Single nucleotide polymorphisms (SNPs) in human lactoferrin geneThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin:  Structure, Function and Applications, and has undergone the Journal's usual peer review process.

The lactoferrin protein possesses antimicrobial and antiviral activities. It is also involved in the modulation of the immune response. In a normal healthy individual, lactoferrin plays a role in the front-line host defense against infection and in immune and inflammatory responses. Whether genomic variations, such as single nucleotide polymorphisms (SNPs), have an effect on the structure and function of lactoferrin protein and whether these variations contribute to the different susceptibility of individuals in response to environmental insults are interesting health-related issues. In this study, the lactoferrin gene was resequenced as part of the Environmental Genome Project of the National Institute of Environmental Health Sciences, which operates within the National Institutes of Health. Ninety-one healthy donors of different ethnicities were used to establish common SNPs in the exons of the lactoferrin gene in the general population. The data will serve as a basis from which study the association of lactoferrin polymorphism and disease.

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Seven novel single nucleotide polymorphisms identified within river buffalo (Bubalus bubalis) lactoferrin gene

Tropical Animal Health and Production ◽

10.1007/s11250-009-9516-3 ◽

2009 ◽

Vol 42 (5) ◽

pp. 1021-1026 ◽

Cited By ~ 1

Author(s):

Periasamy Kathiravan ◽

Ranjit S. Kataria ◽

Bishnu P. Mishra ◽

Praveen K. Dubey ◽

M. Selvakumar ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Bubalus Bubalis ◽

River Buffalo ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Lactoferrin Gene

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In Silico Analysis of Non Synonymous Single Nucleotide Polymorphisms (nsSNPs) of SMPX Gene in Hearing Impairment

10.1101/461764 ◽

2018 ◽

Cited By ~ 1

Author(s):

Md. Arifuzzaman ◽

Sarmistha Mitra ◽

Amir Hamza ◽

Raju Das ◽

Nurul Absar ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Protein Stability ◽

In Silico Analysis ◽

Normal Activity ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Binding Motifs ◽

Stability Change ◽

And Function ◽

Dbsnp Database

ABSTRACTBackgroundMutations in SMPX gene can disrupt the normal activity of the SMPX protein which is involved in hearing process.ObjectiveIn this study, deleterious non-synonymous single nucleotide polymorphisms were isolated from the neutral variants by using several bioinformatics tools.MethodFirstly, dbSNP database hosted by NCBI was used to retrieve the SNPs of SMPX gene, secondly, SIFT was used primarily to screen the damaging SNPs. Further, for validation PROVEAN, PredictSNP and PolyPhen 2 were used. I-Mutant 3 was utilized to analyze the protein stability change and MutPred predicted the molecular mechanism of protein stability change. Finally evolutionary conservation was done to study their conservancy by using ConSurf server.ResultsA total of 26 missense (0.6517%) and 3 nonsense variants (0.075%) were retrieved and among them 4 mutations were found deleterious by all the tools of this experiment and are also highly conserved according to ConSurf server. rs772775896, rs759552778, rs200892029 and rs1016314772 are the reference IDs of deleterious mutations where the substitutions are S71L, N19D, A29T and K54N. Loss of Ubiquitination, loss of methylation, loss of glycosylation, and loss of MoRF binding motifs are the root causes of protein stability change.ConclusionThis is the first study regarding nsSNPs of SMPX gene where the most damaging SNPs were screened that are associated with the SMPX gene and can be used for further research to study their effect on protein structure and function, their dynamic behavior and how they actually affect protein’s flexibility.

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Association of MALAT-1 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus

Lupus ◽

10.1177/09612033211040366 ◽

2021 ◽

pp. 096120332110403

Author(s):

Yan-Mei Mao ◽

Yi-Sheng He ◽

Guo-Cui Wu ◽

Yu-Qian Hu ◽

Kun Xiang ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Single Nucleotide Polymorphisms ◽

Lupus Erythematosus ◽

Clinical Characteristics ◽

Clinical Manifestations ◽

Additive Models ◽

Nucleotide Polymorphisms ◽

Systemic Lupus ◽

Single Nucleotide ◽

And Function

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC ( p = 0.036, OR = 0.348, 95% CI: 0.124–0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC ( p = 0.040, OR = 0.355, 95% CI: 0.127–0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

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Sarcopenia, Obesity, and Sarcopenic Obesity: Relationship with Skeletal Muscle Phenotypes and Single Nucleotide Polymorphisms

Journal of Clinical Medicine ◽

10.3390/jcm10214933 ◽

2021 ◽

Vol 10 (21) ◽

pp. 4933

Author(s):

Praval Khanal ◽

Alun G. Williams ◽

Lingxiao He ◽

Georgina K. Stebbings ◽

Gladys L. Onambele-Pearson ◽

...

Keyword(s):

Skeletal Muscle ◽

Single Nucleotide Polymorphisms ◽

Biceps Brachii ◽

Muscle Quality ◽

Sarcopenic Obesity ◽

Gene Variants ◽

Nucleotide Polymorphisms ◽

Obese Women ◽

Single Nucleotide ◽

And Function

Obesity may aggravate the effects of sarcopenia on skeletal muscle structure and function in the elderly, but no study has attempted to identify the gene variants associated with sarcopenia in obese women. Therefore, the aims of the present study were to: (1) describe neuromuscular function in sarcopenic and non-sarcopenic women with or without obesity; (2) identify gene variants associated with sarcopenia in older obese women. In 307 Caucasian women (71 ± 6 years, 66.3 ± 11.3 kg), skeletal muscle mass was estimated using bioelectric impedance, and function was tested with a 30 s one-leg standing-balance test. Biceps brachii thickness and vastus lateralis cross-sectional area (VLACSA) were measured with B-mode ultrasonography. Handgrip strength, maximum voluntary contraction elbow flexion (MVCEF), and knee extension torque (MVCKE) were measured by dynamometry, and MVCKE/VLACSA was calculated. Genotyping was performed for 24 single-nucleotide polymorphisms (SNPs), selected based on their previous associations with muscle-related phenotypes. Based on sarcopenia and obesity thresholds, groups were classified as sarcopenic obese, non-sarcopenic obese, sarcopenic non-obese, or non-sarcopenic non-obese. A two-way analysis of covariance was used to assess the main effects of sarcopenia and obesity on muscle-related phenotypes and binary logistic regression was performed for each SNP to investigate associations with sarcopenia in obesity. There were no significant obesity * sarcopenic status interactions for any of the investigated muscle-related phenotypic parameters. Neither sarcopenia nor obesity had a significant effect on biceps brachii thickness, but sarcopenia was associated with lower VLACSA (p = 0.003). Obesity was associated with lower MVCEF (p = 0.032), MVCKE (p = 0.047), and MVCKE/VLACSA (p = 0.012) with no significant effect of sarcopenia. Adjusted for age and height, three SNPs (ACTN3 rs1815739, MTHFR rs1801131, and MTHFR rs1537516) were associated with sarcopenia in obese participants. Sarcopenia was associated with a smaller muscle size, while obesity resulted in a lower muscle quality irrespective of sarcopenia. Three gene variants (ACTN3 rs1815739, MTHFR rs1801131, and MTHFR rs1537516) suspected to affect muscle function, homocysteine metabolism, or DNA methylation, respectively, were associated with sarcopenia in obese elderly women. Understanding the skeletal muscle features affected by sarcopenia and obesity, and identification of genes related to sarcopenia in obese women, may facilitate early detection of individuals at particular risk of sarcopenic obesity.

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IL1RL1 single nucleotide polymorphisms are associated with asthma in the Iranian population

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2021.1697 ◽

2021 ◽

Author(s):

Maral Ranjbar ◽

Mojdeh Matloubi ◽

Shaghayegh Sadegh ◽

Morteza Fallahpour ◽

Leila Janani ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Genetic Factors ◽

Inflammatory Responses ◽

Interleukin 1 ◽

Positive Association ◽

Iranian Population ◽

Total Serum ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Prick Test

Asthma is a chronic and multifactorial disease which is known to result from environmental and genetic factors. Interleukin 1 receptor-like 1 (IL1RL1) is a receptor, which promotes inflammatory responses after binding to its ligand IL-33. Several studies have shown that IL1RL1 gene polymorphisms are related to susceptibility or protection to asthma. The objective of this study was to evaluate the association between two IL1RL1 single nucleotide polymorphisms (rs10208293 and rs1041973) and the risk of asthma in the Iranian population. We performed genotyping of the IL1RL1 SNPs in 126 adult asthmatics and 300 healthy controls using TaqMan genotyping assay. Moreover, total serum IgE level, eosinophil count, and skin prick test were accomplished. The results indicated that the AA genotype of rs10208293 was positively associated with asthma susceptibility (p=0.028). We did not find any association between rs1041973 and asthma. Overall, our findings indicate that rs10208293 has a positive association with asthma in the Iranian population.

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Faculty Opinions recommendation of Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1156993.617074 ◽

2009 ◽

Author(s):

Bruno Stieger

Keyword(s):

Single Nucleotide Polymorphisms ◽

Bile Salt ◽

Rna Splicing ◽

Messenger Rna ◽

Missense Mutations ◽

Nucleotide Polymorphisms ◽

Bile Salt Export Pump ◽

Single Nucleotide ◽

And Function

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Frequency of single nucleotide polymorphisms of some immune response genes in a population sample from São Paulo, Brazil

Einstein (São Paulo) ◽

10.1590/s1679-45082011ao1866 ◽

2011 ◽

Vol 9 (3) ◽

pp. 359-366

Author(s):

Léa Campos de Oliveira ◽

Rajendranath Ramasawmy ◽

Jaila Dias Borges ◽

Maria Lucia Carnevale Marin ◽

Natalie Guida Muller ◽

...

Keyword(s):

Immune Response ◽

Single Nucleotide Polymorphisms ◽

Inflammatory Responses ◽

Population Sample ◽

Sao Paulo ◽

Genotype Distribution ◽

São Paulo ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Immune Response Genes

ABSTRACT Objective: To present the frequency of single nucleotide polymorphisms of a few immune response genes in a population sample from São Paulo City (SP), Brazil. Methods: Data on allele frequencies of known polymorphisms of innate and acquired immunity genes were presented, the majority with proven impact on gene function. Data were gathered from a sample of healthy individuals, non-HLA identical siblings of bone marrow transplant recipients from the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, obtained between 1998 and 2005. The number of samples varied for each single nucleotide polymorphism analyzed by polymerase chain reaction followed by restriction enzyme cleavage. Results: Allele and genotype distribution of 41 different gene polymorphisms, mostly cytokines, but also including other immune response genes, were presented. Conclusion: We believe that the data presented here can be of great value for case-control studies, to define which polymorphisms are present in biologically relevant frequencies and to assess targets for therapeutic intervention in polygenic diseases with a component of immune and inflammatory responses.

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A survey of proteins encoded by non-synonymous single nucleotide polymorphisms reveals a significant fraction with altered stability and activity

Biochemical Journal ◽

10.1042/bj20090723 ◽

2009 ◽

Vol 424 (1) ◽

pp. 15-26 ◽

Cited By ~ 31

Author(s):

Abdellah Allali-Hassani ◽

Gregory A. Wasney ◽

Irene Chau ◽

Bum Soo Hong ◽

Guillermo Senisterra ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Three Dimensional ◽

Catalytic Efficiency ◽

Nucleotide Polymorphisms ◽

Wild Type ◽

Coding Region ◽

Wild Type Enzyme ◽

Single Nucleotide ◽

The Stability ◽

And Function

On average, each human gene has approximately four SNPs (single nucleotide polymorphisms) in the coding region, half of which are nsSNPs (non-synonymous SNPs) or missense SNPs. Current attention is focused on those that are known to perturb function and are strongly linked to disease. However, the vast majority of SNPs have not been investigated for the possibility of causing disease. We set out to assess the fraction of nsSNPs that encode proteins that have altered stability and activity, for this class of variants would be candidates to perturb cellular function. We tested the thermostability and, where possible, the catalytic activity for the most common variant (wild-type) and minor variants (total of 46 SNPs) for 16 human enzymes for which the three-dimensional structures were known. There were significant differences in the stability of almost half of the variants (48%) compared with their wild-type counterparts. The catalytic efficiency of approx. 14 variants was significantly altered, including several variants of human PKM2 (pyruvate kinase muscle 2). Two PKM2 variants, S437Y and E28K, also exhibited changes in their allosteric regulation compared with the wild-type enzyme. The high proportion of nsSNPs that affect protein stability and function, albeit subtly, underscores the need for experimental analysis of the diverse human proteome.

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