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。
{"title":"Role of 1,25-dihydroxy vitamin D3 pathway in chronic urticaria: Findings from a hospital-based case-control study","authors":"Fizalah Kawoosa , Tabasum Shafi , Roohi Rasool, Shazia Nazir, Nusrat Kounsar","doi":"10.1016/j.genrep.2024.102093","DOIUrl":"10.1016/j.genrep.2024.102093","url":null,"abstract":"<div><h3>Background</h3><div>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 (<em>VDR</em>) and vitamin D-binding protein (<em>VDBP</em>), alongside the estimation of serum vitamin D and VDBP levels in Chronic Urticaria (CU) patients.</div></div><div><h3>Methods</h3><div>Blood samples were obtained from all participants (<em>n</em> = 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 <em>VDR</em> (rs1544410, rs2228570) and <em>VDBP</em> (rs7041) polymorphisms using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP).</div></div><div><h3>Results</h3><div>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) (<em>p</em>-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, <em>p</em>-value < 0.0001). Additionally, we observed that the ‘G’ and ‘C’ alleles of <em>VDBP</em> rs7041 and <em>VDR</em> rs2228570, respectively, might be a potential risk factor for the progression of CU.</div></div><div><h3>Conclusion</h3><div>This study provides valuable insights into the potential involvement of <em>VDR</em> and <em>VDBP</em> 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.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102093"},"PeriodicalIF":1.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142719665","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}
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.
{"title":"Investigating the Rrelationship between polymorphisms pd1.9 and rs7421861 of PD1 gene with breast cancer","authors":"Mehdi Kakavandi , Mahdi Hassani Bafrani , Javad Amini Mahabadi , Hassan Hassani Bafrani","doi":"10.1016/j.genrep.2024.102096","DOIUrl":"10.1016/j.genrep.2024.102096","url":null,"abstract":"<div><h3>Introduction</h3><div><em>PD1</em> molecule is a regulatory protein in the immune system that is responsible for the negative induction of active T cells. The <em>PD1</em> gene has many single nucleotide polymorphisms. In this study, the association of polymorphisms in the pd1.9 and rs7421861 positions of the <em>PD1</em> gene with breast cancer was investigated in women with breast cancer.</div></div><div><h3>Materials and methods</h3><div>This experimental study was done in healthy (<em>n</em> = 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 <em>PD1</em> gene with the help of PCR-RFLP technique. Data analysis was done by SPSS software version 19.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>The results showed that polymorphism of pd1.9 and rs7421861 in <em>PD1</em> 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.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102096"},"PeriodicalIF":1.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700813","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}
Pub Date : 2024-11-20DOI: 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.
{"title":"In-silico analysis of XRCC5 non-synonymous single nucleotide polymorphisms (nsSNPs) in acute myeloid leukemia prognosis","authors":"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","doi":"10.1016/j.genrep.2024.102090","DOIUrl":"10.1016/j.genrep.2024.102090","url":null,"abstract":"<div><div>The X-ray repair cross-complementing 5 (<em>XRCC5</em>) 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 <em>XRCC5</em> gene, potentially impacting protein function and influencing cancer progression. We utilized several computational methods to examine potential harmful nsSNPs within the human <em>XRCC5</em> gene to understand their influence on protein structure and function. Out of 412 missense variants, the 42 missense and somatic nsSNPs identified in the <em>XRCC5</em> 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 <em>XRCC5</em> 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 <em>XRCC5</em> 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 <em>XRCC5</em> gene expression significantly impact the survival rates of patients across various cancer types. Finally, the study found two highly deleterious nsSNPs in the <em>XRCC5</em> protein that can be helpful for further proteomic and genomic studies for disease diagnosis and treatment.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102090"},"PeriodicalIF":1.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142719664","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}
Pub Date : 2024-11-20DOI: 10.1016/j.genrep.2024.102097
Aditi Dwivedi , KiranKumar P. Suthar , Rasmieh Hamid , Komal G. Lakhani , Diwakar Singh , Sushil Kumar , Rajkumar B K , Vijay Vekariya , Praveen Prajapat
Drought is a major environmental challenge that affects the quality and yield of cotton fibres. The aim of the present study was to develop drought-responsive EST-SSRs from cotton transcriptome data. A total of 1946 functionally annotated EST-SSR markers were developed, with tri-nucleotide SSR repeats being the most abundant (40.7 %), followed by di-nucleotides (18.1 %). Gene Ontology (GO) associated with EST-SSR showed the presence of genes related to drought stress, such as PIP, CDK, LEA, etc. A set of 46 EST-SSRs was validated under In-vitro conditions on fourteen cotton genotypes, and 15 EST-SSRs were found to be polymorphic. The polymorphic EST-SSRs markers amplified a total of 44 loci with 32.6 % polymorphism. Genetic analysis revealed that the markers NAU-G-16, NAU-G-39, NAU-G-117 and NAU-G-142 amplified four unique alleles at 121, 163, 224 and 238 bp, respectively, only in drought-tolerant cotton genotypes. The effectiveness of the markers was demonstrated by their high polymorphism information content (PIC), which ranged from 0.35 to 0.89. The large number of markers, 60 %, had a PIC value of >0.6 and were classified as highly informative. The genetic similarity coefficients between cotton genotypes ranged from 0.409 to 0.89, indicating moderate genetic diversity. The Shannon index ranged from 0.21 to 0.65, while the Nei coefficient ranged from 0.12 to 0.46. Clustering and PCo analysis showed the distribution of genotypes into four main clusters, with drought-tolerant genotypes grouped into a single cluster. These drought-responsive markers are promising for the further development of marker-assisted breeding with the aim of increasing the productivity of cotton under drought-prone conditions.
{"title":"Exploitation of novel drought responsive EST-SSR markers in tetraploid cotton (Gossypium hirsutum L.)","authors":"Aditi Dwivedi , KiranKumar P. Suthar , Rasmieh Hamid , Komal G. Lakhani , Diwakar Singh , Sushil Kumar , Rajkumar B K , Vijay Vekariya , Praveen Prajapat","doi":"10.1016/j.genrep.2024.102097","DOIUrl":"10.1016/j.genrep.2024.102097","url":null,"abstract":"<div><div>Drought is a major environmental challenge that affects the quality and yield of cotton fibres. The aim of the present study was to develop drought-responsive EST-SSRs from cotton transcriptome data. A total of 1946 functionally annotated EST-SSR markers were developed, with tri-nucleotide SSR repeats being the most abundant (40.7 %), followed by di-nucleotides (18.1 %). Gene Ontology (GO) associated with EST-SSR showed the presence of genes related to drought stress, such as PIP, CDK, LEA, <em>etc.</em> A set of 46 EST-SSRs was validated under <em>In-vitro</em> conditions on fourteen cotton genotypes, and 15 EST-SSRs were found to be polymorphic. The polymorphic EST-SSRs markers amplified a total of 44 loci with 32.6 % polymorphism. Genetic analysis revealed that the markers NAU-G-16, NAU-G-39, NAU-G-117 and NAU-G-142 amplified four unique alleles at 121, 163, 224 and 238 bp, respectively, only in drought-tolerant cotton genotypes. The effectiveness of the markers was demonstrated by their high polymorphism information content (PIC), which ranged from 0.35 to 0.89. The large number of markers, 60 %, had a PIC value of >0.6 and were classified as highly informative. The genetic similarity coefficients between cotton genotypes ranged from 0.409 to 0.89, indicating moderate genetic diversity. The Shannon index ranged from 0.21 to 0.65, while the Nei coefficient ranged from 0.12 to 0.46. Clustering and PCo analysis showed the distribution of genotypes into four main clusters, with drought-tolerant genotypes grouped into a single cluster. These drought-responsive markers are promising for the further development of marker-assisted breeding with the aim of increasing the productivity of cotton under drought-prone conditions.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102097"},"PeriodicalIF":1.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700805","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}
Pub Date : 2024-11-19DOI: 10.1016/j.genrep.2024.102094
Marykutty Thomas , Jinty Sukumaran , P.M. Rojan , R. Thirupathy Venkatachalapathy , T.V. Aravindakshan , J. Saalom King , M.R. Akhila
Beetal goats, the second largest Indian goat breed, are known for their adaptation to hot arid tropical climates. Beyond their phylogenetic significance, recent evidence suggests that mitogenome modifications play a crucial role in the adaptation of animals to environmental stress factors. This study aims to characterize the mitogenome of Beetal goats at the molecular level, elucidate their mitogenomic adaptations and determine the maternal phylogenetic status of Indian Beetal goats. Whole genome sequencing of pooled DNA samples from five unrelated Beetal goats was carried out to obtain mitogenome sequence. The Beetal goat mitogenome comprised of a coding region with 37 genes: 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), and two ribosomal RNAs (rRNAs), as well as a non-coding hypervariable displacement loop (D-loop) region. We identified nine SNPs inclusive of seven synonymous and two nonsynonymous ones located in PCGs that too in respiratory complex I subunit genes, five of which were novel. Two nonsynonymous SNPs (10,229 A > G in ND4 and 13,964 G > A in ND6) were homoplasmic ones with marked influence on their mRNA and protein structures. Synonymous SNPs influenced the minimum free energy (MFE) and topology of predicted mRNA secondary structures, thereby affecting mRNA stability and translation efficiency. Phylogenetic analysis of the D-loop region classified Beetal goats into haplogroup B. Mitogenome analysis of Beetal goats, in comparison with other goat populations revealed the greatest genetic similarity to Southeast Asian goats. The comprehensive analysis of mitochondrial DNA in Beetal goats reveals significant genetic adaptations crucial for their survival in hot, arid environments. This study also highlights the complex matrilineal origins of Beetal goats.
Beetal山羊是印度第二大山羊品种，以适应炎热干旱的热带气候而闻名。除了其系统发育意义之外，最近的证据表明，有丝分裂基因组的修饰在动物适应环境胁迫因素方面起着至关重要的作用。本研究旨在从分子水平描述比塔尔山羊有丝分裂基因组的特征，阐明其有丝分裂基因组的适应性，并确定印度比塔尔山羊的母系系统发育状况。对来自五只无亲缘关系的比达山羊的DNA样本进行了全基因组测序，以获得有丝分裂基因组序列。比达山羊有丝分裂基因组由一个包含 37 个基因的编码区组成：22 个转运核糖核酸（tRNA）、13 个蛋白质编码基因（PCG）和 2 个核糖体核糖核酸（rRNA），以及一个非编码超变异位移环（D-loop）区。我们发现了 9 个 SNPs，包括 7 个同义 SNPs 和 2 个非同义 SNPs，它们位于 PCGs 中的呼吸复合体 I 亚基基因中，其中 5 个是新发现的。两个非同义 SNP（ND4 中的 10,229 个 A > G 和 ND6 中的 13,964 个 G > A）是同质的，对其 mRNA 和蛋白质结构有显著影响。同义 SNP 影响了预测的 mRNA 二级结构的最小自由能（MFE）和拓扑结构，从而影响了 mRNA 的稳定性和翻译效率。与其他山羊种群相比，Beetal 山羊的线粒体基因组分析显示其与东南亚山羊的遗传相似性最大。对 Beetal 山羊线粒体 DNA 的全面分析揭示了它们在炎热、干旱环境中生存的重要遗传适应性。这项研究还突显了贝塔尔山羊复杂的母系起源。
{"title":"Mitogenome based adaptations and phylogeny of Beetal goats in India","authors":"Marykutty Thomas , Jinty Sukumaran , P.M. Rojan , R. Thirupathy Venkatachalapathy , T.V. Aravindakshan , J. Saalom King , M.R. Akhila","doi":"10.1016/j.genrep.2024.102094","DOIUrl":"10.1016/j.genrep.2024.102094","url":null,"abstract":"<div><div>Beetal goats, the second largest Indian goat breed, are known for their adaptation to hot arid tropical climates. Beyond their phylogenetic significance, recent evidence suggests that mitogenome modifications play a crucial role in the adaptation of animals to environmental stress factors. This study aims to characterize the mitogenome of Beetal goats at the molecular level, elucidate their mitogenomic adaptations and determine the maternal phylogenetic status of Indian Beetal goats. Whole genome sequencing of pooled DNA samples from five unrelated Beetal goats was carried out to obtain mitogenome sequence. The Beetal goat mitogenome comprised of a coding region with 37 genes: 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), and two ribosomal RNAs (rRNAs), as well as a non-coding hypervariable displacement loop (D-loop) region. We identified nine SNPs inclusive of seven synonymous and two nonsynonymous ones located in PCGs that too in respiratory complex I subunit genes, five of which were novel. Two nonsynonymous SNPs (10,229 A > G in <em>ND4</em> and 13,964 G > A in <em>ND6</em>) were homoplasmic ones with marked influence on their mRNA and protein structures. Synonymous SNPs influenced the minimum free energy (MFE) and topology of predicted mRNA secondary structures, thereby affecting mRNA stability and translation efficiency. Phylogenetic analysis of the D-loop region classified Beetal goats into haplogroup B. Mitogenome analysis of Beetal goats, in comparison with other goat populations revealed the greatest genetic similarity to Southeast Asian goats. The comprehensive analysis of mitochondrial DNA in Beetal goats reveals significant genetic adaptations crucial for their survival in hot, arid environments. This study also highlights the complex matrilineal origins of Beetal goats.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102094"},"PeriodicalIF":1.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703070","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}
Pub Date : 2024-11-19DOI: 10.1016/j.genrep.2024.102092
Yaser Rafiq Mir , Ashish Kumar Agrahari , Abhishek Choudhary , Asima Hassan , Atul Kumar Taneja , Juan C. Zenteno , Luis Montes-Almanza , Marta Rusmini , Kazunori Namba , Aaqib Zaffar Banday , Raja A.H. Kuchay
Glutaric Aciduria Type 1 (GA1) is a rare autosomal recessive metabolic disorder caused by mutations in the gene GCDH, leading to deficiency of the enzyme glutarylCoA dehydrogenase. This study reports a case of GA1 in a 3-year-old male from Jammu and Kashmir, India, presenting with a compound heterozygous mutation in the GCDH. Whole exome sequencing (WES) and molecular dynamics simulations were employed to investigate the genetic and structural basis of GA1 in the proband. Clinical evaluation, MRI, and tandem mass spectrometry were conducted to assess the patient's metabolic profile and neurological status. The pathogenic impact of the identified mutations (c.881G > A; p.Arg294Gln and c.481C > T; p.Arg161Trp) was analyzed using computational tools and molecular dynamics simulations. Molecular dynamics simulations indicated significant dynamic changes in the mutant protein structures. The R161W mutation increased flexibility, while the R294Q mutation caused notable conformational instability at the catalytic site, reducing its normal protein function and stability. The RMSD, RMSF, and SASA analyses supported these findings, correlating well with experimental observations. The molecular dynamics simulations provided valuable insights into the structural implications of the R161W and R294Q mutations and might contribute to a deeper understanding of GA1 molecular mechanisms.
{"title":"Exome sequencing and molecular dynamics simulation characterizes a compound heterozygous GCDH missense variant leading to glutaric aciduria type 1 in a paediatric patient from Jammu and Kashmir, India","authors":"Yaser Rafiq Mir , Ashish Kumar Agrahari , Abhishek Choudhary , Asima Hassan , Atul Kumar Taneja , Juan C. Zenteno , Luis Montes-Almanza , Marta Rusmini , Kazunori Namba , Aaqib Zaffar Banday , Raja A.H. Kuchay","doi":"10.1016/j.genrep.2024.102092","DOIUrl":"10.1016/j.genrep.2024.102092","url":null,"abstract":"<div><div>Glutaric Aciduria Type 1 (GA1) is a rare autosomal recessive metabolic disorder caused by mutations in the gene GCDH, leading to deficiency of the enzyme glutarylCoA dehydrogenase. This study reports a case of GA1 in a 3-year-old male from Jammu and Kashmir, India, presenting with a compound heterozygous mutation in the GCDH. Whole exome sequencing (WES) and molecular dynamics simulations were employed to investigate the genetic and structural basis of GA1 in the proband. Clinical evaluation, MRI, and tandem mass spectrometry were conducted to assess the patient's metabolic profile and neurological status. The pathogenic impact of the identified mutations (c.881G > A; p.Arg294Gln and c.481C > T; p.Arg161Trp) was analyzed using computational tools and molecular dynamics simulations. Molecular dynamics simulations indicated significant dynamic changes in the mutant protein structures. The R161W mutation increased flexibility, while the R294Q mutation caused notable conformational instability at the catalytic site, reducing its normal protein function and stability. The RMSD, RMSF, and SASA analyses supported these findings, correlating well with experimental observations. The molecular dynamics simulations provided valuable insights into the structural implications of the R161W and R294Q mutations and might contribute to a deeper understanding of GA1 molecular mechanisms.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102092"},"PeriodicalIF":1.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700811","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}
Autoimmune thyroid diseases (AITDs), such as hypothyroidism, result from an intricate combination of genetic and environmental influences. The relationship between genetic variations in the MTHFR and TNFSF4 genes and autoimmune illnesses has been established, but their impact on hypothyroidism has not been well investigated. This study examines the associations between specific polymorphisms in the MTHFR (rs1801133) and TNFSF4 (rs3850641 and rs7514229) genes and the risk of hypothyroidism.
Methods
The study involved 168 hypothyroid patients and 171 healthy controls, all female and aged 18 to 45, from the Department of Obstetrics and Gynecology, Chettinad Academy of Research and Education in Chennai, India. Exclusion criteria included autoimmune thyroid diseases, pregnancy, medication use, and HIV positivity. Literature from PubMed, Cochrane Library, and Google Scholar, published between 2010 and 2024, was reviewed. Keywords included ‘MTHFR,’ ‘gene,’ ‘rs1801133,’ ‘AITD,’ and ‘Hypothyroidism.’ Heterogeneity was assessed using I² statistics, and the fixed or random effects model was applied accordingly. Sensitivity and publication bias were evaluated through various tests.
Results
The GA genotype and A allele were associated with increased hypothyroidism risk (OR = 0.55, 95 % CI: 0.35–0.89; OR = 0.62, 95 % CI: 0.40–0.94). The AA genotype did not significantly affect the MTHFR rs1801133 polymorphism. The G allele was associated with reduced hypothyroidism risk (OR = 0.67, 95 % CI: 0.47–0.97). No significant effects were found for genotype distributions or genetic models in TNFSF4 rs3850641, whereas the TNFSF4 rs7514229 polymorphism, the GT genotype, and the T allele were associated with reduced hypothyroidism risk (OR = 0.46, 95 % CI: 0.23–0.92; OR = 0.48, 95 % CI: 0.25–0.94). The dominant model revealed an elevated risk with GT+TT genotypes, and in the MTHFR rs1801133 polymorphism, the allelic model showed a significant link with hypothyroidism (OR = 1.49, 95 % CI: 0.99–2.22), while other genetic models did not demonstrate persistent significant correlations. A high degree of heterogeneity was identified.
Conclusion
The research discovered a strong correlation, particularly in the GA genotype and A allele, between the MTHFR rs1801133 polymorphism and the risk of hypothyroidism. Although some TNFSF4 polymorphisms showed associations with hypothyroidism, their overall impact was modest. Future research should include more significant, more diverse populations to understand better these genetic risk factors and their implications for hypothyroidism prevention and management.
{"title":"Genetic predisposition of MTHFR and TNFSF4 gene polymorphism related to hypothyroidism– A meta-analysis","authors":"Iyshwarya Bhaskar Kalarani , Karpagavel Lakshmanan , Ramakrishnan Veerabathiran","doi":"10.1016/j.genrep.2024.102091","DOIUrl":"10.1016/j.genrep.2024.102091","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune thyroid diseases (AITDs), such as hypothyroidism, result from an intricate combination of genetic and environmental influences. The relationship between genetic variations in the MTHFR and TNFSF4 genes and autoimmune illnesses has been established, but their impact on hypothyroidism has not been well investigated. This study examines the associations between specific polymorphisms in the MTHFR (rs1801133) and TNFSF4 (rs3850641 and rs7514229) genes and the risk of hypothyroidism.</div></div><div><h3>Methods</h3><div>The study involved 168 hypothyroid patients and 171 healthy controls, all female and aged 18 to 45, from the Department of Obstetrics and Gynecology, Chettinad Academy of Research and Education in Chennai, India. Exclusion criteria included autoimmune thyroid diseases, pregnancy, medication use, and HIV positivity. Literature from PubMed, Cochrane Library, and Google Scholar, published between 2010 and 2024, was reviewed. Keywords included ‘MTHFR,’ ‘gene,’ ‘rs1801133,’ ‘AITD,’ and ‘Hypothyroidism.’ Heterogeneity was assessed using I² statistics, and the fixed or random effects model was applied accordingly. Sensitivity and publication bias were evaluated through various tests.</div></div><div><h3>Results</h3><div>The GA genotype and A allele were associated with increased hypothyroidism risk (OR = 0.55, 95 % CI: 0.35–0.89; OR = 0.62, 95 % CI: 0.40–0.94). The AA genotype did not significantly affect the MTHFR rs1801133 polymorphism. The G allele was associated with reduced hypothyroidism risk (OR = 0.67, 95 % CI: 0.47–0.97). No significant effects were found for genotype distributions or genetic models in TNFSF4 rs3850641, whereas the TNFSF4 rs7514229 polymorphism, the GT genotype, and the T allele were associated with reduced hypothyroidism risk (OR = 0.46, 95 % CI: 0.23–0.92; OR = 0.48, 95 % CI: 0.25–0.94). The dominant model revealed an elevated risk with GT+TT genotypes, and in the MTHFR rs1801133 polymorphism, the allelic model showed a significant link with hypothyroidism (OR = 1.49, 95 % CI: 0.99–2.22), while other genetic models did not demonstrate persistent significant correlations. A high degree of heterogeneity was identified.</div></div><div><h3>Conclusion</h3><div>The research discovered a strong correlation, particularly in the GA genotype and A allele, between the MTHFR rs1801133 polymorphism and the risk of hypothyroidism. Although some TNFSF4 polymorphisms showed associations with hypothyroidism, their overall impact was modest. Future research should include more significant, more diverse populations to understand better these genetic risk factors and their implications for hypothyroidism prevention and management.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102091"},"PeriodicalIF":1.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703073","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}
Pub Date : 2024-11-19DOI: 10.1016/j.genrep.2024.102087
Rajni Kumari , Ratna Prabha , Pradeep K. Ray , S. Dayal , Golla Thirupathi Rao , Reena Kumari Kamal , P.C. Chandran , A. Dey , Jyoti Kumar , M.K. Tripathi , Sanjay Kumar , Kamal Sarma
The Maithili duck breeds are indigenous to southern Asia and hold significant socioeconomic value for duck farmers in India. Though, they face endangerment primarily due to unregulated crossbreeding practices. Present study aimed to characterize the whole mitochondrial genome of the Maithili duck (Anas platyrhynchos, Anseriformes), which is still unexplored. This is first report about sequencing and annotation of full length mitochondrial DNA (mtDNA) of the Maithili duck, revealing a size of 16,607 bp. Thirteen protein-coding genes (PCGs), several ribosomal RNA (rRNA) genes, twenty three transfer RNA (tRNA) genes and a prominent non-coding control region (D-loop) were present in the mtDNA. The initiation codon for each PCG was ATG, except for ND1 (ACA), ND5 (GTG), and COX2 (GTG). Among the 13 PCGs, six terminated with the typical single T-- codon, while the rest ended with TAA, CAA, AGG, and TAG. Moreover, these 13 PCGs' relative synonymous codon usage matched quite well with previous published Anseriformes genomes. Every tRNA gene showed normal secondary structures of a clover-leaf, except for tRNA-Ser (GCT), which did not have the dihydrouridine 'DHU' arm. Phylogenetic analysis positioned the Maithili duck breed in close relation to the mallard breed of Anas platyrhynchos. With the entire mitochondrial genome sequence now available, researchers will find it easier to investigate the evolutionary links between ducks and other bird species and trace the history of domestication.
{"title":"Molecular characterization and sequencing of the whole mitochondrial genome of native duck breed Maithili (Anas platyrhynchos)","authors":"Rajni Kumari , Ratna Prabha , Pradeep K. Ray , S. Dayal , Golla Thirupathi Rao , Reena Kumari Kamal , P.C. Chandran , A. Dey , Jyoti Kumar , M.K. Tripathi , Sanjay Kumar , Kamal Sarma","doi":"10.1016/j.genrep.2024.102087","DOIUrl":"10.1016/j.genrep.2024.102087","url":null,"abstract":"<div><div>The Maithili duck breeds are indigenous to southern Asia and hold significant socioeconomic value for duck farmers in India. Though, they face endangerment primarily due to unregulated crossbreeding practices. Present study aimed to characterize the whole mitochondrial genome of the Maithili duck (Anas platyrhynchos, Anseriformes), which is still unexplored. This is first report about sequencing and annotation of full length mitochondrial DNA (mtDNA) of the Maithili duck, revealing a size of 16,607 bp. Thirteen protein-coding genes (PCGs), several ribosomal RNA (rRNA) genes, twenty three transfer RNA (tRNA) genes and a prominent non-coding control region (D-loop) were present in the mtDNA. The initiation codon for each PCG was ATG, except for ND1 (ACA), ND5 (GTG), and COX2 (GTG). Among the 13 PCGs, six terminated with the typical single T-- codon, while the rest ended with TAA, CAA, AGG, and TAG. Moreover, these 13 PCGs' relative synonymous codon usage matched quite well with previous published Anseriformes genomes. Every tRNA gene showed normal secondary structures of a clover-leaf, except for tRNA-Ser (GCT), which did not have the dihydrouridine 'DHU' arm. Phylogenetic analysis positioned the Maithili duck breed in close relation to the mallard breed of Anas platyrhynchos. With the entire mitochondrial genome sequence now available, researchers will find it easier to investigate the evolutionary links between ducks and other bird species and trace the history of domestication.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102087"},"PeriodicalIF":1.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703072","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}
Pub Date : 2024-11-15DOI: 10.1016/j.genrep.2024.102088
Nima Nikbin Kavishahi , Seyed Mostafa Shiryazdi , Farimah Shamsi , Ali Dadbinpour , Mahta Mazaheri
Background
The level of hormones and genetic predispositions increase the risk of breast cancer. Genetic variations in the genes of the telomere pathway, which can influence the activity of telomerase, may be decisive for the development of breast cancer. Due to a lack of studies on TERT gene polymorphisms (rs2736100 and rs2736109) in the Iranian population, in this study we investigated the association of these polymorphisms with breast cancer in the Iranian population.
Patients & methods
A total of 300 individuals participated in this research, which included 150 breast cancer patients and 150 healthy controls. Participants' blood samples were collected before the beginning of treatment. The RFLP-PCR procedure was used for the genotyping of TERT gene rs2736109 and rs2736100 polymorphisms.
Results
There are statistically significant differences in the age of menarche and the age of menopause (P-value <0.05). For rs2736100, the frequency of TT genotype in the case and control groups was 22.7 % and 16.7 %, respectively. However, these differences were not statistically significant (P-value >0.05). For rs2736109, the frequency of the AA genotype was lower in the case group (12.0 % vs. 19.3 %). These differences reach a statistically significant level (P-value = 0.012). Individuals carrying AA genotype have a lower risk of suffering from breast cancer (odds ratio = 0.403, 95 % CI: 0.196–0.827).
Conclusion
Our findings suggest that the rs27326109 polymorphism in the TERT gene is associated with a decreased risk of breast cancer. Also this study reveals that age of menarche and age of menopause are associated with risk of this disease.
{"title":"Association between TERT gene polymorphisms (rs2736100 and rs2736109) and breast cancer risk in the Iranian population: A case-control study","authors":"Nima Nikbin Kavishahi , Seyed Mostafa Shiryazdi , Farimah Shamsi , Ali Dadbinpour , Mahta Mazaheri","doi":"10.1016/j.genrep.2024.102088","DOIUrl":"10.1016/j.genrep.2024.102088","url":null,"abstract":"<div><h3>Background</h3><div>The level of hormones and genetic predispositions increase the risk of breast cancer. Genetic variations in the genes of the telomere pathway, which can influence the activity of telomerase, may be decisive for the development of breast cancer. Due to a lack of studies on <em>TERT</em> gene polymorphisms (rs2736100 and rs2736109) in the Iranian population, in this study we investigated the association of these polymorphisms with breast cancer in the Iranian population.</div></div><div><h3>Patients & methods</h3><div>A total of 300 individuals participated in this research, which included 150 breast cancer patients and 150 healthy controls. Participants' blood samples were collected before the beginning of treatment. The RFLP-PCR procedure was used for the genotyping of <em>TERT</em> gene rs2736109 and rs2736100 polymorphisms.</div></div><div><h3>Results</h3><div>There are statistically significant differences in the age of menarche and the age of menopause (<em>P</em>-value <0.05). For rs2736100, the frequency of TT genotype in the case and control groups was 22.7 % and 16.7 %, respectively. However, these differences were not statistically significant (<em>P</em>-value >0.05). For rs2736109, the frequency of the AA genotype was lower in the case group (12.0 % vs. 19.3 %). These differences reach a statistically significant level (P-value = 0.012). Individuals carrying AA genotype have a lower risk of suffering from breast cancer (odds ratio = 0.403, 95 % CI: 0.196–0.827).</div></div><div><h3>Conclusion</h3><div>Our findings suggest that the rs27326109 polymorphism in the TERT gene is associated with a decreased risk of breast cancer. Also this study reveals that age of menarche and age of menopause are associated with risk of this disease.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102088"},"PeriodicalIF":1.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703074","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}
Pub Date : 2024-11-14DOI: 10.1016/j.genrep.2024.102089
Sunil Epuri, Dudi Nikitha, Kalyan Ram Uppaluri, Hima Jyothi Challa, Kalyani Palasamudram, Vrushabh Anil Nikhade, K. Sri Manjari
A woman with a prior diagnosis of thyroid dysfunction was found to have hyperprolactinemia and incidental hypercalcemia. Further investigation led to the diagnosis of a parathyroid adenoma. The unique constellation of hormonal abnormalities and multifocal thyroid nodules defied explanation by known MEN syndromes (no family history). We report the identification of a heterozygous p.Val109Gly mutation in CDKN1B, a gene associated with MEN4 syndrome, through targeted genetic testing. The presented case expands the phenotypic spectrum of MEN4 and highlights the utility of genetic testing in diagnosing syndromic forms of endocrine hyperplasias.
{"title":"Unveiling a rare endocrine puzzle: A case of CDKN1B mutation-associated MEN4 syndrome","authors":"Sunil Epuri, Dudi Nikitha, Kalyan Ram Uppaluri, Hima Jyothi Challa, Kalyani Palasamudram, Vrushabh Anil Nikhade, K. Sri Manjari","doi":"10.1016/j.genrep.2024.102089","DOIUrl":"10.1016/j.genrep.2024.102089","url":null,"abstract":"<div><div>A woman with a prior diagnosis of thyroid dysfunction was found to have hyperprolactinemia and incidental hypercalcemia. Further investigation led to the diagnosis of a parathyroid adenoma. The unique constellation of hormonal abnormalities and multifocal thyroid nodules defied explanation by known MEN syndromes (no family history). We report the identification of a heterozygous p.Val109Gly mutation in <em>CDKN1B</em>, a gene associated with MEN4 syndrome, through targeted genetic testing. The presented case expands the phenotypic spectrum of MEN4 and highlights the utility of genetic testing in diagnosing syndromic forms of endocrine hyperplasias.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102089"},"PeriodicalIF":1.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703075","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}
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