Story', was used to interpret the results. A reproductive story refers to a person's expected narrative about parenthood that, if altered, can cause psychosocial distress. Receiving an increased chance result disrupts the reproductive story. By 12 months post-result, most people with an increased chance result felt empowered to revise their reproductive story, but anxiety was elevated. Findings suggest a need for longitudinal models of post-RGCS psychosocial support.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599839","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

Vertical inheritance and unique differential phenotypes of reciprocal recombinant chromosome 18 within a multi-generation family. 多代家族中18号染色体的垂直遗传和独特的差异表型。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-08 DOI: 10.1038/s41431-025-01878-x

Ting Wen, Gulsen Akay, Janice Palumbos, Betsy Ostrander, Denise I Quigley, Allen N Lamb, Erica F Andersen, Bo Hong, David Viskochil

{"title":"Vertical inheritance and unique differential phenotypes of reciprocal recombinant chromosome 18 within a multi-generation family.","authors":"Ting Wen, Gulsen Akay, Janice Palumbos, Betsy Ostrander, Denise I Quigley, Allen N Lamb, Erica F Andersen, Bo Hong, David Viskochil","doi":"10.1038/s41431-025-01878-x","DOIUrl":"https://doi.org/10.1038/s41431-025-01878-x","url":null,"abstract":"Carriers of balanced pericentric inversions are at risk for producing unbalanced gametes because of meiotic recombination resulting in de novo deletion and duplication of distal chromosome ends. Recombinant chromosomes generally lead to significant imbalances resulting in anomalous clinical phenotypes in offspring, hence they are typically not inherited. Therefore, the vertical transmission of recombinant chromosomes is a clinically rare event. Using genomic microarray and karyotyping, we describe inheritance of recombinant chromosomes in a three-generation family with the grandmother carrying a mosaic pericentric inversion of chromosome 18. Three children inherited the balanced inversion and one child with a mild phenotype inherited a de novo recombinant chromosome 18. In the third generation, a newborn with a variant of holoprosencephaly inherited an unmodified recombinant chromosome from her mother. Despite having the same karyotype predicting loss of the TGIF1 gene from the 18p terminus, the mother exhibits a relatively unaffected phenotype. The cousin of the child with holoprosencephaly carries the reciprocal recombinant chromosome 18 with a much milder phenotype. We verified the cytogenetic mechanism and corresponding clinical phenotypes in affected individuals and illustrated possible recombinant chromosome consequences of the inversion of chromosome 18 in this three-generation family.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590795","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

Interrupted CTG repeats in the 37-43 units size range in the 3'UTR of DMPK are common alleles. DMPK 3'UTR中37-43个单位大小范围内的中断CTG重复序列是常见的等位基因。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-08 DOI: 10.1038/s41431-025-01907-9

Hilde Swinkels, Maike Leferink, Maartje Pennings, Bart van der Sanden, Christian Gilissen, Jordi Corominas Galbany, Erik-Jan Kamsteeg

{"title":"Interrupted CTG repeats in the 37-43 units size range in the 3'UTR of DMPK are common alleles.","authors":"Hilde Swinkels, Maike Leferink, Maartje Pennings, Bart van der Sanden, Christian Gilissen, Jordi Corominas Galbany, Erik-Jan Kamsteeg","doi":"10.1038/s41431-025-01907-9","DOIUrl":"10.1038/s41431-025-01907-9","url":null,"abstract":"The size of non-pathogenic CTG repeats in the 3'UTR of the DMPK gene varies from 5-35, whereas repeats over 50 units are pathogenic. The Intermediate repeats of 36-50 are considered 'premutation', as they are present in individuals unaffected by myotonic dystrophy, but are prone to further enlargement into the pathogenic range upon transmission to offspring. In this study, we showed that CCGCTG interrupted intermediate repeats, in the repeat size of 37-43 units, have been detected in multiple families with a history of myotonic dystrophy. However, segregation and microsatellite marker analysis of these interrupted intermediate alleles revealed that these alleles are not the same alleles (haplotypes) that were found expanded in affected family members. In contrast to the pure intermediate alleles, the CCGCTG intermediate repeats within families did not show intergenerational variability in size. Furthermore, we showed that the CCGCTG interrupted intermediate alleles have an allele frequency of approximately 0.35% in the general population, while CCGCTG interruptions were not detected in pathogenic repeat expansions over 50 repeat units in our control cohort. We postulate that intermediate repeats of size 37-43 having CCGCTG interruptions are not prone to further expansion, and therefore not act as premutations, which has great relevance for individuals with these alleles and has implications for genetic counseling and testing.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583464","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

Estimating the use of biological samples in Finnish biobanks and hospital collections. 估计芬兰生物库和医院收集的生物样本的使用情况。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-05 DOI: 10.1038/s41431-025-01906-w

Aaro Tupasela, Tom Southerington, Johanna Mäkelä, Lila Kallio, Merja Perälä, Veli-Matti Kosma, Arto Mannermaa, Tiina Jokela, Kimmo Pitkänen, Mika Kontro, Tiina Vesterinen, Eero Punkka, Theresa Knopp, Minna Ruddock, Raisa Serpi, Anne-Mari Moilanen, Leena Viiri, Sanna Siltanen, Enni Makkonen, Päivi Ingalsuo

{"title":"Estimating the use of biological samples in Finnish biobanks and hospital collections.","authors":"Aaro Tupasela, Tom Southerington, Johanna Mäkelä, Lila Kallio, Merja Perälä, Veli-Matti Kosma, Arto Mannermaa, Tiina Jokela, Kimmo Pitkänen, Mika Kontro, Tiina Vesterinen, Eero Punkka, Theresa Knopp, Minna Ruddock, Raisa Serpi, Anne-Mari Moilanen, Leena Viiri, Sanna Siltanen, Enni Makkonen, Päivi Ingalsuo","doi":"10.1038/s41431-025-01906-w","DOIUrl":"https://doi.org/10.1038/s41431-025-01906-w","url":null,"abstract":"Finland has steadily developed its biobanking infrastructures since the early 2010s. This article presents a systematic overview of the number of biological samples that have been provided for research since 2013 when the Finnish Biobank Act came into force. Using data from individual biobanks and from permits issued by Fimea (formerly Valvira), we present the most up-to-date and complete account of sample use at a national level. Between 2014 and 2023 a total of 1,474,881 samples were provided through 998 sample requests. A better understanding of the use of biological samples at the national level can help highlight the important impact biobanking has as an infrastructure for supporting research. We argue that developing standards can help in developing national biobanking strategies and identify areas where biobanking can be further developed. We also conclude that the ability to combine tissue samples and health data flexibly and efficiently is essential and needs to be secured also within the context of the European Health Data Space (EHDS).","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567302","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 homozygous frameshift variant in the CILK1 gene causes cranioectodermal dysplasia. CILK1基因的纯合子移码变异导致颅外胚层发育不良。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-04 DOI: 10.1038/s41431-025-01902-0

Abdullah Sezer, Sukru S Oner, Hanife Saat, Merve G Turan, Tulin Gungor, Sebiha Cevik, Asli Erol, Ferhan Yenisert, Kerem Catalbas, Derya Hazal Ozbakir, Sinem Kocagil, Oğuz Cilingir, Mehmet Ali Ergun, Oktay I Kaplan

{"title":"A homozygous frameshift variant in the CILK1 gene causes cranioectodermal dysplasia.","authors":"Abdullah Sezer, Sukru S Oner, Hanife Saat, Merve G Turan, Tulin Gungor, Sebiha Cevik, Asli Erol, Ferhan Yenisert, Kerem Catalbas, Derya Hazal Ozbakir, Sinem Kocagil, Oğuz Cilingir, Mehmet Ali Ergun, Oktay I Kaplan","doi":"10.1038/s41431-025-01902-0","DOIUrl":"https://doi.org/10.1038/s41431-025-01902-0","url":null,"abstract":"Cranioectodermal dysplasia (CED) is a ciliopathy characterized by skeletal and ectodermal abnormalities, renal failure, and liver fibrosis. Pathogenic variants in genes that encode the intraflagellar transport (IFT) complex components, particularly IFT-A, are responsible for approximately two-thirds of the CED cases. However, the cause of the remaining cases remains unknown. Ciliogenesis-associated kinase 1 (CILK1) is a highly conserved ciliary serine/threonine kinase with an N-terminal catalytic domain responsible for kinase activity and a C-terminal non-catalytic domain that interacts with the IFT-B complex. Biallelic variants in the catalytic domain are associated with lethal skeletal dysplasia, endocrine cerebroosteodysplasia, and short-rib polydactyly syndrome. No human disease has been linked to biallelic variants in the non-catalytic domain. We present a homozygous frameshift variant in the CILK1 gene that affects the distal part of the non-catalytic domain, causing CED in five patients from two pedigrees. All the patients survived into childhood and had disproportionately short stature, skeletal abnormalities, ectodermal dysplasia, renal issues, and liver complications. Functional data from patient-derived cells and the C. elegans model indicate that the variant reduces cilia number, increases cilia length, and disrupts the localization of IFT components. In contrast, the ciliary localization of CILK1 bearing the variant itself remains unaffected. Notably, we rescued the majority of these abnormalities by reintroducing CILK1 into patient-derived cells. Finally, our study describes CILK1 as a novel causal gene and the first non-IFT protein-encoding gene in the etiology of CED, thus expanding the known genotypic, mechanistic, and phenotypic spectrum of CED.","PeriodicalId":12016,"journal":{"name":"European Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564714","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

Summer reading 2025 in EJHG EJHG暑期阅读2025。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-03 DOI: 10.1038/s41431-025-01897-8

Alisdair McNeill

引用次数: 0

The role of untranslated region variants in Mendelian disease: a review. 非翻译区变异在孟德尔病中的作用：综述。

IF 4.6 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-03 DOI: 10.1038/s41431-025-01905-x

Nechama Wieder, Elston N D'Souza, Ruebena Dawes, Alexander Chan, Alexandra Martin-Geary, Nicola Whiffin

引用次数: 0

The European Certificate in Medical Genetics and Genomics (ECMGG). 欧洲医学遗传学和基因组学证书（ECMGG）。

IF 3.7 2区生物学

European Journal of Human Genetics Pub Date : 2025-07-02 DOI: 10.1038/s41431-025-01889-8

Peter D Turnpenny, Laura Pölsler, Ute Moog, Edward S Tobias, Angela Peron, Susanne E Boonen, Bonnie Lynch, Jonathan Berg

引用次数: 0