HGG Advances最新文献

{"title":"Biallelic NDC1 variants that interfere with ALADIN binding are associated with neuropathy and triple A-like syndrome.","authors":"Daphne J Smits, Jordy Dekker, Hannie Douben, Rachel Schot, Helen Magee, Somayeh Bakhtiari, Katrin Koehler, Angela Huebner, Markus Schuelke, Hossein Darvish, Shohreh Vosoogh, Abbas Tafakhori, Melika Jameie, Ehsan Taghiabadi, Yana Wilson, Margit Shah, Marjon A van Slegtenhorst, Evita G Medici-van den Herik, Tjakko J van Ham, Michael C Kruer, Grazia M S Mancini","doi":"10.1016/j.xhgg.2024.100327","DOIUrl":"10.1016/j.xhgg.2024.100327","url":null,"abstract":"<p><p>Nuclear pore complexes (NPCs) regulate nucleocytoplasmic transport and are anchored in the nuclear envelope by the transmembrane nucleoporin NDC1. NDC1 is essential for post-mitotic NPC assembly and the recruitment of ALADIN to the nuclear envelope. While no human disorder has been associated to one of the three transmembrane nucleoporins, biallelic variants in AAAS, encoding ALADIN, cause triple A syndrome (Allgrove syndrome). Triple A syndrome, characterized by alacrima, achalasia, and adrenal insufficiency, often includes progressive demyelinating polyneuropathy and other neurological complaints. In this report, diagnostic exome and/or RNA sequencing was performed in seven individuals from four unrelated consanguineous families with AAAS-negative triple A syndrome. Molecular and clinical studies followed to elucidate the pathogenic mechanism. The affected individuals presented with intellectual disability, motor impairment, severe demyelinating with secondary axonal polyneuropathy, alacrima, and achalasia. None of the affected individuals has adrenal insufficiency. All individuals presented with biallelic NDC1 in-frame deletions or missense variants that affect amino acids and protein domains required for ALADIN binding. No other significant variants associated with the phenotypic features were reported. Skin fibroblasts derived from affected individuals show decreased recruitment of ALADIN to the NE and decreased post-mitotic NPC insertion, confirming pathogenicity of the variants. Taken together, our results implicate biallelic NDC1 variants in the pathogenesis of polyneuropathy and a triple A-like disorder without adrenal insufficiency, by interfering with physiological NDC1 functions, including the recruitment of ALADIN to the NPC.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative trait locus mapping in placenta: A comparative study of chorionic villus and birth placenta.","authors":"Linda Dieckmann, Marius Lahti-Pulkkinen, Cristiana Cruceanu, Katri Räikkönen, Elisabeth B Binder, Darina Czamara","doi":"10.1016/j.xhgg.2024.100326","DOIUrl":"10.1016/j.xhgg.2024.100326","url":null,"abstract":"<p><p>The placenta, a pivotal player in the prenatal environment, holds crucial insights into early developmental pathways and future health outcomes. In this study, we explored genetic molecular regulation in chorionic villus samples (CVS) from the first trimester and placenta tissue at birth. We assessed quantitative trait locus (QTL) mapping on DNA methylation and gene expression data in a Finnish cohort of 574 individuals. We found more QTLs in birth placenta than in first-trimester placenta. Nevertheless, a substantial amount of associations overlapped in their effects and showed consistent direction in both tissues, with increasing molecular genetic effects from early pregnancy to birth placenta. The identified QTLs in birth placenta were most enriched in genes with placenta-specific expression. Conducting a phenome-wide-association study (PheWAS) on the associated SNPs, we observed numerous overlaps with genome-wide association study (GWAS) hits (spanning 57 distinct traits and 23 SNPs), with notable enrichments for immunological, skeletal, and respiratory traits. The QTL-SNP rs1737028 (chr6:29737993) presented with the highest number of GWAS hits. This SNP was related to HLA-G expression via DNA methylation and was associated with various immune, respiratory, and psychiatric traits. Our findings implicate increasing genetic molecular regulation during the course of pregnancy and support the involvement of placenta gene regulation, particularly in immunological traits. This study presents a framework for understanding placenta-specific gene regulation during pregnancy and its connection to health-related traits.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INDELpred: Improving the prediction and interpretation of indel pathogenicity within the clinical genome.","authors":"Yilin Wei, Tongda Zhang, Bangyao Wang, Xiaosen Jiang, Fei Ling, Mingyan Fang, Xin Jin, Yong Bai","doi":"10.1016/j.xhgg.2024.100325","DOIUrl":"10.1016/j.xhgg.2024.100325","url":null,"abstract":"<p><p>Small insertions and deletions (indels) are critical yet challenging genetic variations with significant clinical implications. However, the identification of pathogenic indels from neutral variants in clinical contexts remains an understudied problem. Here, we developed INDELpred, a machine-learning-based predictive model for discerning pathogenic from benign indels. INDELpred was established based on key features, including allele frequency, indel length, function-based features, and gene-based features. A set of comprehensive evaluation analyses demonstrated that INDELpred exhibited superior performance over competing methods in terms of computational efficiency and prediction accuracy. Importantly, INDELpred highlighted the crucial role of function-based features in identifying pathogenic indels, with a clear interpretability of the features in understanding the disease-causing variants. We envisage INDELpred as a desirable tool for the detection of pathogenic indels within large-scale genomic datasets, thereby enhancing the precision of genetic diagnoses in clinical settings.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stratified analyses refine association between TLR7 rare variants and severe COVID-19.","authors":"Jannik Boos, Caspar I van der Made, Gayatri Ramakrishnan, Eamon Coughlan, Rosanna Asselta, Britt-Sabina Löscher, Luca V C Valenti, Rafael de Cid, Luis Bujanda, Antonio Julià, Erola Pairo-Castineira, J Kenneth Baillie, Sandra May, Berina Zametica, Julia Heggemann, Agustín Albillos, Jesus M Banales, Jordi Barretina, Natalia Blay, Paolo Bonfanti, Maria Buti, Javier Fernandez, Sara Marsal, Daniele Prati, Luisa Ronzoni, Nicoletta Sacchi, Joachim L Schultze, Olaf Riess, Andre Franke, Konrad Rawlik, David Ellinghaus, Alexander Hoischen, Axel Schmidt, Kerstin U Ludwig","doi":"10.1016/j.xhgg.2024.100323","DOIUrl":"10.1016/j.xhgg.2024.100323","url":null,"abstract":"<p><p>Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10^-10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (OR_max = 46.5, p = 1.74 × 10^-15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Massively parallel reporter assay confirms regulatory potential of hQTLs and reveals important variants in lupus and other autoimmune diseases.","authors":"Yao Fu, Jennifer A Kelly, Jaanam Gopalakrishnan, Richard C Pelikan, Kandice L Tessneer, Satish Pasula, Kiely Grundahl, David A Murphy, Patrick M Gaffney","doi":"10.1016/j.xhgg.2024.100279","DOIUrl":"10.1016/j.xhgg.2024.100279","url":null,"abstract":"<p><p>We designed a massively parallel reporter assay (MPRA) in an Epstein-Barr virus transformed B cell line to directly characterize the potential for histone post-translational modifications, i.e., histone quantitative trait loci (hQTLs), expression QTLs (eQTLs), and variants on systemic lupus erythematosus (SLE) and autoimmune (AI) disease risk haplotypes to modulate regulatory activity in an allele-dependent manner. Our study demonstrates that hQTLs, as a group, are more likely to modulate regulatory activity in an MPRA compared with other variant classes tested, including a set of eQTLs previously shown to interact with hQTLs and tested AI risk variants. In addition, we nominate 17 variants (including 11 previously unreported) as putative causal variants for SLE and another 14 for various other AI diseases, prioritizing these variants for future functional studies in primary and immortalized B cells. Thus, we uncover important insights into the mechanistic relationships among genotype, epigenetics, and gene expression in SLE and AI disease phenotypes.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139933217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver regulatory mechanisms of noncoding variants at lipid and metabolic trait loci.","authors":"Gautam K Pandey, Swarooparani Vadlamudi, Kevin W Currin, Anne H Moxley, Jayna C Nicholas, Jessica C McAfee, K Alaine Broadaway, Karen L Mohlke","doi":"10.1016/j.xhgg.2024.100275","DOIUrl":"10.1016/j.xhgg.2024.100275","url":null,"abstract":"<p><p>Genome-wide association studies (GWASs) have identified hundreds of risk loci for liver disease and lipid-related metabolic traits, although identifying their target genes and molecular mechanisms remains challenging. We predicted target genes at GWAS signals by integrating them with molecular quantitative trait loci for liver gene expression (eQTL) and liver chromatin accessibility QTL (caQTL). We predicted specific regulatory caQTL variants at four GWAS signals located near EFHD1, LITAF, ZNF329, and GPR180. Using transcriptional reporter assays, we determined that caQTL variants rs13395911, rs11644920, rs34003091, and rs9556404 exhibit allelic differences in regulatory activity. We also performed a protein binding assay for rs13395911 and found that FOXA2 differentially interacts with the alleles of rs13395911. For variants rs13395911 and rs11644920 in putative enhancer regulatory elements, we used CRISPRi to demonstrate that repression of the enhancers altered the expression of the predicted target and/or nearby genes. Repression of the element at rs13395911 reduced the expression of EFHD1, and repression of the element at rs11644920 reduced the expression of LITAF, SNN, and TXNDC11. Finally, we showed that EFHD1 is a metabolically active gene in HepG2 cells. Together, these results provide key steps to connect genetic variants with cellular mechanisms and help elucidate the causes of liver disease.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, immunohistochemical, and genetic characterization of splice-altering biallelic DES variants: Therapeutic implications.","authors":"Janelle Geist Hauserman, Chamindra G Laverty, Sandra Donkervoort, Ying Hu, Sarah Silverstein, Sarah B Neuhaus, Dimah Saade, Gabrielle Vaughn, Denise Malicki, Rupleen Kaur, Yuesheng Li, Yan Luo, Poching Liu, Patrick Burr, A Reghan Foley, Payam Mohassel, Carsten G Bönnemann","doi":"10.1016/j.xhgg.2024.100274","DOIUrl":"10.1016/j.xhgg.2024.100274","url":null,"abstract":"<p><p>Pathogenic variants in the DES gene clinically manifest as progressive skeletal muscle weakness, cardiomyopathy with associated severe arrhythmias, and respiratory insufficiency, and are collectively known as desminopathies. While most DES pathogenic variants act via a dominant mechanism, recessively acting variants have also been reported. Currently, there are no effective therapeutic interventions for desminopathies of any type. Here, we report an affected individual with rapidly progressive dilated cardiomyopathy, requiring heart transplantation at age 13 years, in the setting of childhood-onset skeletal muscle weakness. We identified biallelic DES variants (c.640-13 T>A and c.1288+1 G>A) and show aberrant DES gene splicing in the affected individual's muscle. Through the generation of an inducible lentiviral system, we transdifferentiated fibroblast cultures derived from the affected individual into myoblasts and validated this system using RNA sequencing. We tested rationally designed, custom antisense oligonucleotides to screen for splice correction in these transdifferentiated cells and a functional minigene splicing assay. However, rather than correctly redirecting splicing, we found them to induce undesired exon skipping. Our results indicate that, while an individual precision-based molecular therapeutic approach to splice-altering pathogenic variants is promising, careful preclinical testing is imperative for each novel variant to test the feasibility of this type of approach for translation.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guidance on use of race, ethnicity, and geographic origin as proxies for genetic ancestry groups in biomedical publications.","authors":"W Gregory Feero, Robert D Steiner, Anne Slavotinek, Tiago Faial, Michael J Bamshad, Jehannine Austin, Bruce R Korf, Annette Flanagin, Kirsten Bibbins-Domingo","doi":"10.1016/j.xhgg.2024.100282","DOIUrl":"10.1016/j.xhgg.2024.100282","url":null,"abstract":"","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features.","authors":"Morad Ansari, Kamli N W Faour, Akiko Shimamura, Graeme Grimes, Emeline M Kao, Erica R Denhoff, Ana Blatnik, Daniel Ben-Isvy, Lily Wang, Benjamin M Helm, Helen Firth, Amy M Breman, Emilia K Bijlsma, Aiko Iwata-Otsubo, Thomy J L de Ravel, Vincent Fusaro, Alan Fryer, Keith Nykamp, Lara G Stühn, Tobias B Haack, G Christoph Korenke, Panayiotis Constantinou, Kinga M Bujakowska, Karen J Low, Emily Place, Jennifer Humberson, Melanie P Napier, Jessica Hoffman, Jane Juusola, Matthew A Deardorff, Wanqing Shao, Shira Rockowitz, Ian Krantz, Maninder Kaur, Sarah Raible, Victoria Dortenzio, Sabine Kliesch, Moriel Singer-Berk, Emily Groopman, Stephanie DiTroia, Sonia Ballal, Siddharth Srivastava, Kathrin Rothfelder, Saskia Biskup, Jessica Rzasa, Jennifer Kerkhof, Haley McConkey, Bekim Sadikovic, Sarah Hilton, Siddharth Banka, Frank Tüttelmann, Donald F Conrad, Anne O'Donnell-Luria, Michael E Talkowski, David R FitzPatrick, Philip M Boone","doi":"10.1016/j.xhgg.2024.100273","DOIUrl":"10.1016/j.xhgg.2024.100273","url":null,"abstract":"<p><p>Heterozygous missense variants and in-frame indels in SMC3 are a cause of Cornelia de Lange syndrome (CdLS), marked by intellectual disability, growth deficiency, and dysmorphism, via an apparent dominant-negative mechanism. However, the spectrum of manifestations associated with SMC3 loss-of-function variants has not been reported, leading to hypotheses of alternative phenotypes or even developmental lethality. We used matchmaking servers, patient registries, and other resources to identify individuals with heterozygous, predicted loss-of-function (pLoF) variants in SMC3, and analyzed population databases to characterize mutational intolerance in this gene. Here, we show that SMC3 behaves as an archetypal haploinsufficient gene: it is highly constrained against pLoF variants, strongly depleted for missense variants, and pLoF variants are associated with a range of developmental phenotypes. Among 14 individuals with SMC3 pLoF variants, phenotypes were variable but coalesced on low growth parameters, developmental delay/intellectual disability, and dysmorphism, reminiscent of atypical CdLS. Comparisons to individuals with SMC3 missense/in-frame indel variants demonstrated an overall milder presentation in pLoF carriers. Furthermore, several individuals harboring pLoF variants in SMC3 were nonpenetrant for growth, developmental, and/or dysmorphic features, and some had alternative symptomatologies with rational biological links to SMC3. Analyses of tumor and model system transcriptomic data and epigenetic data in a subset of cases suggest that SMC3 pLoF variants reduce SMC3 expression but do not strongly support clustering with functional genomic signatures of typical CdLS. Our finding of substantial population-scale LoF intolerance in concert with variable growth and developmental features in subjects with SMC3 pLoF variants expands the scope of cohesinopathies, informs on their allelic architecture, and suggests the existence of additional clearly LoF-constrained genes whose disease links will be confirmed only by multilayered genomic data paired with careful phenotyping.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olfactory receptor genes and chromosome 11 structural aberrations: Players or spectators?","authors":"Serena Redaelli, Francesca Romana Grati, Viviana Tritto, Giuliana Giannuzzi, Maria Paola Recalcati, Elena Sala, Nicoletta Villa, Francesca Crosti, Gaia Roversi, Francesca Malvestiti, Valentina Zanatta, Elena Repetti, Ornella Rodeschini, Chiara Valtorta, Ilaria Catusi, Lorenza Romitti, Emanuela Martinoli, Donatella Conconi, Leda Dalprà, Marialuisa Lavitrano, Paola Riva, Angela Bentivegna","doi":"10.1016/j.xhgg.2023.100261","DOIUrl":"10.1016/j.xhgg.2023.100261","url":null,"abstract":"<p><p>The largest multi-gene family in metazoans is the family of olfactory receptor (OR) genes. Human ORs are organized in clusters over most chromosomes and seem to include >0.1% the human genome. Because 369 out of 856 OR genes are mapped on chromosome 11 (HSA11), we sought to determine whether they mediate structural rearrangements involving this chromosome. To this aim, we analyzed 220 specimens collected during diagnostic procedures involving structural rearrangements of chromosome 11. A total of 222 chromosomal abnormalities were included, consisting of inversions, deletions, translocations, duplications, and one insertion, detected by conventional chromosome analysis and/or fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (array-CGH). We verified by bioinformatics and statistical approaches the occurrence of breakpoints in cytobands with or without OR genes. We found that OR genes are not involved in chromosome 11 reciprocal translocations, suggesting that different DNA motifs and mechanisms based on homology or non-homology recombination can cause chromosome 11 structural alterations. We also considered the proximity between the chromosomal territories of chromosome 11 and its partner chromosomes involved in the translocations by using the deposited Hi-C data concerning the possible occurrence of chromosome interactions. Interestingly, most of the breakpoints are located in regions highly involved in chromosome interactions. Further studies should be carried out to confirm the potential role of chromosome territories' proximity in promoting genome structural variation, so fundamental in our understanding of the molecular basis of medical genetics and evolutionary genetics.</p>","PeriodicalId":34530,"journal":{"name":"HGG Advances","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10820794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}