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{"title":"Developing and applying a virus-induced gene silencing system for functional genomics in walnut (Juglans regia L.) mediated by tobacco rattle virus","authors":"Yaoxin Liu ,&nbsp;Yongjie Xu ,&nbsp;Haodong Xu ,&nbsp;Wulamurusuli Amilijiang ,&nbsp;Hua Wang","doi":"10.1016/j.gene.2024.149087","DOIUrl":"10.1016/j.gene.2024.149087","url":null,"abstract":"<div><div>Walnut (<em>Juglans regia</em> L.) is a high-value tree species planted worldwide, but the incomplete less developed genetic transformation system limits its gene function analysis. In this study, virus-induced gene silencing (VIGS) mediated by tobacco rattle virus (TRV) technology was applied to walnut seedlings to degrade the transcript of target gene. Different infiltration methods were used to explore the effects of infection mode, <em>Agrobacterium</em> cell density, silencing fragment length, and walnut cultivars. The results showed that spray infiltration of seedlings resulted in a photobleaching phenotype of the whole plant. Leaf injection was a more effective way of infiltration. The optimal combination was the <em>Agrobacterium</em> cell density at OD₆₀₀ = 1.1 with target fragment = 255 bp for the treatment of walnut early-fruiting cultivar ’Xiangling.’ This combination can reach up to 48 % of gene silencing efficiency. Based on this optimized VIGS system, silencing a walnut chlorophyll synthesis-related gene, <em>JrPOR</em> (Protochlorophyllide reductase), to further validate the system’s effect. The results showed that the expression of <em>JrPOR</em> was significantly repressed, and the chlorophyll level of the silenced plants was significantly decreased compared with the control. The above results indicate that the walnut TRV-VIGS system has been successfully established and can be used for reverse genetic studies, providing an option for verifying gene function in walnut.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149087"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the camelina MBOAT gene family: Phylogenetic insights and regulatory landscape","authors":"Pengfang Qiao,&nbsp;Maoqiu Zhao,&nbsp;Jialiang Zhao,&nbsp;Jiayin Wen,&nbsp;Cuizhu Zhao,&nbsp;Meng Zhang","doi":"10.1016/j.gene.2024.149085","DOIUrl":"10.1016/j.gene.2024.149085","url":null,"abstract":"<div><div>The membrane-bound O-acyltransferase (MBOAT) gene family comprises enzymes responsible for transferring acyl groups to various lipid molecules. Some members of the MBOAT gene family and their functions have been extensively studied in the model plant Arabidopsis. However, research on the MBOAT gene family in camelina is still limited. In this study, 54 MBOATs were identified on 17 chromosomes and one unidentified scaffold in camelina, including seven newly identified genes. A total of 149 MBOATs were identified in 10 other species. Six subgroups of these MBOATs with different conservation were classified by phylogenetic analysis, showing diversification between monocots and dicots. Detailed analysis of the motif composition, evolutionary relationships, and gene structures of CsaMBOATs are presented. The results of the syntenic analysis suggest that the evolution of CsaMBOAT gene family is primarily driven by segmental and tandem duplications, and that there is a stronger collinearity within dicots. In addition, analysis of CsaMBOAT gene promoter <em>cis</em>-elements reveals a possible transcriptional regulation and tissue-specific expression, highlighting potential role in plant stress responses and hormone signaling. Furthermore, both the transcriptome and RT-qPCR data revealed the changes in the expression levels of <em>DGAT1</em> during salt stress treatment. Subsequent analyses indicated that <em>DGAT1</em> influenced the ratio of fatty acid fractions in the plants. Importantly, a large number of transcription factors involved in the regulation of CsaMBOAT gene expression were identified by WGCNA analysis, and the transcriptional data confirmed that the <em>NAC032</em> and <em>CAMMTA6</em> genes play a role upstream of <em>DGAT1</em>. This study not only identified the members of the MBOAT in camelina, but also provided insights and clues into its regulatory mechanisms.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149085"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel frameshift mutation in the DIAPH1 gene causes a Chinese family autosomal dominant nonsyndromic hearing loss","authors":"Qi Feng ,&nbsp;Lu Jiang ,&nbsp;Shuai Zhang ,&nbsp;Chufeng He ,&nbsp;Lingyun Mei ,&nbsp;Yalan Liu","doi":"10.1016/j.gene.2024.149088","DOIUrl":"10.1016/j.gene.2024.149088","url":null,"abstract":"<div><h3>Objective</h3><div>This study reports a novel heterozygous, likely truncating mutation in the diaphanous homolog 1 (<em>DIAPH1</em>) gene associated with non-syndromic hearing loss.</div></div><div><h3>Methods</h3><div>Family members underwent audiological and imaging assessments, whole-exome sequencing (WES), and Sanger sequencing.</div></div><div><h3>Results</h3><div>Sensorineural hearing loss was observed in all five individuals, with severity ranging from mild to severe. None of the affected patients reported vestibular complaints, and routine blood tests showed normal platelet counts. Whole-exome sequencing (WES) revealed a novel frameshift variation, c.3555delA (p.Gln1185Hisfs*3), in exon 26 of the <em>DIAPH1</em> gene. This variation co-segregated with the hearing-impaired phenotype in the family. The data collected support the classification of c.3555delA as a genetic etiology of hereditary hearing loss according to the American College of Medical Genetics and Genomics guidelines.</div></div><div><h3>Conclusion</h3><div>We identified a novel pathogenic mutation in the <em>DIAPH1</em> gene, thereby expanding the mutation spectrum associated with hearing loss.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149088"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intergenerational effects of maternal rate of body weight gain on the multi-omics hepatic profiles of bovine fetuses","authors":"Muhammad Anas ,&nbsp;Alison K. Ward ,&nbsp;Kacie L. McCarthy ,&nbsp;Pawel P. Borowicz ,&nbsp;Lawrence P. Reynolds ,&nbsp;Joel S. Caton ,&nbsp;Carl R. Dahlen ,&nbsp;Wellison J.S. Diniz","doi":"10.1016/j.gene.2024.149082","DOIUrl":"10.1016/j.gene.2024.149082","url":null,"abstract":"<div><div>Maternal periconceptual nutrition affects the growth trajectory of developing fetuses by modulating gene expression. The regulatory mechanisms and their role in fetal development remain underexplored in livestock models. Herein, we investigated the effects of maternal rate of body weight (BW) gain during early gestation on the DNA methylation, microRNA profiles, and their interaction with the hepatic gene expression in female fetuses. At breeding, 36 crossbred beef heifers (∼13 months of age) were randomly assigned to a nutritional plane to gain Low (0.28 kg/day; <strong>LG</strong>, n = 18) or Moderate (0.79 kg/day; <strong>MG</strong>, n = 18) BW through the first 83 days of gestation. A subset of pregnant heifers (n = 17) was selected, and fetal liver samples were collected on day 83 of gestation for DNA methylation and miRNA-Sequencing. After data quality control, miRDeep2 and Bismark tools were used to analyze miRNA and methylation data, respectively. The bta-miR-206 was the only differentially expressed miRNA (FDR = 0.02). Eight differentially methylated genes were identified (DMGs, FDR &lt; 0.1). The over-represented pathways and biological processes (adj. <em>p</em> &lt; 0.05) for bta-miR-206 targeted genes were associated with embryonic development, energy metabolism, and mineral transport, whereas the DMGs regulated anatomical structural development and transcriptional regulation. Our results show that key genes involved with liver metabolism, tissue structure, and function were regulated by DNA methylation and the miR-206. However, further investigation is warranted to determine physiological responses and long-term consequences on animal performance.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149082"},"PeriodicalIF":2.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Masculinizing gene is a candidate male pathway developmental factor in the mud crab Scylla paramamosain","authors":"Chang Liu ,&nbsp;Bohao Peng ,&nbsp;Pengfei Zou ,&nbsp;Xiwei Jia ,&nbsp;Zhihua Zou ,&nbsp;Jiaxi Zhang ,&nbsp;Ziping Zhang ,&nbsp;Yilei Wang","doi":"10.1016/j.gene.2024.149083","DOIUrl":"10.1016/j.gene.2024.149083","url":null,"abstract":"<div><div>The <em>Masculinizer</em> (<em>Masc</em>) gene plays a crucial role in masculinization during insect embryonic gonadal development. Nevertheless, the <em>Masc</em> expression pattern and function in crabs remain largely unknown. In the present study, we screened and validated the <em>Masc</em> gene from transcriptome data of mud crab <em>S. paramamosain</em>. The <em>Masc</em> relative transcript level in the testis was significantly higher than that of ovaries and other tissues, as measured by quantitative real-time PCR. <em>In situ</em> hybridization showed that <em>Masc</em> exhibited a significant signal throughout all stages of testicular development. The phylogenetic analysis revealed conservation in the evolution of crustaceans, potentially indicating its functional importance. <em>Masc</em> RNA interference showed that the expression of testis bias-related genes decreased significantly while the ovary bias-related genes increased significantly. Transcriptome data suggested that <em>Masc</em> regulates several signaling pathways, including the mTOR, Wnt, insulin, and other sex-related pathways. These results indicate that <em>Masc</em> may play a role in mud crab male development with possible application in sex control in aquaculture.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"935 ","pages":"Article 149083"},"PeriodicalIF":2.6,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The plastomes of Cypripedium (Orchidaceae: Cypripedioideae) exhibit atypical GC content and genome size based on different sequencing strategies","authors":"Fu-Chao Guo ,&nbsp;Jia-Xing Yang ,&nbsp;Yan-Yan Guo","doi":"10.1016/j.gene.2024.149086","DOIUrl":"10.1016/j.gene.2024.149086","url":null,"abstract":"<div><div>Most of the sequenced plastomes of photosynthetic angiosperms exhibit conservation in size, gene content, gene order, and GC content. In contrast, the sequenced plastomes of <em>Cypripedium</em> are distinguished by genome size expansion, AT-biased base composition, structural variation, and a low substitution rate. Additionally, the impact of sequencing methods is seldom addressed in prior studies, and the species represented in these studies are underrepresented. These atypical plastome features render the genus an ideal candidate for investigating plastome evolution. Besides, the backbone relationships within the genus remain poorly resolved. In this study, we sequenced twelve <em>Cypripedium</em> plastomes using three distinct sequencing strategies and obtained an additional 27 sequences from GenBank for comparative analysis. We classified the plastomes of the genus into two types: one resembling those of most other angiosperms, and the other characterized by inverted repeat (IR) expansion and small single copy (SSC) contraction. The plastomes within this genus exhibit significant size variations (∼72 kb), variations in GC content, and structural differences at the genus level. Furthermore, our comparative analysis revealed that the choice of sequencing strategy significantly impacts the assembly results. The uncovered regions in samples sequenced with short-read technology are predominantly AT-rich, suggesting that short-read sequencing may lead to assembly errors in plastomes with AT-rich regions and long repeats. Additionally, we have reconstructed the phylogeny of the genus using plastome-level data. However, the phylogenetic relationships within the genus remain partially solved. This study provides new insights into the evolution of plastomes, particularly those with AT-rich base compositions and genomes containing long repeat regions.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"935 ","pages":"Article 149086"},"PeriodicalIF":2.6,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The goat PRLR gene: mRNA expression, association analysis of InDel variants with body weight and growth traits","authors":"Congliang Wang ,&nbsp;Zhaofei Ren ,&nbsp;Xiaoyu Liu ,&nbsp;Xiaoyue Song ,&nbsp;Lei Shi ,&nbsp;Huaiyan Kang ,&nbsp;Dong Ma ,&nbsp;Xianyong Lan ,&nbsp;Lei Qu ,&nbsp;Haijing Zhu ,&nbsp;Jinlian Hua","doi":"10.1016/j.gene.2024.149081","DOIUrl":"10.1016/j.gene.2024.149081","url":null,"abstract":"<div><div>Prolactin is a single-chain peptide hormone produced by the anterior pituitary gland and plays an important role in the reproductive development of mammals. Therefore, we investigated the expression of the <em>PRLR</em> gene in various goat tissues during distinct developmental stages, as well as the correlation between the 16 bp InDel and growth traits in goats. The study findings demonstrated a consistent expression and distribution of <em>PRLR</em> in both yearling and adult goat tissues, with the highest levels observed in the testis. Association analysis showed that in the yearling IMWC goat population (n = 463), this 16 bp InDel variation was associated with body weight (<em>P</em> = 0.026), body height (<em>P</em> = 0.005), body length (<em>P</em> = 0.008), heart girth (<em>P</em> = 0.001), chest depth (P = 0.000075), and chest width (<em>P</em> = 0.005); In the adult IMWC goat population (<em>n</em> = 211), the 16 bp InDel variation was associated with body height (<em>P</em> = 0.011), height across the hip (<em>P</em> = 0.0003), chest depth (<em>P</em> = 0.001), and cashmere fineness (<em>P</em> = 0.022); In all IMWC goat populations (<em>n</em> = 674), this 16 bp InDel was related to body weight (<em>P</em> = 0.042), body height (<em>P</em> = 0.001), body length (<em>P</em> = 0.013), heart girth (<em>P</em> = 0.012), height across the hip (<em>P</em> = 0.038), chest depth (<em>P</em> = 0.001), and chest width (<em>P</em> = 0.006). The bioinformatics analysis has revealed that the significant impact of a 16 bp InDel on growth traits in goats may be attributed to its specific binding to the transcription factors AP-2α and Sp1. These findings suggest that this genetic variant plays a crucial role in the growth and development of goats, making it a valuable DNA marker for selecting goats with superior growth traits.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"935 ","pages":"Article 149081"},"PeriodicalIF":2.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-disease drug discovery based on bioinformatics and virtual screening: Study of key genes in Alzheimer’s disease and ovarian cancer","authors":"Ziyi Shen ,&nbsp;Jinxuan Song ,&nbsp;Shenglin Wang ,&nbsp;Ming Tang ,&nbsp;Yang Yang ,&nbsp;Meiling Yu ,&nbsp;Rong Zhang ,&nbsp;Honggui Zhou ,&nbsp;Guohui Jiang","doi":"10.1016/j.gene.2024.149084","DOIUrl":"10.1016/j.gene.2024.149084","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) and cancer, both age-related diseases, are characterized by abnormal cellular behavior. Epidemiological data indicate an inverse relationship between AD and various cancers. Accordingly, this study seeks to analyze the negatively correlated genes between AD and ovarian cancer and identify closely related compounds through virtual screening technology to explore potential therapeutic drugs.</div></div><div><h3>Methods</h3><div>Microarray data were downloaded from the Gene Expression Omnibus database, and negatively correlated genes between AD and ovarian cancer were identified using bioinformatics analysis. Clinical prognostic and survival analyses were performed to identify genes most negatively associated with these diseases. The top ten compounds with the strongest binding to the target genes were screened from the ChemDiv database using virtual screening technology, considering the blood–brain barrier. Molecular dynamics simulations were used to identify potential sites for the binding of these compounds to the target protein MX1. Additionally, point mutation analysis of the target protein was performed. Finally, the binding site was verified <em>in vitro</em>.</div></div><div><h3>Results</h3><div>The <em>MX1</em> gene was most significantly negatively associated with AD and ovarian cancer. Molecular dynamics simulations revealed intersection sites at Glu-227 and Gly-188, where MX1 binds tightly to the head compound.</div></div><div><h3>Conclusion</h3><div>This study successfully identified <em>MX1</em> as being negatively associated with AD and ovarian cancer and assessed the potential drug compounds that bind most closely to it. Our findings provide important rationale and candidate targets for the development of novel therapeutic strategies for AD and ovarian cancer.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"935 ","pages":"Article 149084"},"PeriodicalIF":2.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes from polarized Microglia: Proteomic insights into potential mechanisms affecting intracerebral hemorrhage","authors":"Yinan Zhou ,&nbsp;Ying Zhang ,&nbsp;Dongchen Xu ,&nbsp;Chenguang Yang ,&nbsp;Xiao Lin ,&nbsp;Kunlin Jin ,&nbsp;Lei Xia ,&nbsp;Qichuan Zhuge ,&nbsp;Su Yang","doi":"10.1016/j.gene.2024.149080","DOIUrl":"10.1016/j.gene.2024.149080","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) is a devastating form of stroke associated with significant morbidity and mortality. Microglia are intracranial innate immune cell that play critical roles in Intracerebral hemorrhage through direct or indirect means. Vesicle transport is a fundamental mechanism of intercellular communication. Recent studies have identified microglia in specific polarized states correlate with pathogenesis, material and signal transmission in ICH through derived extracellular vesicles. Diverse polarization states trigger distinct functions, however, the exosome proteomes across these states remain poorly characterized. Here, we hypothesized that microglia exosomal profiles vary with polarization states, impacting their functional repertoire and influencing outcomes in cerebral hemorrhage. In vitro model of cerebral hemorrhage, administration of 20 μg/ml LPS-induced M1 microglia derived exosomes (M1-Exo) with HT22 enhanced hemin-induced neuronal death, while IL-4-induced M2 microglia derived exosomes (M2-Exo) significantly reduced hemin-induced cell apoptosis and inflammation. Then we identified novel state-specific proteomic profiles of microglia-derived exosomes under these polarization conditions through label-free quantitative mass spectrometry (LFQ-MS). Analysis of protein content identified several exosomal signature proteins and hundreds of differentially expressed proteins across polarization states. Specifically, proteins including UMOD, NLRP3, ACOD1, IL1RN, heme oxygenase 1 (HMOX1), CCL4, and TNFRSF1B in M1-Exo were enriched in inflammatory pathways, while those in M2-Exo exhibited enrichment in autophagy, ubiquitination, and mitochondrial respiration. The analysis of those diverse exosomal proteins suggested unique proteomic profiles and possible intracellular signal transmission and regulation mechanisms. Together, these findings offer new insights and resources for studying microglia-derived exosome and pave the way for the development of novel therapeutic strategies targeting microglial exosome-mediated pathways.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"935 ","pages":"Article 149080"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 65 kilobase deletion of the upstream TYR gene region in a family with oculocutaneous albinism type 1","authors":"Modibo Diallo ,&nbsp;Alicia Defay-Stinat ,&nbsp;Victor Gindensperger ,&nbsp;Angèle Sequeira ,&nbsp;Aurélien Trimouille ,&nbsp;Sophie Javerzat ,&nbsp;Laetitia Bourgeade ,&nbsp;Claudio Plaisant ,&nbsp;Eulalie Lasseaux ,&nbsp;Vincent Michaud ,&nbsp;Isabelle Drumare ,&nbsp;Benoit Arveiler","doi":"10.1016/j.gene.2024.149079","DOIUrl":"10.1016/j.gene.2024.149079","url":null,"abstract":"<div><div>Oculocutaneous albinism type 1 is caused by variants in the <em>TYR</em> (<em>tyrosinase</em>) gene. We describe a family with two affected sibs who inherited the pathogenic missense <em>TYR</em> variant c.1146C &gt; A;p.(Asn382Lys) from their mother and a deletion encompassing 65 kilobase pairs of the upstream region of the gene between hg38 coordinates chr11:89110944 and chr11:89175770, from their father. The deletion likely arose by non-homologous recombination since the regions including the two deletion breakpoints share no sequence homology. The deletion contains a single enhancer element that is homologous to a 5′ <em>Tyr</em> core regulatory element in the mouse. A luciferase reporter assay showed that this element had a positive regulatory activity. This represents to our knowledge the first deletion solely restricted to non-coding upstream sequences of the <em>TYR</em> gene. It is assumed that the deletion down-regulates expression of the <em>TYR</em> gene and is therefore pathogenic, allowing to establish the diagnosis of OCA 1 in the patients. This study underscores the need to extend the search for pathogenic variants to regulatory regions either by whole genome sequencing or by targeted next generation sequencing of a panel including entire genes (exons, introns, flanking sequences) in order to improve the diagnostic rate in patients with albinism.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"935 ","pages":"Article 149079"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}