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Background: The establishment of new methods to detect human genetic variations, such as single nucleotide polymorphisms, is of importance in hereditary disease diagnosis and pharmacogenomics. Several single nucleotide polymorphism genotyping technologies have been presented in recent years. However, techniques which would allow accurate, fast and cheap allelic determination and multiple single nucleotide polymorphism detection in parallel are still in great need. Methods: Here, we present a new genotyping technique based on gap ligase chain reaction and a fluorescent polystyrene microsphere measurement platform. We chose the human polymorphism rs3730386 as our candidate to establish this method. Probes for gap ligase chain reaction were designed to recognize the target alleles sensitively and specifically and to produce templates for amplifying the correspondent target fragments used in the following hybridization. The genotypes were finally determined by a hybridization process based on the Luminex fluorescent polystyrene microspheres measurement platform. Results: This method was successfully applied for the detection of selected single nucleotide polymorphisms with high sensitivity and specificity. The genotypes were validated by DNA sequencing. Conclusions: The new genotyping method benefited from the high sensitivity and specificity of gap ligase chain reaction and the detection platform of Luminex. The method allows multiplex analysis of single nucleotide polymorphism, because 100 types of microspheres are available from Luminex. Clin Chem Lab Med 2008;46:486–9. [ABSTRACT FROM AUTHOR]

Introgression lines (ILs) are useful tools for precise mapping of quantitative trait loci (QTLs) and the evaluation of gene action or interaction in theoretical studies. A set of 159 ILs carrying variant introgressed segments from Chinese common wild rice ( Oryza rufipogon Griff.), collected from Dongxiang county, Jiangxi Province, in the background of Indica cultivar ( Oryza sativa L.), Guichao 2, was developed using 126 polymorphic simple sequence repeats (SSR) loci. The 159 ILs represented 67.5% of the genome of O. rufipogon. All the ILs have the proportions of the recurrent parent ranging from 92.4 to 99.9%, with an average of 97.4%. The average proportion of the donor genome for the BC4F4 population was about 2.2%. The mean numbers of homozygous and heterozygous donor segments were 2 (ranging 0–8) and 1 (ranging 0–7), respectively, and the majority of these segments had sizes less than 10 cM. QTL analysis was conducted based on evaluation of yield-related traits of the 159 ILs at two sites, in Beijing and Hainan. For 6 out of 17 QTLs identified at two sites corresponding to three traits (panicles per plant, grains per panicle and filled grains per plant, respectively), the QTLs derived from O. rufipogon were usually associated with an improvement of the target trait, although the overall phenotypic characters of O. rufipogon were inferior to that of the recurrent parent. Of the 17 QTLs, 5 specific QTLs strongly associated with more than one trait were observed. Further analysis of the high-yielding and low-yielding ILs revealed that the high-yielding ILs contained relatively less introgressed segments than the low-yielding ILs, and that the yield increase or decrease was mainly due to the number of grain. On the other hand, low-yielding ILs contained more negative QTLs or disharmonious interactions between QTLs which masked trait-enchancing QTLs. These ILs will be useful in identifying the traits of yield, tolerance to low temperature and drought stress, and detecting favorable genes of common wild rice. [ABSTRACT FROM AUTHOR]

Purpose: Several researchers have suggested that the rs4779584 (15q13.3) polymorphism is associated with an increased risk of developing colorectal cancer (CRC). However, past results remain inconclusive. We addressed this controversy by performing a meta-analysis of the relationship between rs4779584 of GREM1-SCG5 and colorectal cancer. Methods: We selected 12 case-control studies involving 11,769 cases of CRC and 14,328 healthy controls. The association between the rs4779584 polymorphism and CRC was examined by the overall odds ratio (OR) with a 95% confidence interval (CI). We used different genetic model analyses, sensitivity analyses, and assessments of bias in our meta-analysis. Results: GREM1-SCG5 rs4779584 polymorphisms were associated with CRC in all of the genetic models that were examined in this meta-analysis of 12 case-control studies. Conclusion: GREM1-SCG5 rs4779584 polymorphisms may increase the risk of developing colorectal cancer. [ABSTRACT FROM AUTHOR]

Background and Aims Recent genome-wide association studies have shown associations between variants in loci (4q28.1, 6p21.32, 6p21.1, 6q16.1, 10q22.1 and 10q22.3) and chronic obstructive pulmonary disease (COPD) or smoking behaviors. The objective of this study was to look for associations between 16 single nucleotide polymorphisms (SNP) at these six loci and COPD susceptibility in Hainan region. Methods A case-control cohort was composed of 200 COPD cases and 401 controls that were genotyped and analyzed statistically. Odds ratios (OR) and 95% confidence intervals (CIs) were computed by chi-square (χ2) test and genetic models by unconditional logistic regression. Results After Hardy-Weinberg equilibrium (HWE) P value screening, we excluded the SNP rs12220777 with P < 0.001. By χ2 test only rs9296092 which located on 6p21.32 was provided the strongest evidence of an increasing risk of COPD with an OR of 3.28 (95% CI = 1.03 - 2.32; P = 0.003) between cases and controls. By genetic models analysis, we not only found rs9296092 increased COPD risk, but also found in the over-dominant model the genotype 'C/T' (OR = 0.55; 95% CI = 0.33 - 0.93; P = 0.023) of rs950063 was proved to be associated with decreased COPD risk. Conclusions This study is the first to provide evidence of importance of rs9296092 and rs950063 for risk of COPD in Hainan Province. Further studies are needed to characterize the functional sequences that cause COPD. [ABSTRACT FROM AUTHOR]

Genetic variations in cytochrome P450 2C9 are known to contribute to interindividual and interethnic variability in response to clinical drugs, but little is known about the genetic variation of CYP2C9 in the Uyghur population.We directly sequenced the whole CYP2C9 gene in 96 unrelated, healthy Uyghur from Xinjiang Uygur Autonomous Region of China and screened for genetic variants in the promoter, exons, introns and 3′-UTR.Thirty five previously reported alleles and six genotypes were detected in this study. The allele frequencies of CYP2C9*1, *2, *11, *12, *29 and *33 were 89.58, 7.81, 0.52, 0.52, 1.04 and 0.52%, respectively. We detected one non-synonymous novel variant at position 329 from Arg to Cys and this mutation is predicted to be intolerant by SIFT.Our results provide basic information about CYP2C9 alleles in Uyghur, which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group. [ABSTRACT FROM PUBLISHER]

Little is known about polymorphic distribution of pharmacogenes among ethnicities, including the Deng people. In this study, we recruited 100 unrelated, healthy Deng people and genotyped them with respect to 76 different single-nucleotide polymorphisms by the PharmGKB database. Our results first indicated that the polymorphic distribution of pharmacogenes of the Deng people is most similar to CHD, suggesting that Deng people have a closest genetic relationship with CHD. Our data will enrich the database of pharmacogenomics and provide a theoretical basis for safer drug administration and individualized treatment plans, promoting the development of personalized medicine. [ABSTRACT FROM PUBLISHER]

The complex genomes of many economically important crops present tremendous challenges to understand the genetic control of many quantitative traits with great importance in crop production, adaptation, and evolution. Advances in genomic technology need to be integrated with strategic genetic design and novel perspectives to break new ground. Complementary to individual-gene--targeted research, which remains challenging, a global assessment of the genomic distribution of trait-associated SNPs (TASs) discovered from genome scans of quantitative traits can provide insights into the genetic architecture and contribute to the design of future studies. Here we report the first systematic tabulation of the relative contribution of different genomic regions to quantitative trait variation in maize. We found that TASs were enriched in the nongenic regions, particularly within a 5-kb window upstream of genes, which highlights the importance of polymorphisms regulating gene expression in shaping the natural variation. Consistent with these findings, TASs collectively explained 44%-59% of the total phenotypic variation across maize quantitative traits, and on average, 79% of the explained variation could be attributed to TASs located in genes or within 5 kb upstream of genes, which together comprise only 13% of the genome. Our findings suggest that efficient, cost-effective genome-wide association studies (GWAS) in species with complex genomes can focus on genic and promoter regions [ABSTRACT FROM AUTHOR]

The brain-derived neurotrophic factor (BDNF) gene is critical for neuronal function and survival, and is likely to be important in psychiatric disorders. In this study, we used single-nucleotide polymorphism (SNP) discovery, functional analyses, and genetic association studies to better understand the potential role of BDNF sequence variation in behavior. Screening 480 unrelated individuals for SNPs and genotyping was performed in US Caucasian, American Indian, and African American populations. Lifetime DSM-III-R psychiatric diagnoses were assigned and the Tridimensional Personality Questionnaire (TPQ) was administered to measure anxious temperament (harm avoidance (HA)) and novelty seeking (NS). A novel SNP (-281 C > A) in promoter 1 was discovered that had decreased DNA binding in vitro and decreased basal reporter gene activity in transfected rat hippocampal neurons. The frequency of the -281 A allele was 0.03 in a Caucasian sample, but was virtually absent in other populations. Association analyses in a community-based sample showed that individuals with the -281 A allele (13 heterozygotes) had lower TPQ HA (F = 4.8, p < 0.05). In contrast, the Met 66 allele was associated with increased HA (F- 4.1, p = 0.02) and was most abundant in individuals with both anxiety disorders and major depression (p < 0.05). Among the Val66Val homozygotes, individuals who were -281 CA heterozygotes had significantly lower HA than the -281 CC homozygotes (p < 0.01). Our results suggest that in this population, the Iow activity -281 A allele may be protective against anxiety and psychiatric morbidity, whereas Met 66 may be a risk allele. [ABSTRACT FROM AUTHOR]