Pub Date : 2026-01-01Epub Date: 2025-10-01DOI: 10.1016/j.gim.2025.101594
Alexander Bernier , Bartha Maria Knoppers , Jonathan Lawson , Robyn McDougall , Maili Raven-Adams , Vasiliki Rahimzadeh
Purpose
Standardizing contractual clauses that govern data access enables research institutions to responsibly steward genomic and related health data while enabling its efficient downstream reuse.
Methods
We describe a document analysis study using both qualitative and comparative law analytical approaches to identify the most common categories of clauses from 29 different data access agreements used by human biomedical research consortia globally. We furthermore characterized the legal positions and standard practices for each common element of the agreement and synthesized across them to develop model clauses. A total of 3 discussion sessions were organized virtually to refine the clauses among members of the Ethical Provenance Subgroup of the Global Alliance for Genomics and Health.
Results
We developed 15 unique data access clauses corresponding to the most common legal elements identified in the sampled agreements.
Conclusion
Model clauses can be used to drive administrative efficiencies and institutional compliance for managing access to human genomic data for research. Additional machine-readable consents and software solutions are needed to support traceable “ethical provenance” of human genomic data and communicate data use conditions throughout the data’s life-cycle.
{"title":"Toward ethical provenance tracking: The GA4GH model data access agreement (DAA)","authors":"Alexander Bernier , Bartha Maria Knoppers , Jonathan Lawson , Robyn McDougall , Maili Raven-Adams , Vasiliki Rahimzadeh","doi":"10.1016/j.gim.2025.101594","DOIUrl":"10.1016/j.gim.2025.101594","url":null,"abstract":"<div><h3>Purpose</h3><div>Standardizing contractual clauses that govern data access enables research institutions to responsibly steward genomic and related health data while enabling its efficient downstream reuse.</div></div><div><h3>Methods</h3><div>We describe a document analysis study using both qualitative and comparative law analytical approaches to identify the most common categories of clauses from 29 different data access agreements used by human biomedical research consortia globally. We furthermore characterized the legal positions and standard practices for each common element of the agreement and synthesized across them to develop model clauses. A total of 3 discussion sessions were organized virtually to refine the clauses among members of the Ethical Provenance Subgroup of the Global Alliance for Genomics and Health.</div></div><div><h3>Results</h3><div>We developed 15 unique data access clauses corresponding to the most common legal elements identified in the sampled agreements.</div></div><div><h3>Conclusion</h3><div>Model clauses can be used to drive administrative efficiencies and institutional compliance for managing access to human genomic data for research. Additional machine-readable consents and software solutions are needed to support traceable “ethical provenance” of human genomic data and communicate data use conditions throughout the data’s life-cycle.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 1","pages":"Article 101594"},"PeriodicalIF":6.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2026-01-06DOI: 10.1016/j.gim.2025.101600
Peter Burgard , Diana Ballhausen , Julia B. Hennermann , Georg F. Hoffmann , Stefan Kölker , Vassiliki Konstantopoulou , Robin Lachmann , Esther M. Maier , Elaine Murphy , Kurt Ullrich , Athanasia Ziagaki , Johannes Zschocke , Martin Lindner
{"title":"Correspondence on “Phenylalanine hydroxylase deficiency diagnosis and management: A 2023 evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)” by Smith et al","authors":"Peter Burgard , Diana Ballhausen , Julia B. Hennermann , Georg F. Hoffmann , Stefan Kölker , Vassiliki Konstantopoulou , Robin Lachmann , Esther M. Maier , Elaine Murphy , Kurt Ullrich , Athanasia Ziagaki , Johannes Zschocke , Martin Lindner","doi":"10.1016/j.gim.2025.101600","DOIUrl":"10.1016/j.gim.2025.101600","url":null,"abstract":"","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 1","pages":"Article 101600"},"PeriodicalIF":6.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-10-16DOI: 10.1016/j.gim.2025.101576
Andrew Giles , Kimberly Zayhowski , Maggie Ruderman , John Ranola , Grace E. VanNoy , Meghan Towne
Purpose
Race, ethnicity, and ancestry (REA) affect the diagnostic utility of genetic testing. In addition to barriers to accessing genetics services, some non-European REA groups experience decreased diagnostic results and increased uncertain results. Exome sequencing (ES) is a unique genetic test because data can be reanalyzed with new information and variants may be reclassified after the original result.
Methods
We performed a retrospective review of 10,416 clinical ES cases originally analyzed by Ambry Genetics between 2011 and 2021 with reanalysis events through 2023. The relationship between assigned REA group, ES result, reanalysis and reclassification rates, and reanalysis initiators were analyzed with logistic regression.
Results
Reanalyses increased the total diagnostic yield from 21.4% to 25.5%. There were no significant differences in reclassification rate among REA groups. However, the African American and Black group (P = 2.8E−07), the Hispanic and Latino group (P = .0022), and the Asian group (P = .033) were significantly less likely to receive provider-initiated reanalysis compared with the White group.
Conclusion
Although reclassification rates were not found to be associated with REA group, not all REA groups had the same access to ES reanalysis. Laboratory-initiated proactive reanalysis can help reduce disparities in ES diagnostic utility by reducing barriers to accessing reanalysis.
目的：人种、民族和血统（REA）影响基因检测的诊断效用。除了获得遗传学服务的障碍之外，一些非欧洲REA群体的诊断结果下降，不确定结果增加。外显子组测序（ES）是一种独特的基因检测方法，因为数据可以用新的信息重新分析，变异可以在原始结果之后重新分类。方法：我们对2011年至2021年间Ambry Genetics最初分析的10416例临床ES病例进行了回顾性分析，并进行了到2023年的再分析。采用logistic回归分析分配的REA组、ES结果、再分析和再分类率以及再分析启动因素之间的关系。结果：再分析将总诊断率从21.4%提高到25.5%。REA组间再分类率无显著性差异。然而，与白人组相比，非裔美国人和黑人组（P = 2.80 e -07），西班牙裔和拉丁裔组（P = 0.0022）和亚洲组（P = 0.033）接受提供者发起的再分析的可能性显着降低。结论：虽然再分类率与REA组没有相关性，但并非所有REA组都有相同的ES再分析机会。实验室发起的主动再分析可以通过减少获得再分析的障碍，帮助减少ES诊断效用的差异。
{"title":"Ten years of exome sequencing and reanalysis among racial, ethnic, and ancestral groups: The importance of equitable reanalysis access","authors":"Andrew Giles , Kimberly Zayhowski , Maggie Ruderman , John Ranola , Grace E. VanNoy , Meghan Towne","doi":"10.1016/j.gim.2025.101576","DOIUrl":"10.1016/j.gim.2025.101576","url":null,"abstract":"<div><h3>Purpose</h3><div>Race, ethnicity, and ancestry (REA) affect the diagnostic utility of genetic testing. In addition to barriers to accessing genetics services, some non-European REA groups experience decreased diagnostic results and increased uncertain results. Exome sequencing (ES) is a unique genetic test because data can be reanalyzed with new information and variants may be reclassified after the original result.</div></div><div><h3>Methods</h3><div>We performed a retrospective review of 10,416 clinical ES cases originally analyzed by Ambry Genetics between 2011 and 2021 with reanalysis events through 2023. The relationship between assigned REA group, ES result, reanalysis and reclassification rates, and reanalysis initiators were analyzed with logistic regression.</div></div><div><h3>Results</h3><div>Reanalyses increased the total diagnostic yield from 21.4% to 25.5%. There were no significant differences in reclassification rate among REA groups. However, the African American and Black group (<em>P</em> = 2.8E−07), the Hispanic and Latino group (<em>P</em> = .0022), and the Asian group (<em>P</em> = .033) were significantly less likely to receive provider-initiated reanalysis compared with the White group.</div></div><div><h3>Conclusion</h3><div>Although reclassification rates were not found to be associated with REA group, not all REA groups had the same access to ES reanalysis. Laboratory-initiated proactive reanalysis can help reduce disparities in ES diagnostic utility by reducing barriers to accessing reanalysis.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 1","pages":"Article 101576"},"PeriodicalIF":6.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-10-25DOI: 10.1016/j.gim.2025.101625
Tehmeena Akhter , Zubair M. Ahmed , Yaping Ji , Axel Schmidt , Meron Azage , Maria Palomares , Kirsten Cremer , Hartmut Engels , Jennifer O. Murphy , Sophia Peters , Elisabeth Mangold , M.L.Á. Gomez-Cano , Rodney J. Taylor , Sheikh Riazuddin , Saima Riazuddin
Purpose
Neurodevelopmental disorders (NDDs) are characterized by limitations in brain development. This study aims to determine the genetic causes of NDD in humans.
Methods
Exome sequencing was used to detect genetic variants of KLHL13, which encodes Kelch like protein 13 (KLHL13), in four families segregating in an X-linked pattern. In silico protein modeling and overexpression in heterologous cells were used to determine the variant’s impact. klhl13 loss of function was modeled in zebrafish, followed by rescue studies using human KLHL13 messenger RNA (mRNA) and an Aurora Kinase B (AURKB) inhibitor.
Results
We found one frameshift and three missense hemizygous variants of KLHL13 in individuals exhibiting NDD characteristics, such as intellectual disability (ID) and macrocephaly. Three-dimensional protein modeling simulation predicted the alteration of the KLHL13 protein folding for missense variants. Overexpression of NDD-associated variants in HEK293T cells revealed a significant impact on KLHL13-mediated cell-cycle regulation during mitosis, leading to genomic instability. Knocking down klhl13 in zebrafish resulted in developmental deficits, which were rescued by coinjection of human KLHL13WT messenger RNA but not by transcript encoding NDD variants. Treatment with AURKB selective inhibitor AZD1152-HQPA rescued genomic stability in heterologous cells and neurobehavioral deficits in zebrafish.
Conclusion
Our results implicate KLHL13-mediated AURKB regulation as a significant contributor to NDD in humans. Inhibiting AURKB activity could serve as a potential therapeutic approach to improve brain development and cognitive function.
{"title":"KLHL13 functional defects cause neurodevelopmental disorder in humans that can be rescued via inhibition of AURKB in cellular and animal models","authors":"Tehmeena Akhter , Zubair M. Ahmed , Yaping Ji , Axel Schmidt , Meron Azage , Maria Palomares , Kirsten Cremer , Hartmut Engels , Jennifer O. Murphy , Sophia Peters , Elisabeth Mangold , M.L.Á. Gomez-Cano , Rodney J. Taylor , Sheikh Riazuddin , Saima Riazuddin","doi":"10.1016/j.gim.2025.101625","DOIUrl":"10.1016/j.gim.2025.101625","url":null,"abstract":"<div><h3>Purpose</h3><div>Neurodevelopmental disorders (NDDs) are characterized by limitations in brain development. This study aims to determine the genetic causes of NDD in humans.</div></div><div><h3>Methods</h3><div>Exome sequencing was used to detect genetic variants of <em>KLHL13,</em> which encodes Kelch like protein 13 (KLHL13), in four families segregating in an X-linked pattern. <em>In silico</em> protein modeling and overexpression in heterologous cells were used to determine the variant’s impact. <em>klhl13</em> loss of function was modeled in zebrafish, followed by rescue studies using human <em>KLHL13</em> messenger RNA (mRNA) and an Aurora Kinase B (AURKB) inhibitor.</div></div><div><h3>Results</h3><div>We found one frameshift and three missense hemizygous variants of <em>KLHL13</em> in individuals exhibiting NDD characteristics, such as intellectual disability (ID) and macrocephaly. Three-dimensional protein modeling simulation predicted the alteration of the KLHL13 protein folding for missense variants. Overexpression of NDD-associated variants in HEK293T cells revealed a significant impact on KLHL13-mediated cell-cycle regulation during mitosis, leading to genomic instability. Knocking down <em>klhl13</em> in zebrafish resulted in developmental deficits, which were rescued by coinjection of human <em>KLHL13</em><sup>WT</sup> messenger RNA but not by transcript encoding NDD variants. Treatment with AURKB selective inhibitor AZD1152-HQPA rescued genomic stability in heterologous cells and neurobehavioral deficits in zebrafish.</div></div><div><h3>Conclusion</h3><div>Our results implicate KLHL13-mediated AURKB regulation as a significant contributor to NDD in humans. Inhibiting AURKB activity could serve as a potential therapeutic approach to improve brain development and cognitive function.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 1","pages":"Article 101625"},"PeriodicalIF":6.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-10-10DOI: 10.1016/j.gim.2025.101604
Ibrahim T. Khoja , Dawn S. Peck , Dimitar K. Gavrilov , Molly A. McPheron , Devin Oglesbee , Gisele Bentz Pino , Katie L. Sapp , Matthew J. Schultz , April L. Studinski Jones , Amy L. White , Silvia Tortorelli , Dietrich Matern , Patricia L. Hall
Purpose
To review the performance and outcomes of a second-tier newborn screening test for Pompe disease.
Methods
We followed our previously published screening approach that reduces false-positive results by incorporating creatine and creatinine levels and postanalytic tools in a second-tier test.
Results
We reviewed 1879 blood samples from neonates born in 11 states. Second-tier testing effectively reduced false-positive results, compared with first-tier enzyme testing alone. Only a small number of screen-positive cases (n = 7) were confirmed to have infantile-onset Pompe disease. No false-negative cases of infantile-onset Pompe disease were identified in this cohort, and 6 cases of possible late-onset Pompe disease were not detected with this approach.
Conclusion
This tiered screening strategy discriminated well between true- and false-positive results and improved the positive predictive value. However, it did not reliably differentiate between infantile- and late-onset Pompe disease.
{"title":"Reduction of false-positive results with biochemical second-tier testing for newborn screening of Pompe disease","authors":"Ibrahim T. Khoja , Dawn S. Peck , Dimitar K. Gavrilov , Molly A. McPheron , Devin Oglesbee , Gisele Bentz Pino , Katie L. Sapp , Matthew J. Schultz , April L. Studinski Jones , Amy L. White , Silvia Tortorelli , Dietrich Matern , Patricia L. Hall","doi":"10.1016/j.gim.2025.101604","DOIUrl":"10.1016/j.gim.2025.101604","url":null,"abstract":"<div><h3>Purpose</h3><div>To review the performance and outcomes of a second-tier newborn screening test for Pompe disease.</div></div><div><h3>Methods</h3><div>We followed our previously published screening approach that reduces false-positive results by incorporating creatine and creatinine levels and postanalytic tools in a second-tier test.</div></div><div><h3>Results</h3><div>We reviewed 1879 blood samples from neonates born in 11 states. Second-tier testing effectively reduced false-positive results, compared with first-tier enzyme testing alone. Only a small number of screen-positive cases (<em>n</em> = 7) were confirmed to have infantile-onset Pompe disease. No false-negative cases of infantile-onset Pompe disease were identified in this cohort, and 6 cases of possible late-onset Pompe disease were not detected with this approach.</div></div><div><h3>Conclusion</h3><div>This tiered screening strategy discriminated well between true- and false-positive results and improved the positive predictive value. However, it did not reliably differentiate between infantile- and late-onset Pompe disease.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 1","pages":"Article 101604"},"PeriodicalIF":6.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-02DOI: 10.1016/j.gim.2025.101619
Emma Wakeling , Rashida Baptiste , Clarissa Rocca , Bethan Hoskins , Christopher Clarkson , Lyn S. Chitty , Arianna Tucci
Purpose
Genome sequencing (GS) is increasingly used to investigate rare conditions, primarily in children. The 100,000 Genomes Project (100KG) evaluated GS ahead of implementation in the English National Health Service. In 2020, the National Health Service Genomic Medicine Service (GMS) became the first public health care system to offer GS in routine clinical care. We investigate how learning from 100KG informed GMS service delivery.
Methods
We compare GS outcomes in children tested at a large pediatric hospital via GMS (n = 501) and 100KG research (n = 1759).
Results
GMS diagnostic yield (29%) was higher than that in 100KG (22%) (P < .0016). Median age at testing was 8 years in 100KG and 6 in the GMS (P < .05). In 100KG, the diagnostic yield was <10% for 15 indications, none of which are included in GMS testing. 100KG data showed little benefit to application of >3 panels. Use of fewer but larger GMS panels resulted in a significantly higher number of genes tested per patient: median 2801 vs 1373 in 100KG (P < .001). In 100KG, diagnostic yield was not significantly increased by testing more than 3 family members (n = 34/142, 24%).
Conclusion
Learning from 100KG has informed GS clinical service delivery, resulting in higher diagnostic yields and earlier age at testing. Lessons are broadly applicable to all services providing GS, enabling earlier access to tailored management with fewer investigations.
{"title":"Delivering effective genome sequencing in pediatric care: From research in the 100,000 Genomes Project to routine clinical practice","authors":"Emma Wakeling , Rashida Baptiste , Clarissa Rocca , Bethan Hoskins , Christopher Clarkson , Lyn S. Chitty , Arianna Tucci","doi":"10.1016/j.gim.2025.101619","DOIUrl":"10.1016/j.gim.2025.101619","url":null,"abstract":"<div><h3>Purpose</h3><div>Genome sequencing (GS) is increasingly used to investigate rare conditions, primarily in children. The 100,000 Genomes Project (100KG) evaluated GS ahead of implementation in the English National Health Service. In 2020, the National Health Service Genomic Medicine Service (GMS) became the first public health care system to offer GS in routine clinical care. We investigate how learning from 100KG informed GMS service delivery.</div></div><div><h3>Methods</h3><div>We compare GS outcomes in children tested at a large pediatric hospital via GMS (<em>n</em> = 501) and 100KG research (<em>n</em> = 1759).</div></div><div><h3>Results</h3><div>GMS diagnostic yield (29%) was higher than that in 100KG (22%) (<em>P</em> < .0016). Median age at testing was 8 years in 100KG and 6 in the GMS (<em>P</em> < .05). In 100KG, the diagnostic yield was <10% for 15 indications, none of which are included in GMS testing. 100KG data showed little benefit to application of >3 panels. Use of fewer but larger GMS panels resulted in a significantly higher number of genes tested per patient: median 2801 vs 1373 in 100KG (<em>P</em> < .001). In 100KG, diagnostic yield was not significantly increased by testing more than 3 family members (<em>n</em> = 34/142, 24%).</div></div><div><h3>Conclusion</h3><div>Learning from 100KG has informed GS clinical service delivery, resulting in higher diagnostic yields and earlier age at testing. Lessons are broadly applicable to all services providing GS, enabling earlier access to tailored management with fewer investigations.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 1","pages":"Article 101619"},"PeriodicalIF":6.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2026-01-06DOI: 10.1016/j.gim.2025.101636
Daffodil M. Canson , George A.R. Wiggins , Logan C. Walker , Amanda B. Spurdle
{"title":"Correspondence on “Genome sequencing reveals the impact of pseudoexons in rare genetic disease” by Pitsava et al","authors":"Daffodil M. Canson , George A.R. Wiggins , Logan C. Walker , Amanda B. Spurdle","doi":"10.1016/j.gim.2025.101636","DOIUrl":"10.1016/j.gim.2025.101636","url":null,"abstract":"","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 1","pages":"Article 101636"},"PeriodicalIF":6.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-10-21DOI: 10.1016/j.gim.2025.101614
Steven Pastor , Oanh Tran , Ryan Lapointe , Arnold Z. Olali , Douglas C. Wallace , Bernice Morrow , Elaine H. Zackai , Donna M. McDonald-McGinn , Beverly S. Emanuel
Purpose
The genomic architecture of 22q11.2 deletion syndrome (22q11.2DS) has primarily been studied in White populations, despite evidence suggesting a lower prevalence in Black individuals. This study aims to improve our understanding of the population-specific organization of 22q11.2 genomic structures.
Methods
Optical mapping data from 106 genomes, representing various Black and White individuals, were analyzed to assess the structure and variation of the 22q11.2 low copy repeats (LCR22s).
Results
Extensive variability in copy-number and orientation of LCR22 elements was observed between Black and White genomes. Several novel copy-number variants and haplotype configurations were identified, some being private or more prevalent within specific groups. Notably, copy-number variants diversity was particularly striking among Black genomes. Comparisons of Black and White families with de novo 22q11.2DS probands revealed unique nonallelic homologous recombination scenarios, with Black families exhibiting recombination patterns that are not previously observed.
Conclusion
Perhaps the unique and highly variable LCR22 haplotype configurations in Black individuals contribute to the lower observed prevalence of 22q11.2DS by inhibiting the likelihood of nonallelic homologous recombination, the mechanism that leads to the syndrome.
{"title":"Optical mapping in Black genomes: Distinct LCR22 structures and 22q11.2 deletion syndrome mechanisms","authors":"Steven Pastor , Oanh Tran , Ryan Lapointe , Arnold Z. Olali , Douglas C. Wallace , Bernice Morrow , Elaine H. Zackai , Donna M. McDonald-McGinn , Beverly S. Emanuel","doi":"10.1016/j.gim.2025.101614","DOIUrl":"10.1016/j.gim.2025.101614","url":null,"abstract":"<div><h3>Purpose</h3><div>The genomic architecture of 22q11.2 deletion syndrome (22q11.2DS) has primarily been studied in White populations, despite evidence suggesting a lower prevalence in Black individuals. This study aims to improve our understanding of the population-specific organization of 22q11.2 genomic structures.</div></div><div><h3>Methods</h3><div>Optical mapping data from 106 genomes, representing various Black and White individuals, were analyzed to assess the structure and variation of the 22q11.2 low copy repeats (LCR22s).</div></div><div><h3>Results</h3><div>Extensive variability in copy-number and orientation of LCR22 elements was observed between Black and White genomes. Several novel copy-number variants and haplotype configurations were identified, some being private or more prevalent within specific groups. Notably, copy-number variants diversity was particularly striking among Black genomes. Comparisons of Black and White families with de novo 22q11.2DS probands revealed unique nonallelic homologous recombination scenarios, with Black families exhibiting recombination patterns that are not previously observed.</div></div><div><h3>Conclusion</h3><div>Perhaps the unique and highly variable LCR22 haplotype configurations in Black individuals contribute to the lower observed prevalence of 22q11.2DS by inhibiting the likelihood of nonallelic homologous recombination, the mechanism that leads to the syndrome.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 1","pages":"Article 101614"},"PeriodicalIF":6.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-04DOI: 10.1016/j.gim.2025.101631
Aantaki Raisa , Irania Santaliz Moreno , Amy Ayala , Jada G. Hamilton , Jessica Mozersky , Erin Linnenbringer , Julia Maki , Amy McQueen , George P. Souroullas , Erika A. Waters
Purpose
This study aimed to explore how health-related epigenetic concepts are depicted in YouTube videos, a widely accessed platform for informal science education. As epigenetics becomes increasingly relevant to medical therapeutics, it is essential to understand what information is being disseminated in the public sphere.
Methods
We conducted a content analysis of 296 YouTube videos about epigenetics that were under 10 minutes in length. We transcribed and analyzed the videos using an iteratively developed codebook and then categorized relevant codes as categories.
Results
We identified 7 categories: (1) defining epigenetics, (2) causes of epigenetic changes, (3) effects of epigenetic change, (4) epigenetic inheritability, (5) application of epigenetics, (6) personal control, and (7) epigenetic mysticism. Although the content about the molecular epigenetic mechanisms mostly aligned with the latest scientific findings, there were numerous unsubstantiated and exaggerated claims about effects of epigenetics on human health, especially disease outcomes.
Conclusion
We identified several scientific concepts described on YouTube regarding epigenetics. Our findings also reveal what information about epigenetics is widely shared in the public sphere, helping to identify key misconceptions to address and guiding the development of strategies for accurate scientific communication.
{"title":"A content analysis of health-related epigenetic information in YouTube videos","authors":"Aantaki Raisa , Irania Santaliz Moreno , Amy Ayala , Jada G. Hamilton , Jessica Mozersky , Erin Linnenbringer , Julia Maki , Amy McQueen , George P. Souroullas , Erika A. Waters","doi":"10.1016/j.gim.2025.101631","DOIUrl":"10.1016/j.gim.2025.101631","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to explore how health-related epigenetic concepts are depicted in YouTube videos, a widely accessed platform for informal science education. As epigenetics becomes increasingly relevant to medical therapeutics, it is essential to understand what information is being disseminated in the public sphere.</div></div><div><h3>Methods</h3><div>We conducted a content analysis of 296 YouTube videos about epigenetics that were under 10 minutes in length. We transcribed and analyzed the videos using an iteratively developed codebook and then categorized relevant codes as categories.</div></div><div><h3>Results</h3><div>We identified 7 categories: (1) defining epigenetics, (2) causes of epigenetic changes, (3) effects of epigenetic change, (4) epigenetic inheritability, (5) application of epigenetics, (6) personal control, and (7) epigenetic mysticism. Although the content about the molecular epigenetic mechanisms mostly aligned with the latest scientific findings, there were numerous unsubstantiated and exaggerated claims about effects of epigenetics on human health, especially disease outcomes.</div></div><div><h3>Conclusion</h3><div>We identified several scientific concepts described on YouTube regarding epigenetics. Our findings also reveal what information about epigenetics is widely shared in the public sphere, helping to identify key misconceptions to address and guiding the development of strategies for accurate scientific communication.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 1","pages":"Article 101631"},"PeriodicalIF":6.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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