Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson’s disease.

Development of organelle single nucleotide polymorphism (SNP) markers and their application for the identification of cytoplasmic inheritance patterns in Pyropia yezoensis (Bangiales,Rhodophyta)

The genus Pyropia contains several important cultivated species.Genetic research in nori species has mainly focused on the cell nucleus,with few studies on organelles(chloroplast and mitochondria).Due to the high copy numbers of organelles in cells,which influence the development and traits of algae,it is necessary to study their genetic mechanism.In this study,the marine red alga Pyropia yezoensis,an important economic macroalga,was selected as the study object.To investigate organelle(chloroplast and mitochondria)inheritance in P.yezoensis,the wild type RZ(maternal strain)was crossed with the red mutant HT(paternal strain)and 30 color-sectors from 11 F1 gametophytic blades were examined.The complete chloroplast and mitochondrial genomes of the red mutant(HT)were assembled for the first time.One reliable and stable single nucleotide polymorphism(SNP)loci filtrated by bioinformatics analysis was used as a molecular marker for chloroplast and mitochondrial DNA,respectively,in subsequent experiments.PCR amplification and sequence analysis showed that the haplotypes of color-sectors detected were consistent with those of the maternal parent,confirming that both chloroplast and mitochondrial genomes were inherited maternally in P.yezoensis.The inheritance pattern of organelles in P.yezoensis can be used to guide the hybridization and breeding of nori.Additionally,the organelle SNP markers developed in this study can be applied in subsequent genetic research.

Gene-gene,gene-environment,gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus(T2DM).The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury,oxidative stress and beta cell apoptosis in T2 DM.Among the recognized markers are interleukin(IL)-6,IL-1,IL-10,IL-18,tissue necrosis factor-alpha(TNF-α),C-reactive protein,resistin,adiponectin,tissue plasminogen activator,fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance.Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatory cytokines have been reported as a risk for T2 DM.Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups.The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions.This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6,TNF-α,resistin and adiponectin in pathogenesis of T2 DM.

Association between low molecular polypeptide 7 single nucleotide polymorphism and response to therapy in hepatitis C virus infection

AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease Bsm I and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of thissingle nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy. RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient's sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P < 0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of patients carrying LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that genotype CC was strongly associated with response to interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters recorded in SVR and NR patients included higher values of mean age (P = 0.004), alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025), viral load (P = 0.025), higher fibrosis and histological activity index indices among NR vs SVR patients. Also, the multivariate statistical analysis of the different factors of fibro-sis score, liver activity grade, genotypes and alleles of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study showed that HCV patients with A allele had a very highly significant association with the NRs, high fibrosis and higher liver activity, while the C allele had a very highly significant association with the responders, low fibrosis and lower liver activity (95%CI: 3.5800-13.2519, P = 0.0001).CONCLUSION: LMP-7 SNP is a candidate gene that should be considered when designing a mathematical model for predicting response to therapy and disease progression in HCV patients.

Correlation between single nucleotide polymorphism of rs3811047 in IL-1 F7 gene and rheumatoid arthritis susceptibility among Han population in central plains of China

Objective:To discuss the association between single nucleotide polymorphism(SNP) of rs3811047 in IL-1 F7 gene and rheumatoid arthritis(RA) susceptibility among the Han population in central plains of China.Methods:A total of 276 RA patients admitted to our hospital from December 2009 to December 2011 together with 276 healthy physical examinees in the same period were chosen as the subjects.The typing for rs3811047 SNP in IL-1 F7 gene was carried out by using ligase detection reaction and polymerase chain reaction technique.And the frequency of each allele and genotypes distribution was calculated so as to evaluate the association between genotype distribution and RA susceptibility.Results:The frequency of A allele of rs3811047 in IL-1 F7 gene in RA group and control group was 16.27%and 17.68%,respectively,and that of G allele in two groups was 83.73%and 82.32%,respectively.The difference between two groups wasn’t statistical significant(P 】0.05).The frequency of genotype AA,AG and GG in RA group was 2.19%,27.84%and 69.97%,respectively,while that in control group was 2.94%,29.78%and 67.28%, respectively.The difference of distribution of three genotypes was not statistically significant (P 】0.05).RA patients with A allele were better than those without A allele in joint swelling index, rest pain,HAQ scoring and blood sedimentation.There was significant difference between two groups in above indexes(P【0.05/P【0.01).Conclusions:No significant correlation between RA susceptibility among the Han population in central plains of China and rs3811047 SNP inIL-1 F7 gene is observed.However,A allele of rs3811047 has certain influence on the condition of RA patients.

Isolation,expression and single nucleotide polymorphisms(SNPs) analysis of LACCASE gene(LkLAC8) from Japanese larch(Larix kaempferi)

Nucleotide diversity(π) and linkage disequilibrium(LD) analysis based on SNP marker could provide a sound basis for choosing an association analysis method.Japanese larch(Larix kaempferi) is an important timber coniferous tree species for pulping and papermaking,but its high lignin content has significantly restricted it application potential.In this study,the LACCASE gene,that plays an important regulatory role for lignin biosynthesis,was selected as research target.The full-length c DNA and genomic sequences of the encoding Lk LAC8 gene were isolated from the LACCASE expressed sequence tags of the Japanese larch transcriptome database using the rapid amplification of c DNA ends-polymerase chain reaction(RACE-PCR).The c DNA was determined to be 1940 bp,with an open reading frame(ORF,1734 bp) that encoded a protein of 577 AA.This protein contains four highly specific Cu^(2+) binding sites and 11 glycosylation sites,thus belonging to the LACCASE family.The deduced protein sequence shared an 89% identity with the Pta LAC from Pinus taeda.A real-time PCR analysis showed that the Lk LAC8 transcript was expressed predominantly in mature xylem,with moderate levels in the immature xylem,cambium and mature leaves,the lowest in the roots.Lastly,the genomic sequences of Lk LAC8 in 40 individuals from six naturally distributed populations of Japanese larch were amplified,and a total of 201 SNPs(103 and 98 mutation types of transition and transversion,respectively) were detected;the frequency of the SNPs was 1/19 bp.Nucleotide diversity among the six populations ranged from 0.0034 to 0.0053,which suggested that there were no significant differences among the populations.The LD analysis showed that the LD level decayed rapidly within the increasing length of the Lk LAC8 gene.These results implied that LD mapping and association analysis based on candidate gene may be feasible for the marker-assisted breeding of new germplasms with low lignin in Japanese larch.

A single nucleotide polymorphism in the IL1RL1 gene is associated with Behcet's disease in a Chinese Han population

AIM:To explore the association of single nucleotide polymorphisms(SNPs)in the IL33/IL1RL1 gene region with the susceptibility to Behcet’s disease(BD)in a Chinese Han population.METHODS:A total of eight SNPs in the candidate gene region(rs11792633,rs7025417,rs10975519 and rs1048274 in IL33;rs2310220,rs12712142,rs13424006 and rs3821204 in IL1RL1)were genotyped in783 BD patients and 701 healthy controls by the Sequenom Mass Array i PLEX platform.RESULTS:A statistically significant association was observed between IL1RL1 rs12712142 and BD patients.The frequency of IL1RL1 rs12712142 variant allele A was significantly lower in BD patients than that in controls(OR=0.8,95%CI:0.69-0.94,Pc=0.039);the genotype distribution(Pc=0.043)and additive and dominant genetic model analyses(OR=0.8,95%CI:0.69-0.94,Pc=0.040 and OR=0.72,95%CI:0.58-0.88,Pc=0.011)also indicated a strong association between rs12712142 and BD patients.CONCLUSION:This is the first study to reveal the association between IL1RL1 rs12712142 variant allele A and the decreased risk of BD in the Chinese Han population,indicating a protective role of IL1RL1 in the pathogenesis of BD.

Identifying changes in punitive transcriptional factor binding sites from regulatory single nucleotide polymorphisms that are significantly associated with disease or sickness

AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies have provided us with nearly 6500 disease or trait-predisposing SNPs where 93% are located within non-coding regions such as gene regulatory or intergenic areas of the genome. In the regulatory region of a gene, a SNP can change the DNA sequence of a transcriptional factor(TF) motif and in turn may affect the process of gene regulation. SNP changes that affect gene expression and impact gene regulatory sequences such as promoters, enhancers, and silencers are known as rS NPs. Computational tools can be used to identify unique punitive TFBS created by rS NPs that are associated with disease or sickness. Computational analysis was used to identify punitive TFBS generated by the alleles of these rS NPs.RESULTS r SNPs within nine genes that have been significantly associated with disease or sickness were used to illustrate the tremendous diversity of punitive unique TFBS that can be generated by their alleles. The genes studied are the adrenergic, beta, receptor kinase 1, the v-akt murine thymoma viral oncogene homolog 3, the activating transcription factor 3, the type 2 demodkinase gene, the endothetal Per-Arnt-Sim domain protein 1, the lysosomal acid lipase A, the signal Transducer and Activator of Transcription 4, the thromboxane A2 receptor and the vascular endothelial growth factor A. From this sampling of SNPs among the nine genes, there are 73 potential unique TFBS generated by the common alleles comparedto 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of regulating these genes.CONCLUSION From the diversity of unique punitive binding sites for TFs, it was found that some TFs play a role in the disease or sickness being studied.

Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer

Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer(CRC) have been described.Case presentation: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a micro RNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.Conclusions: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.

Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease

AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients with inflammatory bowel disease,Crohn's disease(CD)or ulcerative colitis were investigated using both a casecontrol study approach(one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls)and a family-based study(463 non-Swedish European inflammatory bowel disease-families).A nonsynonymous coding single nucleotide polymorphism in MORC4,located on the same linkage block as CLDN2,was investigated for association,as were two novel CLDN2 single nucleotide polymorphism markers,identified by resequencing.RESULTS:A single nucleotide polymorphism marker(rs12014762)located in the genetic region of CLDN2 was significantly associated to CD(case-control allelic OR = 1.98,95%CI:1.17-3.35,P = 0.007).MORC4 was present on the same linkage block as this CD marker.Using the case-control approach,a significant association(case control allelic OR = 1.61,95%CI:1.08-2.41,P = 0.018)was found between CD and a nonsynonymous coding single nucleotide polymorphism(rs6622126)in MORC4.The association between the CLDN2 marker and CD was not replicated in the familybased study.Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION:These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

Association of eleven single nucleotide polymorphisms with refractive disorders from Eskisehir,Turkey

AIM:To investigate relationship between refractive errors and eleven single nucleotide polymorphisms(SNPs)in HGF,GC,MFN1,GNB4,and VDR genes in Turkish population.METHODS:A group of 212 participants with myopia(n=91),hyperopia(n=45),and emmetropia(n=76)were investigated in this study.SNPs in HGF,GC,MFN1,GNB4 and VDR genes were studied by Snap Shot technique.RESULTS:The patients in this study consists of 47 female/44 male(age:23.47±4.30)patients with myopia,20 female/25 male(age:31.20±8.02)with hyperopia and 33 female/43 male(age:25.22±6.60)with emmetropia.The genotype distribution of the rs7618348 polymorphism,which was the only statistically significant one between myopia and emmetropia group.The genotype distribution of the rs3819545,rs3735520,rs7041,and rs2239182 polymorphisms,which were statistically significant between hyperopia and emmetropia groups.CONCLUSION:The importance of genetic predisposition to refractive errors with respect to etiology of the disease is revealed.It is known that polymorphism studies may differ because of genetic diversity among populations so larger cohort studies are required in different populations to enlighten the etiology of the refractive errors.

Assessment of single nucleotide polymorphisms associated with steroid-induced ocular hypertension

AIM:To access the association of forty-eight single nucleotide polymorphisms(SNPs)identified from Caucasian population with steroid-induced ocular hypertension(OHT)in India population.METHODS:Fifty-four triamcinolone-acetonide(TA)and for ty-seven dexamethasone(Dex)administered subjects were enrolled in the study after a written consent.Intraocular pressure(IOP)values were recorded for a period of 6-month post steroid injections and patients were grouped as steroid-responders(SR:IOP≥21 mm Hg)and non-responders(NR:IOP≤20 mm Hg).Genomic DNA was isolated from peripheral venous blood.Forty-eight SNPs identified in TA treated Caucasian patients by genome wide association study(GWAS)were genotyped using iPLEXTM MassA RRAY among TA as well as Dex administered Indian patients.Genotyping data of 48 general subjects from a previous study were considered as reference controls for statistical analysis.Genotypic frequencies were calculated and P-value,Chi-square and odds ratio at 95%confidenceinterval of group A(steroid treated vs controls),group B(SR vs NR),group C(phenotype correlation:influence of time,severity and gender on IOP rise),were calculated.P<0.05 was considered to be statistically significant.RESULTS:OHT was observed in 50%of TA and 26%of Dex administered patients,respectively.IOP rise was mostly severe(>30 mm Hg)and immediate(<1 wk)among TA-SR patients while it was noticed to be mild(<30 mm Hg)and between 1-2 mo among Dex-SR patients.Logistic regression for risk factor correlation with OHT remained non-significant,hence these factors were not considered as confounding parameters for further analysis.rs133,rs34016742,rs274554,rs10936746,rs274547,rs804854,rs7751500,rs359498,and rs7547448 SNPs significantly varied even after Bonferroni corrections(P<0.0025;group A).rs1879370(TA)and rs6559662(Dex)were significantly(P<0.05)associated with OHT(group B).rs133(severe IOP rise),rs11047639 and rs1879370(male gender),and rs11171569(immediate IOP rise)significantly(P<0.05)influenced the phenotype correlation only among TAOHT patients.However,the significance of these SNPs in group B and phenotype analysis(group C)was lost upon Bonferroni corrections(P<0.0025).CONCLUSION:Prevalence of OHT in study population is observed to be similar to other studies both in TA and Dex treated patients.We can correlate rs34016742 involved in diabetes signaling pathway to the occurrence of ocular edematous and inflammatory conditions.Except rs133 that is involved in neuro-degeneration and myopia occurrence,none of the other SNPs identified in Caucasian population possess any correlation with OHT incidence in TA and Dex administered Indian subjects.

Replicated association of the single nucleotide polymorphism in PNLIP with marbling in Niigata population of Japanese Black beef cattle

Marbling is regarded as an economically important trait of beef cattle inJapan, and measured as a beef marbling score (BMS). Our previous study reported an association between a single nucleotide polymorphism (SNP), rs4164 8172, in the pancreatic lipase (PNLIP) gene and the BMS level, using the Japanese Black beef cattle population of Oita prefecture. Further, we showed that the T allele at the rs41648172 SNP is associated with a high level of the BMS. Thus, we suggested that the rs41648172 SNP seems to be a candidate marker for marker-assisted selection. Our present study was designed to investigate whether this association could be replicated in other independent Japanese Black cattle population and analyze the effect of the SNP genotypes on the carcass traits other than the BMS. We detected the marginally significant effect of the genotypes of the rs41648172 SNP on the BMS level by using the Japanese Black beef cattle population of Niigata prefecture (P = 0.0919), and obtained the result of the T allele associated with an increase in the BMS level, consistent with our previous data. In addition, we showed no significant association of the SNP with the subcutaneous fat thickness, carcass weight, rib eye area, rib thickness and yield estimate in the Japanese Black beef cattle population ofNiigataprefecture. Thus, we concluded that the rs41648172 SNP was useful for effective marker-assisted selection to increase the BMS level in Japanese Black beef cattle, based on the replicated association of the rs41648172 SNP with the BMS level in the other independent Japanese Black beef cattle population and no effect of the SNP genotypes on the carcass traits other than BMS.

Cancer Specific Non-Synonymous Single Nucleotide Polymorphism Prediction in the Context of Haplotype and Protein Interacting Sites

In this work, we study predicting the effect of non-synonymous SNPs on several cancers. We trained classifiers on both sequential and structural features extracted from the affected genes and assessed the predictions made by the trained classifiers using cross validation. Specifically, we investigated how the prediction performance can be improved by connecting SNPs in the context of haplotype and interacting sites of proteins encoded by affected genes. We found that accuracy was consistently enhanced by combining sequential and structural features, with increase ranging from a few percentage points up to more than 20 percentage points. The results for putting SNPs in the context of interacting sites were less consistent. Compared to individual SNPs, these that appear together in haplotype showed stronger correlation with one another and with the phenotype, and therefore led to significant improvement inprediction performance, with ROC score increased from 0.81 to 0.95. Although some similar effect has been expected for connecting SNPs to interacting sites in proteins, the performance actually got worse. This decrease in prediction accuracy may be caused by the small data set being used in the study, as many affected proteins in the study do not have known interacting sites.

Identification of Single Nucleotide Polymorphisms and Analysis of Linkage Disequilibrium in Different Bamboo Species Using the Candidate Gene Approach

Bamboos are one of the most beautiful and useful plants on Earth.The genetic background and population structure of bamboos are well known,which helps accelerate the process of artificial domestication of bamboo.Partial sequences of six genes involved in nitrogen use efficiency in 32 different bamboo species were analyzed for occurrence of single nucleotide polymorphisms(SNPs).The nucleotide diversityθw and total nucleotide polymorphismsπT of the sequenced DNA regions was 0.05137 and 0.03332,respectively.Bothπnonsyn/πsyn and Ka/Ks values were<1.The nucleotide sequences of these six genes were inferred to be relatively conserved,and the haplotype diversity was relatively high.The results of evolutionary neutrality tests showed that the six genes were in line with neutral evolution,and that the NRT2.1 and AMT2.1 gene sequences may have experienced negative selection.An inter-SNP recombination event at the NRT2.1 gene in the all pooled sample,of all 32 bamboo species was the lowest at 0.0645,whereas the AMT gene recombination events were all>0.1.Estimation and analysis of linkage disequilibrium of five genes revealed that with the increase in nucleotide sequence length,the degree of SNP linkage disequilibrium decreased rapidly.We inferred the population genetic structure of 32 bamboo species based on the SNP loci of six genes with frequencies>18%.32 bamboo species were divided into five categories,which indicated that the combined population of all bamboo species had obvious multivariate characteristics and was heterogeneous;red(Group 1)and green(Group 2)were the main groups.

Significant association of a single nucleotide polymorphism in the upstream region of FGFR1OP2/wit3.0 gene with residual ridge resorption of mandible in Saudis

Residual ridge resorption(RRR)is the decrease in the jaw structure that follows tooth extraction.It is a multifactorial disorder,but reports on the associated genetic factors are scarce,particularly amongst the Saudis.This study aimed to investigate the role of single nucleotide polymorphisms(SNPs)in fibroblast growth factor receptor 1 oncogene partner 2(FGFR1OP2)in RRR development in Saudis.The study included 192 individuals(RRR=96;controls=96)attending outpatient clinics at the College of Dentistry,King Saud University.Demographic and clinical data were collected,the digital panoramic dental radiograph was obtained,and mandibular residual ridge height was measured.DNA was extracted from saliva and genotyping was conducted on“Sequenom MassARRAY iPLEX”.Genotype and allele frequencies of three SNPs were calculated and compared.The age at first diagnosis and bone height were compared in the three genotypes of each SNP.The age of the patients,age at first edentulism,and bone height ranged 21-80 years,12-70 years,and 13-34.6 mm,respectively.All three genotypes of the studied SNPs(rs2279351,rs78054962 and rs2306852)were identified.SNP rs2279351 associated significantly with RRR,and the mutant C allele was highly predisposing.No association was observed for the other two SNPs.The genotypes of all SNPs had an influence on age at first edentulism and bone height,but the results were not statistically different.Since FGFR1OP2 plays a role in the process of rapid wound healing in the oral cavity,it may be playing a role in the development of RRR by influencing the rate of resorption of the jawbone.SNP rs2279351 may alter its expression and hence RRR development.This study is limited due to small a sample size,and further large-scale studies are required to confirm this association and to consider rs2279351 as a possible marker of RRR development.

Estimated Genetic Variance Explained by Single Nucleotide Polymorphisms of Different Minor Allele Frequencies for Carcass Traits in Japanese Black Cattle

Japanese Black cattle are a beef breed and well known to excel in carcass quality, but the details of genetic architectures for carcass traits in beef breeds including this breed are still poorly understood. The objective of this study was to estimate the degree of additive genetic variance explained by single nucleotide polymorphism (SNP) marker groups with different levels of minor allele frequency (MAF) for marbling score and carcass weight in Japanese Black cattle. Phenotypic data on 872 fattened steers with the genotype information about 40,000 autosomal SNPs were analyzed using two different statistical models: one considering only SNPs selected based on MAF (model 1) and the other also considering all remaining SNPs as the different term (model 2). All available SNPs were classified into 10 groups based on their MAFs. For both traits, the estimated proportions of additive genetic variance explained by SNPs selected based on their MAFs using model 1 were always higher than the estimated ones using model 2. For carcass weight, relatively high values of the proportion of the additive genetic variance were estimated when using SNPs with MAFs which were in the ranges of 0.20 to 0.25 and 0.25 to 0.30, which may be partly due to the three previously-reported quantitative trait loci candidate regions. The results could have provided some information on the genetic architecture for the carcass traits in Japanese Black cattle, although its validity may be limited, mainly due to the sample size and the use of simpler statistical models in this study.

Advances in Single Nucleotide Polymorphisms of Vitamin D Metabolic Pathway Genes and Respiratory Diseases

Vitamin D is a fat-soluble vitamin.It is an essential vitamin for human body.It has a classical effect on regulating calcium and phosphorus metabolism.Participate in cellular and humoral immune processes by regulating the growth,differentiation and metabolism of immune cells.A large number of studies in recent years have shown that vitamin D deficiency increases the incidence of respiratory diseases.Respiratory diseases mainly include bronchial asthma,chronic obstructive pulmonary disease,tuberculosis,acute upper respiratory tract infection and pneumonia.Vitamin D metabolic pathway genes play a very important regulatory role in the transformation of vitamin D into active vitamin D,including CYP2R1,CYP27B1,CYP24A1,VDBP,VDR five genes.Genetic polymorphism of genes is the molecular basis of individual differences and disease development.Therefore,this paper summarizes the research on single nucleotide polymorphism of vitamin D metabolic pathway gene and respiratory diseases.In order to provide a new idea for future treatment.

Relationship between ERCC1 (C8092A) single nucleotide polymorphism and efficacy/toxicity of platinum based chemotherapy in advanced non-small cell lung cancer patients

To assses the effect of single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A on the clinical outcome and toxicity in advanced stage non-small cell lung cancer patients receiving first line platinum based chemotherapy.MethodsThis article is a review of the current research on single nucleotide polymorphism and its effect on treatment outcome and toxicity of advanced stage lung cancer.Conclusion The observations indicate that more advanced studies and trials on C8092A SNPs are needed so as to assess if it could be used as a potential biomarker in the future.

Null Single Nucleotide Polymorphism in Chemokine Receptor 5 (CCR5) Genes among the Ijaw Ethnic Population of Nigeria

Background: A deletion of 32 bp in the nucleotide sequence of CCR5 gene results in a defective CCR5 which confers protection from HIV infection in the homozygous state, while reducing the rate of disease progression to AIDS and death in the heterozygous state. The status of the CCR5Δ32 gene has not been reported in Nigeria. Aim: This study was aimed at analyzing single nucleotide polymorphism of CCR5 gene among the Ijaws resident in Yenagoa, Nigeria. Methods: 100 subjects (75 HIV negative and 25 HIV positive control) were recruited for this study. The CCR5 genes were amplified by 2 Stage PCR reaction using GeneAmp 9700 PCR system utilizing specific primers that would flank 32 bp deletion, followed by agarose gel electrophoresis, DNA sequencing of 20 subjects was done followed by phylogenetic and polymorphism analysis. Results: The results showed that 75 (100%) of the HIV negative subjects had 189 base pair in their CCR5 gene. Nucleotide of the 20 (100%) of the sequenced samples were conservatively same and no SNP was observed. Conclusion: This study documented no SNPs in CCR5 gene of the study population hence;the study population has no protection from HIV infection.