Gene Reports最新文献_第6页

Genetic interactions and co-operating effects of non-HSA21 genes on the phenotypic variability in Down syndrome

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-12-03 DOI: 10.1016/j.genrep.2024.102106

Bani Bandana Ganguly, Nitin N. Kadam

Trisomy 21 (T21) defines the complex characteristics of Down syndrome (DS). However, enormous variation has been documented in the multifarious features of the syndrome, regardless of full or partial T21 among individuals with DS. Individual variability exists in degree of manifestation for each subset of the DS-features, especially intellectual disability, characteristic facial/physical dysmorphology, a hypocellular brain, and Alzheimer's disease (AD), though constitutively present in all DS. A small segment in the chromosome 21 (HSA21) was designated as the Down Syndrome Critical Region (DSCR) responsible for defining DS characteristics; however, DSCR dogma has been challenged due to variability in penetrance and expressivity of DS-phenotypes. Characterization of genes identified in human DS and recombinant mouse models of DS have postulated that DS-features are not the sole contribution of DSCR genes but the possibility of interaction among non-contiguous genes might exist. Several studies suggested that DSCR region is necessary for some of the DS-phenotypes but not sufficient to produce most of the DS-specific features such as congenital heart defect (DS-CHD) and leukemia. Further, allelic variation, epigenetic and environmental impact and small effects of modifier genes might result in perturbation of genetic homeostasis in subjects with DS. Collectively, the solitary effect of a triplicated gene was demonstrated to be inconspicuous; however, its contribution to trisomic phenotypes was predicted likely in antagonistic or synergistic association with other specific genes. Nevertheless, gene-phenotype association has remained unanswered for complex expression of the DS-phenotypes at the backdrop of trisomic HSA21.

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引用次数: 0

Corrigendum to “Upregulated long non-coding RNAs TMPO-AS1, DDX11-AS1, and POLE gene expression predict poor prognosis in head and neck squamous cell carcinoma (HNSCC)” [Gene Rep. Volume 36, September 2024/101942]

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-12-01 DOI: 10.1016/j.genrep.2024.102095

Mahnoosh Mokhtarinejad , Maryam Pirhoushiaran , Roozbeh Heidarzadehpilehrood , Sara Hesami , Farid Azmoudeh-Ardalan , Abbas Shakoori Farahani

引用次数: 0

Molecular uniqueness and phylogenetic study of Magnaporthe oryzae isolates from Bangladesh

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-11-30 DOI: 10.1016/j.genrep.2024.102103

Muhammad Mahmudul Hasan , Md. Dheeman Tanvir Swakshar , Atiqur Rahman , M.A. Malek , M.A.K. Azad , Most. Maliha Parvin , Md. Hasin Raiyan , Ujjal Kumar Nath , Md. Amirul Alam

Rice blast, induced by the hemibiotrophic fungus Magnaporthe oryzae, poses a significant threat to global rice production, causing substantial yield losses and being particularly prevalent in Bangladesh. This study aimed to explore the mutational dynamics of the rice blast pathogen, influencing the development of disease epidemics, by conducting a phylogenetic analysis. To achieve this, 19 M. oryzae isolates were gathered from four districts in the Sylhet division of Bangladesh. All isolates underwent confirmation as M. oryzae through internal transcribed spacer (ITS) sequence analysis. The phylogenetic analysis revealed a consistent distribution of the 19 blast isolates into three clusters, highlighting substantial genetic variation among isolates from the same location and genetic similarities among isolates from diverse geographical origins. Notably, cluster-B comprised 18 noble blast isolates out of the total 19, suggesting a common origin for these isolates. In contrast, isolates from cluster A and cluster C, specifically W30216962_BN10_ITS5_F12, did not exhibit any noble blast isolates. This finding indicates that all the noble isolates in cluster B shared the same source or originated from the same ancestor. The insights gained from this study hold promise for shaping strategies to enhance disease management against rice blast. These strategies may involve resistance breeding, genetic studies, and a deeper understanding of host-pathogen interactions.

{"title":"Molecular uniqueness and phylogenetic study of Magnaporthe oryzae isolates from Bangladesh","authors":"Muhammad Mahmudul Hasan , Md. Dheeman Tanvir Swakshar , Atiqur Rahman , M.A. Malek , M.A.K. Azad , Most. Maliha Parvin , Md. Hasin Raiyan , Ujjal Kumar Nath , Md. Amirul Alam","doi":"10.1016/j.genrep.2024.102103","DOIUrl":"10.1016/j.genrep.2024.102103","url":null,"abstract":"<div><div>Rice blast, induced by the hemibiotrophic fungus <em>Magnaporthe oryzae</em>, poses a significant threat to global rice production, causing substantial yield losses and being particularly prevalent in Bangladesh. This study aimed to explore the mutational dynamics of the rice blast pathogen, influencing the development of disease epidemics, by conducting a phylogenetic analysis. To achieve this, 19 <em>M. oryzae</em> isolates were gathered from four districts in the Sylhet division of Bangladesh. All isolates underwent confirmation as <em>M. oryzae</em> through internal transcribed spacer (ITS) sequence analysis. The phylogenetic analysis revealed a consistent distribution of the 19 blast isolates into three clusters, highlighting substantial genetic variation among isolates from the same location and genetic similarities among isolates from diverse geographical origins. Notably, cluster-B comprised 18 noble blast isolates out of the total 19, suggesting a common origin for these isolates. In contrast, isolates from cluster A and cluster C, specifically W30216962_BN10_ITS5_F12, did not exhibit any noble blast isolates. This finding indicates that all the noble isolates in cluster B shared the same source or originated from the same ancestor. The insights gained from this study hold promise for shaping strategies to enhance disease management against rice blast. These strategies may involve resistance breeding, genetic studies, and a deeper understanding of host-pathogen interactions.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102103"},"PeriodicalIF":1.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human papillomavirus as a potential etiological factor and biomarker in bladder carcinogenesis: A molecular epidemiological study

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-11-30 DOI: 10.1016/j.genrep.2024.102104

Mouna Aqerrout , Abdelilah Laraqui , Khalid Ennibi , Ahmed Ameur , Larbi Hamedoun , Mohammed Alami , Anouar El Ghazzaly , Moulay Mustapha Ennaji

Bladder cancer is a major public health concern, and the identification of novel biomarkers is crucial for improving its diagnosis and treatment. Human Papillomavirus (HPV) has been linked to various neoplasms, though its relevance to bladder cancer (BC) is hardly known. In this study, we aimed at evaluating the presence of HPV in bladder cancer tissues and determine its utility as a potential biomarker. Nested PCR, using consensus primers MY09/11, GP5+/6+ and reference plasmids targeting HPVs 16, 18, 33, 11, 6 and 31 were employed on 50 samples from patients with bladder carcinoma. Among the 50 bladder cancer patients analyzed, 23 (46 %) tested positive for HPV, while 27 (54 %) tested negative and significant association was identified between HPV infection and key clinical parameters including tumor stage (P = 0.031**), tumor grade (P = 0.007**) and muscle invasion (P = 0.046*). High-risk HPV genotypes, specifically type 16 was the most prevalent and was detected in 11 (47.8 %) of bladder cancer cases. Single HPV infection 18 (78.2 %) was more common than co-infection cases 5 (21.7 %), though no statistical significance was observed between infection type and patients' clinicopathological parameters. Our findings revealed a significant association between HPV infection and advanced tumor characteristics, particularly with higher tumor grade and pathological T-stage. High-risk HPV genotypes, notably types 16 and 18, were the most frequently observed, suggesting a potential role for high-risk HPV subtypes in bladder tumor progression. These findings underscore the possible contribution of HPV in bladder carcinogenesis and suggest that infection with the virus, particularly with high-risk strains, could serve as a valuable biomarker for early bladder cancer diagnosis and risk assessment. Targeting HPV in bladder cancer tissues may thus pave the way for HPV-based diagnostic and prognostic tools and tailored therapeutic approaches.

{"title":"Human papillomavirus as a potential etiological factor and biomarker in bladder carcinogenesis: A molecular epidemiological study","authors":"Mouna Aqerrout , Abdelilah Laraqui , Khalid Ennibi , Ahmed Ameur , Larbi Hamedoun , Mohammed Alami , Anouar El Ghazzaly , Moulay Mustapha Ennaji","doi":"10.1016/j.genrep.2024.102104","DOIUrl":"10.1016/j.genrep.2024.102104","url":null,"abstract":"<div><div>Bladder cancer is a major public health concern, and the identification of novel biomarkers is crucial for improving its diagnosis and treatment. Human Papillomavirus (HPV) has been linked to various neoplasms, though its relevance to bladder cancer (BC) is hardly known. In this study, we aimed at evaluating the presence of HPV in bladder cancer tissues and determine its utility as a potential biomarker. Nested PCR, using consensus primers MY09/11, GP5+/6+ and reference plasmids targeting HPVs 16, 18, 33, 11, 6 and 31 were employed on 50 samples from patients with bladder carcinoma. Among the 50 bladder cancer patients analyzed, 23 (46 %) tested positive for HPV, while 27 (54 %) tested negative and significant association was identified between HPV infection and key clinical parameters including tumor stage (<em>P</em> = 0.031**), tumor grade (<em>P</em> = 0.007**) and muscle invasion (<em>P</em> = 0.046*). High-risk HPV genotypes, specifically type 16 was the most prevalent and was detected in 11 (47.8 %) of bladder cancer cases. Single HPV infection 18 (78.2 %) was more common than co-infection cases 5 (21.7 %), though no statistical significance was observed between infection type and patients' clinicopathological parameters. Our findings revealed a significant association between HPV infection and advanced tumor characteristics, particularly with higher tumor grade and pathological T-stage. High-risk HPV genotypes, notably types 16 and 18, were the most frequently observed, suggesting a potential role for high-risk HPV subtypes in bladder tumor progression. These findings underscore the possible contribution of HPV in bladder carcinogenesis and suggest that infection with the virus, particularly with high-risk strains, could serve as a valuable biomarker for early bladder cancer diagnosis and risk assessment. Targeting HPV in bladder cancer tissues may thus pave the way for HPV-based diagnostic and prognostic tools and tailored therapeutic approaches.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102104"},"PeriodicalIF":1.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phylogenetic annotation and expression analysis of heat shock protein 70 genes in two Henosepilachna species

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-11-29 DOI: 10.1016/j.genrep.2024.102098

Yu-Xing Zhang , Hai-Hui Liu , Jia-Qing Yu , Lin Jin , Kai-Yun Fu , Wen-Chao Guo , Guo-Qing Li

Two Henosepilachna beetles are notorious defoliators mainly attacking potatoes. In China, H. vigintioctopunctata is predominantly distributed in the southern region of the Yangtze River, while H. vigintioctomaculata is found in northern area. In the current paper, we uncovered H. vigintioctopunctata displayed a higher thermotolerance than H. vigintioctomaculata. We identified 15 and 20 full-length heat shock protein 70 (hsp70) genes from H. vigintioctopunctata and H. vigintioctomaculata transcriptomes. A total of 8, 3, 2 and 2 Hvphsp70s in H. vigintioctopunctata, and 6, 9, 2 and 3 Hvmhsp70s in H. vigintioctomaculata fell into cytosolic A (hsp70ca), cytosolic B (hsp70cb), endoplasmic reticulum (hsp70era) and mitochondria (hsp70ma) subfamilies, respectively. Compared with H. vigintioctopunctata, two hspca genes (hspca6 and 7) were absent, whereas hsp70cb subfamily underwent independent expansion, resulting in the generation of 6 new hsp70cb members (Hvmhsp70cb4 to Hvmhsp70cb9) during evolution in H. vigintioctomaculata. Nine H. vigintioctopunctata hsp70s (Hvphsp70ca1-Hvphsp70ca7, Hvphsp70cb1 and Hvphsp70cb2) and 13H. vigintioctomaculata hsp70s (Hvmhsp70ca1-Hvmhsp70ca5, Hvmhsp70cb2, Hvmhsp70cb4-Hvmhsp70cb9 and Hvmhsp70era1) expressionally responded to heat shock, in a species-specific and temperature-dependent manner. Our findings raise a possibility that different members and/or specific compositions of hsp70s may cause thermoresistant disparity between the two Henosepilachna beetles.

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引用次数: 0

Characterization and regulatory analysis of betaine homocysteine S-methyltransferase gene 1 (BHMT1) in mud crab: A gene responsive to salinity and feeding behavior 泥蟹甜菜碱同型半胱氨酸s -甲基转移酶基因1 （BHMT1）的表征及调控分析：一个对盐度和摄食行为敏感的基因

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-11-28 DOI: 10.1016/j.genrep.2024.102102

Jinju Yin , Zhiqiang Liu , Xin Jin , Wei Wang , Lingbo Ma , Ming Zhao

Betaine homocysteine S-methyltransferase gene 1 (BHMT1) encoded betaine homocysteine S-methyltransferase (BHMT) catalyzes the homocysteine-to-methionine reaction using betaine as a methyl donor. Previously, we found that BHMT was lost in the genome of the insect clade of arthropods, but was highly expressed in the mandibular organ (MO) of the mud crab Scylla paramamosain (Sp). To further explore its significance, we performed a primary regulatory analysis of BHMT in mud crabs. The open reading frame (ORF) length of Sp-BHMT1 was 1203 bp, encoding 400 amino acids. Sequence alignment revealed that BHMT1 was highly conserved in different animals, and its identity was higher in more closely related species. Sp-BHMT1 had the highest expression in the MO of both sexes, while its expression in the MO was 1.6-fold higher in males than in females; similar results were also found in the cerebral ganglion, hepatopancreas, and thoracic ganglia tissues. During larval development, Sp-BHMT1 was weakly expressed on most days but was significantly elevated on the first day of the Zoea 2nd (Z2) and Z3 stages. Sp-BHMT1 exhibited the highest expression at a salinity of 10 ‰ and the lowest at a salinity of 30 ‰. With decreasing salinity, the expression of Sp-BHMT1 increased significantly at 6 h and then returned to baseline at 8 h. After starvation treatment, the expression of Sp-BHMT1 was significantly upregulated compared to that in the feed group at all examined time points, with a peak expression at 18:00 on the third day in the starvation group. Krüppel homolog 1 (Kr-h1), a methyl farnesoate (MF) signal gene, could increase Sp-BHMT1 expression under low salinity and starvation, suggesting that a “salinity/starvation→BHMT1 → MF biosynthesis” regulatory axis might exist in crabs. This study provides valuable insights into the functional study of Sp-BHMT1 and MF biosynthetic regulation.

甜菜碱同型半胱氨酸s -甲基转移酶基因1 （BHMT1）编码甜菜碱同型半胱氨酸s -甲基转移酶（BHMT），以甜菜碱为甲基供体催化同型半胱氨酸-蛋氨酸反应。此前，我们发现BHMT在节肢动物昆虫支系的基因组中缺失，但在泥蟹Scylla paramosain （Sp）的下颌器官（MO）中高表达。为了进一步探讨其意义，我们对泥蟹的BHMT进行了初步的调控分析。Sp-BHMT1的开放阅读框长度为1203 bp，编码400个氨基酸。序列比对表明，BHMT1在不同动物中具有高度保守性，在亲缘关系较近的物种中具有较高的同源性。Sp-BHMT1在两性MO中的表达量最高，其在雄性MO中的表达量是雌性MO的1.6倍；在脑神经节、肝胰腺和胸神经节组织中也发现了类似的结果。在幼虫发育过程中，Sp-BHMT1在大部分时间表达较弱，但在Z2和Z3期的第一天表达显著升高。Sp-BHMT1在盐度为10‰时表达量最高，在盐度为30‰时表达量最低。随着盐度的降低，Sp-BHMT1的表达在6 h时显著升高，8 h时恢复到基线水平。饥饿处理后，Sp-BHMT1的表达在所有检测时间点均较饲料组显著上调，饥饿组在第3天18:00达到表达高峰。法诺酸甲酯（methyl farnesoate， MF）信号基因kr ppel同源基因1 （Kr-h1）在低盐度和饥饿条件下可增加Sp-BHMT1的表达，提示蟹体内可能存在“盐度/饥饿→BHMT1→MF生物合成”调控轴。本研究为Sp-BHMT1的功能研究和MF生物合成调控提供了有价值的见解。

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引用次数: 0

Unraveling genetic similarities of Klebsiella pneumoniae from poultry and poultry handlers in Punjab, India

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-11-28 DOI: 10.1016/j.genrep.2024.102101

Neha Parmar , Randhir Singh , Simranpreet Kaur , Anuj Tyagi , Hina Malik , Rabinder Singh Aulakh , Jatinder Paul Singh Gill

The study aimed to characterize K. pneumoniae isolates from poultry (broiler) farms of Ludhiana, Punjab, India. The Whole genome sequencing (WGS) of K. pneumoniae isolates (K. pneumoniae strain PF_L1_IN, K. pneumoniae strain PF_L2_IN, K. pneumoniae strain PHS_IN) using NovaSeq6000 (Illumina, USA) platform revealed the presence of several antimicrobial resistant genes (ARGs) on the genome of the isolates conferring potential resistance to antibiotics classified as critically important, highly important and important. The virulence factors (VFs) detected were Type I fimbriae, Type 3 fimbriae, AcrAB, Aerobactin, Enterobactin, Salmochelin, RcsAB, T6SS-I, II and III. The mobile genetic elements such as plasmid replicons (IncFIB and Col440I), integron elements (In0, CALIN), a unit transposon (Tn512) and insertion sequences (ISKpn24, ISEc9, ISKpn1, IS102, IS903, IS5075 and ISKpn38) were detected in the isolates. The plasmids carried ARGs for the important antibiotic classes such as aminoglycoside, macrolides, quinolones, tetracyclines, carbapenems and sulphonamides. However, none of the insertion sequences and transposons in the isolates was associated with any antimicrobial resistant gene. In multilocus sequence typing (MLST) analysis, the isolates belonged to sequence type (ST) ST-147 and ST-147 with double locus variation, while, in core-genome multilocus sequence typing (cgMLST) the isolates belonged to ST-25590 and ST-1508. The isolates from broiler (K. pneumoniae strain PF_L1_IN) and its handler (K. pneumoniae strain PHS_IN) showed clonal relationship. The present study suggested that the food animal's production environment could act as a reservoir of multidrug resistant (MDR) and Extended spectrum β-lactamases (ESBL) producing K. pneumoniae. These resistant isolates could easily be disseminated to human through shared environment and food.

{"title":"Unraveling genetic similarities of Klebsiella pneumoniae from poultry and poultry handlers in Punjab, India","authors":"Neha Parmar , Randhir Singh , Simranpreet Kaur , Anuj Tyagi , Hina Malik , Rabinder Singh Aulakh , Jatinder Paul Singh Gill","doi":"10.1016/j.genrep.2024.102101","DOIUrl":"10.1016/j.genrep.2024.102101","url":null,"abstract":"<div><div>The study aimed to characterize <em>K. pneumoniae</em> isolates from poultry (broiler) farms of Ludhiana, Punjab, India. The Whole genome sequencing (WGS) of <em>K. pneumoniae</em> isolates (<em>K. pneumoniae</em> strain PF_L1_IN, <em>K. pneumoniae</em> strain PF_L2_IN, <em>K. pneumoniae</em> strain PHS_IN) using NovaSeq6000 (Illumina, USA) platform revealed the presence of several antimicrobial resistant genes (ARGs) on the genome of the isolates conferring potential resistance to antibiotics classified as critically important, highly important and important. The virulence factors (VFs) detected were Type I fimbriae, Type 3 fimbriae, AcrAB, Aerobactin, Enterobactin, Salmochelin, RcsAB, T6SS-I, II and III. The mobile genetic elements such as plasmid replicons (IncFIB and Col440I), integron elements (In0, CALIN), a unit transposon (Tn<em>512</em>) and insertion sequences (ISKpn<em>24</em>, ISEc<em>9</em>, ISKpn<em>1</em>, IS<em>102</em>, IS<em>903</em>, IS<em>5075</em> and ISKpn<em>38</em>) were detected in the isolates. The plasmids carried ARGs for the important antibiotic classes such as aminoglycoside, macrolides, quinolones, tetracyclines, carbapenems and sulphonamides. However, none of the insertion sequences and transposons in the isolates was associated with any antimicrobial resistant gene. In multilocus sequence typing (MLST) analysis, the isolates belonged to sequence type (ST) ST-147 and ST-147 with double locus variation, while, in core-genome multilocus sequence typing (cgMLST) the isolates belonged to ST-25590 and ST-1508. The isolates from broiler (<em>K. pneumoniae</em> strain PF_L1_IN) and its handler (<em>K. pneumoniae</em> strain PHS_IN) showed clonal relationship. The present study suggested that the food animal's production environment could act as a reservoir of multidrug resistant (MDR) and Extended spectrum β-lactamases (ESBL) producing <em>K. pneumoniae</em>. These resistant isolates could easily be disseminated to human through shared environment and food.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102101"},"PeriodicalIF":1.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of 1,25-dihydroxy vitamin D3 pathway in chronic urticaria: Findings from a hospital-based case-control study 1,25-二羟基维生素 D3 途径在慢性荨麻疹中的作用：一项医院病例对照研究的结果

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-11-22 DOI: 10.1016/j.genrep.2024.102093

Fizalah Kawoosa , Tabasum Shafi , Roohi Rasool, Shazia Nazir, Nusrat Kounsar

Background

Previous research has linked dysregulation of the vitamin D pathway to skin diseases. In this study, we sought to explore the genetic variations in the vitamin D receptor (VDR) and vitamin D-binding protein (VDBP), alongside the estimation of serum vitamin D and VDBP levels in Chronic Urticaria (CU) patients.

Methods

Blood samples were obtained from all participants (n = 200) to assess serum vitamin D, VDBP, and total IgE levels using enzyme-linked immunosorbent assay (ELISA). Additionally, DNA was extracted from the blood samples for analysis of VDR (rs1544410, rs2228570) and VDBP (rs7041) polymorphisms using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP).

Results

CU patients exhibited elevated levels of total IgE (208.29 ± 151.293 vs. 125.91 ± 73.13 IU/ml) and VDBP (570.59 ± 158.74 vs. 314.408 ± 140.31 μg/ml) (p-value < 0.0001), as compared to controls. Further, such patients also showed lower vitamin D levels (14.57 ± 8.71 vs. 20.022 ± 8.9 ng/ml, p-value < 0.0001). Additionally, we observed that the ‘G’ and ‘C’ alleles of VDBP rs7041 and VDR rs2228570, respectively, might be a potential risk factor for the progression of CU.

Conclusion

This study provides valuable insights into the potential involvement of VDR and VDBP genetic variants in the pathogenesis of Chronic Urticaria (CU). While no significant associations were observed between these genetic variants and serum levels of vitamin D or VDBP, the identified genetic variations may play a role in increasing CU susceptibility within the Kashmiri population. Further research, including Mendelian randomization studies, is required to confirm any causal relationships.

背景以往的研究表明，维生素 D 途径失调与皮肤病有关。在本研究中，我们试图探讨维生素 D 受体（VDR）和维生素 D 结合蛋白（VDBP）的遗传变异，同时估算慢性荨麻疹（CU）患者的血清维生素 D 和 VDBP 水平。方法从所有参与者（n = 200）中采集血样，使用酶联免疫吸附试验（ELISA）评估血清维生素 D、VDBP 和总 IgE 水平。此外，还从血样中提取 DNA，利用聚合酶链式反应（PCR）和限制性片段长度多态性（RFLP）分析 VDR（rs1544410、rs2228570）和 VDBP（rs7041）多态性。结果与对照组相比，CU 患者的总 IgE（208.29 ± 151.293 vs. 125.91 ± 73.13 IU/ml）和 VDBP（570.59 ± 158.74 vs. 314.408 ± 140.31 μg/ml）水平升高（p 值为 0.0001）。此外，这类患者的维生素 D 水平也较低（14.57 ± 8.71 vs. 20.022 ± 8.9 ng/ml，p 值为 0.0001）。此外，我们还观察到，VDBP rs7041 和 VDR rs2228570 的'G'和'C'等位基因可能是导致慢性荨麻疹恶化的潜在风险因素。虽然在这些遗传变异与血清维生素 D 或 VDBP 水平之间没有观察到明显的关联，但已确定的遗传变异可能会在增加克什米尔人对慢性荨麻疹的易感性方面发挥作用。要确认任何因果关系，还需要进一步的研究，包括孟德尔随机研究。

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引用次数: 0

Investigating the Rrelationship between polymorphisms pd1.9 and rs7421861 of PD1 gene with breast cancer 探讨 PD1 基因多态性 pd1.9 和 rs7421861 与乳腺癌的关系

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-11-20 DOI: 10.1016/j.genrep.2024.102096

Mehdi Kakavandi , Mahdi Hassani Bafrani , Javad Amini Mahabadi , Hassan Hassani Bafrani

Introduction

PD1 molecule is a regulatory protein in the immune system that is responsible for the negative induction of active T cells. The PD1 gene has many single nucleotide polymorphisms. In this study, the association of polymorphisms in the pd1.9 and rs7421861 positions of the PD1 gene with breast cancer was investigated in women with breast cancer.

Materials and methods

This experimental study was done in healthy (n = 110) and breast cancer (n = 110) women. First, 2 ml of blood were taken from groups, and the genome of white blood cells (WBCs) was extracted using a DNA extraction kit. The genotype of samples was determined in pd1.9 and rs7421861 region of PD1 gene with the help of PCR-RFLP technique. Data analysis was done by SPSS software version 19.

Results

The analysis of the data about pd1.9 polymorphism genotypes demonstrated that the frequency of CC genotype in the control group was equal to 92.7 %; while this amount was reported as 80 % in the patient group. Regarding the CT genotype, its frequency was 19.1 % in the patient group, while this rate was 7.3 % in the control group. Also, the data showed that the frequency of TT allele is 0.9 % in the patient group and 0 % in healthy people. In the case of rs7421861, the frequency of TT genotype in the control group was equal to 56.4 %, while this rate was equal to 41.8 % in the patient group. Regarding the CT genotype, its frequency in the patient group was 48.2 %, while this rate was 36.4 % in the control group. The frequency of CC allele is 10 % in the patient group and 7.3 % in healthy people.

Conclusion

The results showed that polymorphism of pd1.9 and rs7421861 in PD1 gene cannot be related to breast cancer. Therefore, determining the genotype of polymorphism in these gene regions will not be useful for screening affected people.

导言PD1 分子是免疫系统中的一种调节蛋白，负责对活性 T 细胞进行负诱导。PD1 基因有许多单核苷酸多态性。本研究调查了乳腺癌妇女 PD1 基因 pd1.9 和 rs7421861 位点的多态性与乳腺癌的关系。首先，各组抽取 2 毫升血液，使用 DNA 提取试剂盒提取白细胞基因组。利用 PCR-RFLP 技术测定样本在 PD1 基因 pd1.9 和 rs7421861 区域的基因型。结果 pd1.9 多态性基因型的数据分析显示，对照组中 CC 基因型的频率为 92.7%，而患者组中这一比例为 80%。至于 CT 基因型，其频率在患者组中为 19.1%，而在对照组中为 7.3%。数据还显示，TT 等位基因在患者组中的频率为 0.9%，而在健康人群中的频率为 0%。就 rs7421861 而言，TT 基因型在对照组中的频率为 56.4%，而在患者组中的频率为 41.8%。至于 CT 基因型，其在患者组中的频率为 48.2%，而在对照组中的频率为 36.4%。结果表明，PD1 基因中的 pd1.9 多态性和 rs7421861 与乳腺癌无关。因此，确定这些基因区域多态性的基因型对筛查患者没有帮助。

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引用次数: 0

In-silico analysis of XRCC5 non-synonymous single nucleotide polymorphisms (nsSNPs) in acute myeloid leukemia prognosis XRCC5 非同义单核苷酸多态性 (nsSNPs) 在急性髓性白血病预后中的内测分析

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-11-20 DOI: 10.1016/j.genrep.2024.102090

Md. Arif Hossen , Md. Arju Hossain , Mohammad Kamruzzaman , Fahim Alam Nobel , Md. Moin Uddin , Md. Tanvir Hossain , Numan Bin Taz , Shahidullah , Tumpa Rani Sarker , Rafia Tabassum Farin , Abdullah Al Noman , Mohammad Nasir Uddin , Mohammod Johirul Islam

The X-ray repair cross-complementing 5 (XRCC5) gene plays a pivotal role in the classical non-homologous end joining (NHEJ) pathway further responding to DNA double-strand breaks. Our study aims to explore harmful non-synonymous single nucleotide polymorphisms (nsSNPs) within the coding region of the XRCC5 gene, potentially impacting protein function and influencing cancer progression. We utilized several computational methods to examine potential harmful nsSNPs within the human XRCC5 gene to understand their influence on protein structure and function. Out of 412 missense variants, the 42 missense and somatic nsSNPs identified in the XRCC5 gene, two (Y316C and R643W) were found to be potentially harmful. Analysis through Project HOPE highlighted significant differences in physicochemical properties, structural changes, and mutations within conserved domains between wild-type and mutant amino acids. Additionally, we identified a methylation site (R486) and phosphorylation sites (318S and 333Y) on the XRCC5 protein using GPS-MSP 1.0 and NetPhos 3.1 servers, respectively. The four pharmacologically significant compounds, CID: 348883 (−9.1 kcal/mol), CID: 376106 (−8.9 kcal/mol), CID: 381764 (−8.8 kcal/mol) and CID: 402650 (−8.7 kcal/mol) demonstrate strong binding affinity to the mutant proteins. Decreased binding affinity to mutant XRCC5 proteins compared to wild-type protein has been determined to influence drug resistance. Besides, molecular dynamics simulation studies demonstrated that the Y316C and R643W mutations are likely to affect the structural integrity of the XRCC5 protein, limiting its capacity to retain correct conformation. Ultimately, examination through the Kaplan-Meier plotter study demonstrated that alterations in XRCC5 gene expression significantly impact the survival rates of patients across various cancer types. Finally, the study found two highly deleterious nsSNPs in the XRCC5 protein that can be helpful for further proteomic and genomic studies for disease diagnosis and treatment.

X 射线修复交叉互补 5（XRCC5）基因在经典的非同源末端连接（NHEJ）途径中发挥着关键作用，进一步应对 DNA 双链断裂。我们的研究旨在探索 XRCC5 基因编码区内有害的非同义单核苷酸多态性（nsSNPs），这些多态性可能会影响蛋白质功能并影响癌症进展。我们利用多种计算方法研究了人类 XRCC5 基因中潜在的有害 nsSNPs，以了解它们对蛋白质结构和功能的影响。在 XRCC5 基因中发现的 412 个错义变异、42 个错义和体细胞 nsSNPs 中，有两个（Y316C 和 R643W）可能是有害的。通过 HOPE 项目进行的分析强调了野生型和突变型氨基酸之间在理化性质、结构变化和保守结构域内突变方面的显著差异。此外，我们还利用 GPS-MSP 1.0 和 NetPhos 3.1 服务器分别确定了 XRCC5 蛋白上的甲基化位点（R486）和磷酸化位点（318S 和 333Y）。CID: 348883 (-9.1 kcal/mol)、CID: 376106 (-8.9 kcal/mol)、CID: 381764 (-8.8 kcal/mol) 和 CID: 402650 (-8.7 kcal/mol)这四种具有药理学意义的化合物显示出与突变蛋白的强大结合亲和力。与野生型蛋白相比，突变型 XRCC5 蛋白的结合亲和力降低已被确定会影响耐药性。此外，分子动力学模拟研究表明，Y316C 和 R643W 突变可能会影响 XRCC5 蛋白的结构完整性，限制其保持正确构象的能力。最后，Kaplan-Meier绘图仪研究表明，XRCC5基因表达的改变会显著影响不同癌症类型患者的生存率。最后，该研究在 XRCC5 蛋白中发现了两个高度有害的 nsSNPs，它们有助于进一步的蛋白质组和基因组研究，从而促进疾病的诊断和治疗。

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引用次数: 0