共查询到20条相似文献,搜索用时 93 毫秒
1.
Elucidation of the genetic diversity and relatedness of the subpopulations of India may provide a unique resource for future analysis of genetic association of several critical community-specific complex diseases. We performed a comprehensive exploration of single nucleotide polymorphisms (SNPs) within the gene DNA ligase 1 (LIG1) among a multiethnic panel of Indian subpopulations representative of the ethnic, linguistic and geographical diversity of India using a two-stage design involving DNA resequencing-based SNP discovery followed by SNP validation using sequenom-based genotyping. Thirty SNPs were identified in LIG1 gene using DNA resequencing including three promoter SNPs and one coding SNP. Following SNP validation, the SNPs rs20580/C19008A and rs3730862/C8804T were found to have the most widespread prevalence with noticeable variations in minor allele frequencies both between the Indian subpopulation groups and also from those reported on other major world populations. Subsequently, SNPs found in Indian subpopulations were analysed using bioinformatics-based approaches and compared with SNP data available on major world populations. Further, we also performed genotype–phenotype association analysis of LIG1 SNPs with publicly available data on LIG1 mRNA expression in HapMap samples. Results showed polymorphisms in LIG1 affect its expression and may therefore change its function. Our results stress upon the uniqueness of the Indian population with respect to the worldwide scenario and suggest that any epidemiological study undertaken on the global population should take this distinctiveness in consideration and avoid making generalized conclusions. 相似文献
2.
Coutinho AM Sousa I Martins M Correia C Morgadinho T Bento C Marques C Ataíde A Miguel TS Moore JH Oliveira G Vicente AM 《Human genetics》2007,121(2):243-256
Autism is a neurodevelopmental disorder of unclear etiology. The consistent finding of platelet hyperserotonemia in a proportion
of patients and its heritability within affected families suggest that genes involved in the serotonin system play a role
in this disorder. The role in autism etiology of seven candidate genes in the serotonin metabolic and neurotransmission pathways
and mapping to autism linkage regions (SLC6A4, HTR1A, HTR1D, HTR2A, HTR5A, TPH1 and ITGB3) was analyzed in a sample of 186 nuclear families. The impact of interactions among these genes in autism was assessed using
the multifactor-dimensionality reduction (MDR) method in 186 patients and 181 controls. We further evaluated whether the effect
of specific gene variants or gene interactions associated with autism etiology might be mediated by their influence on serotonin
levels, using the quantitative transmission disequilibrium test (QTDT) and the restricted partition method (RPM), in a sample
of 109 autistic children. We report a significant main effect of the HTR5A gene in autism (P = 0.0088), and a significant three-locus model comprising a synergistic interaction between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010). In addition to the previously reported contribution of SLC6A4, we found significant associations of ITGB3 haplotypes with serotonin level distribution (P = 0.0163). The most significant models contributing to serotonin distribution were found for interactions between TPH1 rs4537731 and SLC6A4 haplotypes (P = 0.002) and between HTR1D rs6300 and SLC6A4 haplotypes (P = 0.013). In addition to the significant independent effects, evidence for interaction between SLC6A4 and ITGB3 markers was also found. The overall results implicate SLC6A4 and ITGB3 gene interactions in autism etiology and in serotonin level determination, providing evidence for a common underlying genetic
mechanism and a molecular explanation for the association of platelet hyperserotonemia with autism.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
3.
Rubinstein-Taybi syndrome (RSTS), a developmental disorder comprising abnormalities that include mental retardation, an unusual
facial appearance, broad thumbs and big toes is frequently associated with molecular lesions in the CREB-binding protein gene,
CREBBP. The objective of the present study was to identify and analyse CREBBP mutations in Indian RSTS patients on which there are no data. Direct sequencing of CREBBP performed in 13 RSTS patients identified the three zinc fingers (CH1, CH2, CH3) and HAT domain as mutational hotspots in
which ten novel pathogenic mutations were localized. Functional analysis revealed that three of these mutations affecting
amino acids Glu1459, Leu1668 and Glu1724 were critical for histone acetyltransferase activity. Twenty-eight novel CREBBP single-nucleotide polymorphisms (SNPs) were also identified in the Indian population. Linkage disequilibrium studies revealed
associations between (i) SNP (rs129974/c.3836-206G>C) and mutation (p.Asp1340Ala); (ii) (rs130002) with mutation (p.Asn435Lys) and (iii) SNPs rs129974, rs130002 and SNP (c.3836-206G>C) signifying a disease affection status. In conclusion, the present study reports the highest detection rate of CREBBP mutations (76.9%) in RSTS patients to date, of which ten are predicted to be pathogenic and three critical for histone acetyltransferase
activity. Moreover, identification of the association of CREBBP polymorphisms with disease susceptibility could be an important risk factor for the pathogenesis of RSTS. 相似文献
4.
5.
Jerzy K. Kulski Atsuko Shigenari Takashi Shiina Kazuyoshi Hosomichi Makoto Yawata Hidetoshi Inoko 《Immunogenetics》2009,61(4):257-270
The study of the association of the Human Leukocyte Antigen (HLA) alleles and polymorphic retrotransposons such as Alu, HERV, and LTR at various loci within the Major Histocompatibility Complex allows for a better identification and stratification of disease associations and the origins of HLA haplotypes in different populations. This paper provides sequence and association data on two structurally polymorphic MER9-LTR retrotransposons that are located 54 kb apart and in close proximity to the multiallelic HLA-A gene involved in the regulation of the human immune system. Direct DNA sequencing and analysis of the PCR products identified DNA nucleotide variations between the MER9-LTR sequences at the two loci and their associations with HLA-A alleles as potential haplotype and evolutionary markers. All MER9-LTR sequences were haplotypic when associated with common HLA-A alleles. The number of SNP loci was 2.5 times greater for the solo LTR at the AK locus, which is located closer to the HLA-A gene than the solo or 3′ LTR at the HG locus. Our study shows that the nucleotide variations of the MER9-LTR DNA sequences are additional informative markers in fine mapping HLA-A genomic haplotypes for future population, evolutionary, and disease studies. 相似文献
6.
Yiqian Liang Rui Zhang Shuo Zhang Guofa Ji Puyu Shi Tian Yang Feng Liu Jing Feng Chunqi Li Dangshe Guo Mingwei Chen 《Molecular neurobiology》2017,54(8):5988-5995
The development of ischemic stroke is associated with advanced age. Telomere length, as a marker of biological aging, has been reported to influence the risk of several age-related diseases, including ischemic stroke. Recent studies have identified the genetic variant within ACYP2 and TSPYL6 associated with shorter telomere length. The objective of this study is to investigate the putative association of ischemic stroke with common polymorphisms in ACYP2 and TSPYL6 genes in a Chinese Han population. We found that the risk alleles of six single nucleotide polymorphisms (SNPs), including rs11125529, rs12615793, rs843711, rs11896604, and rs843706 within both ACYP2 and TSPYL6, and rs17045754 in ACYP2 gene, were related with increased risk of ischemic stroke according to both allelic and genotype association analyses. The significant correlations between ACYP2 and TSPYL6 SNPs and ischemic stroke risk were also observed in dominant, recessive, and additive models, respectively. Two blocks in high linkage disequilibrium were identified in this study, and two haplotypes were associated with higher ischemic stroke susceptibility. In conclusion, the genetic polymorphisms of ACYP2 and TSPYL6 are associated with increased risk of developing ischemic stroke. Further studies with larger sample sizes are required to validate our findings. 相似文献
7.
A. G. Nikitin E. Y. Lavrikova Y. A. Seregin L. I. Zilberman N. M. Tzitlidze T. L. Kuraeva V. A. Peterkova I. I. Dedov V. V. Nosikov 《Molecular Biology》2010,44(2):228-232
To study the association with diabetes mellitus type 1, we analyzed the distribution of allele and genotype frequencies of
polymorphic marker rs2292239 of ERBB3 gene, encoding epidermal growth factor receptor type 3 and polymorphic marker rs3184504 of SH2B3 gene, encoding adaptor protein LNK. The study included groups of T1DM patients and unrelated controls of Russian origin.
Genotyping was performed using RFLP and real-time amplification methods. No statistically significant association with type
1 diabetes was found for the polymorphic marker rs2292239 of ERBB3, while the analysis of the distribution of allele and genotype frequencies of the polymorphic marker rs3184504 of SH2B3 gene revealed the association with T1DM in the Russian population. 相似文献
8.
E. Yu. Lavrikova A. G. Nikitin Yu. A. Seregin L. I. Zilberman N. M. Tsitlidze T. L. Kuraeva V. A. Peterkova I. I. Dedov V. V. Nosikov 《Molecular Biology》2009,43(6):968-971
PTPN22 encodes a lymphoid protein tyrosine phosphatase LYP. Association of the PTPN22 polymorphism C1858T with type 1 diabetes mellitus was investigated using the transmission disequilibrium test (TDT) and a comparative analysis
of the allele and genotype frequency distributions. The study involved two groups of families from Russian populations of
Moscow and Samara with concordantly (27 families) and discordantly (62 families) affected sibs, as well as groups of type
1 diabetes patients and healthy individuals. The association of the PTPN22 polymorphism with type 1 diabetes was not significant by TDT analysis, but was significant by comparison of the allele and
genotype frequency distributions. Thus, a case-control analysis detected an association of the PTPN22 polymorphism C1858T with type 1 diabetes mellitus in Russians. 相似文献
9.
10.
11.
A. V. Barkhash V. N. Babenko M. I. Voevoda A. G. Romaschenko 《Russian Journal of Genetics》2016,52(6):608-614
The DC-SIGN (dendritic cell-specific intercellular adhesion molecule (ICAM)-3-grabbing non-integrin) and TLR3 (toll-like receptor 3) proteins are key effectors of the innate immunity and particularly play an important role in the organism’s antiviral defense as pattern-recognition receptors. Previously, we demonstrated that certain genotypes and alleles of single nucleotide polymorphisms (SNPs) rs2287886 (G/A) in the promoter region of the CD209 gene (encoding DC-SIGN) and rs3775291 (G/A, Leu412Phe) in the exon 4 of the TLR3 gene are associated with human predisposition to tick-borne encephalitis in the Russian population. In the present work, the distribution of genotype and allele frequencies for these SNPs was studied in seven populations of North Eurasia, including Caucasians (Russians and Germans (from Altai region)), Central Asian Mongoloids (Altaians, Khakass, Tuvinians, and Shorians), and Arctic Mongoloids (Chukchi). It was found that the CD209 gene rs2287886 SNP A/A genotype and A allele, as well as the TLR3 gene rs3775291 SNP G/G genotype and G allele (the frequencies of which in our previous studies were increased in tick-borne encephalitis patients as compared with the population control (Russian citizens of Novosibirsk)), are preserved with a high frequency in Central Asian Mongoloids (who for a long time regularly came in contact with tick-borne encephalitis virus in places of their habitation). We suggested that predisposition to tick-borne encephalitis in Central Asian Mongoloid populations can be predetermined by a different set of genes and their polymorphisms than in the Russian population. 相似文献
12.
Recent studies have identified common variants in or near GC, CYP2R1 and NADSYN1/DHCR7 to be associated with 25-hydroxyvitamin D [25(OH)D] levels in European populations. We aimed to examine whether these variants
also influence 25(OH)D levels in Chinese. Seven common variants were successfully genotyped and tested for associations with
plasma 25(OH)D levels in a population-based cohort of 3,210 Chinese Hans from Beijing and Shanghai. Six common variants at
GC (rs4588, rs7041, rs2282679 and rs1155563) and NADSYN1/DHCR7 (rs3829251 and rs1790349) loci were all significantly associated with lower plasma 25(OH)D levels (−0.036 ≤ β ≤ −0.076 per risk-allele, P ≤ 5.7 × 10−5), while CYP2R1-rs2060793 showed a trend toward association with 25(OH)D levels in the Shanghai subpopulation (P = 0.08), but not in the Beijing subpopulation (P = 0.82). Haplotype-based association analyses of the four GC variants showed that only the haplotype that contained all risk-alleles (TACC) was significantly associated with lower plasma
25(OH)D levels (β = −0.085, P = 2.3 × 10−9), while the haplotype containing the risk-alleles of rs4588 and rs2282679 (TATC) was marginally associated with lower 25(OH)D
levels (β = −0.054, P = 0.0562) when compared with GCTA haplotype carrying the four protective alleles. Most notably, conditional analyses showed
that only GC-rs4588 and GC-rs2282679 (r
2 = 0.97) remained significantly associated with 25(OH)D concentrations (P ≤ 1.9 × 10−5) after adjusting for the other two SNPs in GC. In conclusion, GC and NADSYN1/DHCR7 loci individually and collectively contribute to variation in plasma vitamin D levels in Chinese Hans. 相似文献
13.
Psoriasis (PS; MIM#177900) is a chronic inflammatory immune-mediated skin disorder. Although the disease is believed to be
caused by a combination of genetic, immunologic and environmental factors, its complete etiology has not been fully understood.
Here, we focused on the BSG (MIM#109480), a member of the immunoglobulin superfamily expressed ubiquitously in circulating immune cell populations. We
observed that the expression level of BSG in PBMCs was elevated in psoriasis patients. To understand the underlying mechanism
for this change, we genotyped the rs8259 T>A SNP located in the 3′UTR of the BSG gene from 668 psoriasis patients and 1,143 healthy controls. The rs8259 T allele was associated with significantly decreased psoriasis susceptibility (OR = 0.758, 95% CI 0.638–0.901, p = 0.002). Interestingly, the rs8259 polymorphism was located in a seed region for miR-492 binding. The miR-492 was able to bind to the BSG 3′UTR sequence bearing the rs8259 T allele as assayed by luciferase reporter gene assay. The substitution of T with A abolished miR-492 binding. BSG protein
expression in PBMCs from patients carrying the rs8259 AA genotype was significantly higher than in those from patients carrying the rs8259 TT genotype. Our study suggests that miR-492 may physiologically suppress BSG expression and the BSG rs8259 polymorphism is associated with decreased psoriasis susceptibility through affecting miR-492 binding. 相似文献
14.
15.
The mistyping of the angiotensin I-converting enzyme insertion/deletion (ACE I/D) has been well documented, and new methods have been suggested here to improve the genotyping efficiency. Buccal cell
samples were collected from 157 young Caucasians, and genotyped using previously known and newly developed PCR amplification
genotyping techniques, as well as PCR-RFLP tests for three single nucleotide polymorphisms (rs4327, rs4341 and rs4343). Inconsistent
genotyping results were found when using only the PCR amplification genotyping techniques across repeated attempts (8% to
45%), however, individual SNP genotyping was highly consistent (100%). Two SNPs (rs4341 and rs4343) were in complete LD and
SNP rs4327 was in high LD with the ACE I/D. The ACE I/D was in HW equilibrium in the portion of the population with consistent genotyping results, whereas the three SNPs were
not in HW equilibrium. The mistyping of ACE I/D by only PCR amplification can be improved using alternative methods. 相似文献
16.
Burt C Nicholson P 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2011,123(8):1387-1400
Introgressions into wheat from related species have been widely used as a source of agronomically beneficial traits. One such
example is the introduction of the potent eyespot resistance gene Pch1 from the wild relative Aegilops ventricosa onto chromosome 7DL of wheat. In common with genes carried on many other such introgressions, the use of Pch1 in commercial wheat varieties has been hindered by linkage drag with yield-limiting traits. Attempts to break this linkage
have been frustrated by a lack of co-dominant PCR markers suitable for identifying heterozygotes in F2 populations. We developed conserved orthologous sequence (COS) markers, utilising the Brachypodium distachyon (Brachypodium) genome sequence, to provide co-dominant markers in the Pch1 region. These were supplemented with previously developed sequence-tagged site (STS) markers and simple sequence repeat (SSR)
markers. Markers were applied to a panel of varieties and to a BC6 F2 population, segregating between wheat and Ae. ventricosa over the distal portion of 7DL, to identify recombinants in the region of Pch1. By exploiting co-linearity between wheat chromosome 7D, Brachypodium chromosome 1, rice chromosome 6 and sorghum chromosome
10, Pch1 was located to an interval between the flanking markers Xwg7S and Xcos7-9. Furthermore candidate gene regions were identified in Brachypodium (364 Kb), rice (178 Kb) and sorghum (315 Kb) as a prelude
to the map-based cloning of the gene. In addition, using homoeologue transferable markers, we obtained evidence that the eyespot
resistances Pch1 and Pch2 on chromosomes 7D and 7A, respectively, are potentially homoeoloci. It is anticipated that the COS marker methodology could
be used for the identification of recombinants in other introgressions into wheat from wild relatives. This would assist the
mapping of genes of interest and the breaking of deleterious linkages to enable greater use of these introgressions in commercial
varieties. 相似文献
17.
David N. Kuhn Antonio Figueira Uilson Lopes Juan Carlos Motamayor Alan W. Meerow Kathleen Cariaga Barbie Freeman Donald S. LivingstoneIII Raymond J. Schnell 《Tree Genetics & Genomes》2010,6(5):783-792
The seeds of Theobroma cacao (cacao) are the source of cocoa, the raw material for the multi-billion dollar chocolate industry. Cacao’s two most important
traits are its unique seed storage triglyceride (cocoa butter) and the flavor of its fermented beans (chocolate). The genome
of T. cacao is being sequenced, and to expand the utility of the genome sequence to the improvement of cacao, we are evaluating Theobroma grandiflorum, the closest economically important species of Theobroma for its potential use in a comparative genomic study. T. grandiflorum differs from cacao in important agronomic traits such as flavor of the fermented beans, disease resistance to witches’ broom
and abscission of mature fruits. By comparing genomic sequences and analyzing viable inter-specific hybrids, we hope to identify
the key genes that regulate cacao’s most important traits. We have investigated the utility in T. grandiflorum of three types of markers (microsatellite markers, single-strand conformational polymorphism markers and single nucleotide
polymorphism (SNP) markers) developed in cacao. Through sequencing of amplicons of 12 diverse individuals of both cacao and
T. grandiflorum, we have identified new intra- and inter-specific SNPs. Two markers which had no overlap of alleles between the species were
used to genotype putative inter-specific hybrid seedlings. Sequence conservation was significant and species-specific differences
numerous enough to suggest that comparative genomics of T. grandiflorum and T. cacao will be useful in elucidating the genetic differences that lead to a variety of important agronomic trait differences. 相似文献
18.
Gu H Qiu W Wan Y Ding G Tang W Liu C Shi Y Chen Y Chen S 《Molecular biology reports》2012,39(5):5977-5984
Growing evidence suggests that the checkpoint kinase 2 (CHEK2) signaling pathway occupies a central position in the signaling
networks of DNA-damage signaling. Many functional and molecular epidemiological studies have evaluated the association between
genetic variants of CHEK2 and various cancers. To evaluate the relationship between CHEK2 functional genetic variants and esophageal cancer risk and the risk of lymph node metastasis among a Chinese population.
We genotyped CHEK2 rs738722, rs2236141 and rs2236142 single nucleotide polymorphisms (SNPs) using the matrix assisted laser desorption/ionization
time-of-flight mass spectrometry assay in a case–controlled study, including 380 esophageal cancer cases and 380 healthy controls
in a Chinese population. We found that none of the three polymorphisms achieved significant difference in their distributions
between esophageal cancer cases and controls. Multiple logistic regression analyses revealed that esophageal cancer risk was
not associated significantly with the variant genotypes of the three CHEK2 polymorphisms as compared with their wild-type genotypes. However, we found that functional variant rs738722 and rs2236142
in CHEK2 might contribute to susceptibility to lymph node metastasis. Our data did not support a significant association between CHEK2 SNPs and the risk of esophageal cancer. Functional variant CHEK2 rs738722 and rs2236142 might contribute to lymph node metastasis susceptibility. The CT allele of SNP rs738722 and the GC
allele of SNP rs2236142 might be a protective factor of the risk for lymph node metastasis of esophageal cancer. 相似文献
19.
Cortés AJ Chavarro MC Blair MW 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2011,123(5):827-845
Single nucleotide polymorphism (SNP) markers have become a genetic technology of choice because of their automation and high
precision of allele calls. In this study, our goal was to develop 94 SNPs and test them across well-chosen common bean (Phaseolus vulgaris L.) germplasm. We validated and accessed SNP diversity at 84 gene-based and 10 non-genic loci using KASPar technology in
a panel of 70 genotypes that have been used as parents of mapping populations and have been previously evaluated for SSRs.
SNPs exhibited high levels of genetic diversity, an excess of middle frequency polymorphism, and a within-genepool mismatch
distribution as expected for populations affected by sudden demographic expansions after domestication bottlenecks. This set
of markers was useful for distinguishing Andean and Mesoamerican genotypes but less useful for distinguishing within each
gene pool. In summary, slightly greater polymorphism and race structure was found within the Andean gene pool than within
the Mesoamerican gene pool but polymorphism rate between genotypes was consistent with genepool and race identity. Our survey
results represent a baseline for the choice of SNP markers for future applications because gene-associated SNPs could themselves
be causative SNPs for traits. Finally, we discuss that the ideal genetic marker combination with which to carry out diversity,
mapping and association studies in common bean should consider a mix of both SNP and SSR markers. 相似文献
20.
Fuli Liu Xiuliang Wang Jianting Yao Wandong Fu Delin Duan 《Journal of applied phycology》2010,22(1):109-111
Expressed sequence tag-derived microsatellite markers (EST-SSR) were generated and characterized in Laminaria japonica using data mining from updated public EST databases and polymorphism testing. Fifty-eight of 578 ESTs (10.0%) containing
various repeat motifs were used to design polymerase chain reaction (PCR) amplification primers. A total of 12 pairs of primer
were generated and used in the PCR amplification. Alleles per locus ranged from two to ten (average of 5.7). The observed
heterozygosities and expected heterozygosities were from 0.045 to 0.543 and from 0.056 to 0.814, respectively. All loci were
in Hardy–Weinberg equilibrium and no linkage disequilibrium was detected. These robust, informative, and potentially transferable
polymorphic markers appear suitable for population, genetic, parentage, and mapping studies of L. japonica. 相似文献