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PubMed1992

Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter.

Circular muscle strips from opossum lower esophageal sphincter were suspended in organ baths for measurement of isometric tension. Nonadrenergic noncholinergic (NANC) inhibitory nerves were stimulated by means of transmural field stimulation. This induced frequency-dependent relaxations of the muscle strips. Methylene blue (3 x 10(-6) M; inhibits guanylate cyclase) and pyrogallol (10(-4) M; generates superoxide anions) had no influence on relaxations, whereas oxyhemoglobin [10(-5) M; binds nitric oxide (NO) and other nitroso compounds extracellularly] inhibited relaxations at all frequencies. NO concentration dependently relaxed the muscle strips. Pyrogallol (10(-4) M) and methylene blue (3 x 10(-6) M) inhibited and oxyhemoglobin (10(-5) M) nearly abolished relaxation induced by NO. S-nitroso-L-cysteine caused concentration-dependent relaxations of the muscle strips, which were inhibited by pyrogallol (10(-4) M), whereas methylene blue (3 x 10(-6) M) augmented the action of S-nitroso-L-cysteine. Methylene blue (3 x 10(-6) M) had no influence on the concentration-dependent relaxations caused by sodium nitroprusside (SNP). Oxyhemoglobin (10(-5) M), and to a lesser extent pyrogallol (10(-4) M), both inhibited the effects of SNP. The action profiles for S-nitroso-L-cysteine, NO, and SNP differed from the action profile for NANC nerve-mediated response. Although pyrogallol inhibited the effects of SNP, the action profile generally resembled the action profile for NANC responses more closely than did the profiles for S-nitroso-L-cysteine or NO. In conclusion, of the nitroso compounds studied, SNP most closely resembled the response to NANC nerve stimulation. Neither NO nor S-nitroso-L-cysteine individually mimicked the NANC response.

Animals↗

PubMed2004

A double classification tree search algorithm for index SNP selection.

BACKGROUND: In population-based studies, it is generally recognized that single nucleotide polymorphism (SNP) markers are not independent. Rather, they are carried by haplotypes, groups of SNPs that tend to be coinherited. It is thus possible to choose a much smaller number of SNPs to use as indices for identifying haplotypes or haplotype blocks in genetic association studies. We refer to these characteristic SNPs as index SNPs. In order to reduce costs and work, a minimum number of index SNPs that can distinguish all SNP and haplotype patterns should be chosen. Unfortunately, this is an NP-complete problem, requiring brute force algorithms that are not feasible for large data sets. RESULTS: We have developed a double classification tree search algorithm to generate index SNPs that can distinguish all SNP and haplotype patterns. This algorithm runs very rapidly and generates very good, though not necessarily minimum, sets of index SNPs, as is to be expected for such NP-complete problems. CONCLUSIONS: A new algorithm for index SNP selection has been developed. A webserver for index SNP selection is available at http://cognia.cu-genome.org/cgi-bin/genome/snpIndex.cgi/

Algorithms↗

PubMed2005

Comparative linkage analysis and visualization of high-density oligonucleotide SNP array data.

BACKGROUND: The identification of disease-associated genes using single nucleotide polymorphisms (SNPs) has been increasingly reported. In particular, the Affymetrix Mapping 10 K SNP microarray platform uses one PCR primer to amplify the DNA samples and determine the genotype of more than 10,000 SNPs in the human genome. This provides the opportunity for large scale, rapid and cost-effective genotyping assays for linkage analysis. However, the analysis of such datasets is nontrivial because of the large number of markers, and visualizing the linkage scores in the context of genome maps remains less automated using the current linkage analysis software packages. For example, the haplotyping results are commonly represented in the text format. RESULTS: Here we report the development of a novel software tool called CompareLinkage for automated formatting of the Affymetrix Mapping 10 K genotype data into the "Linkage" format and the subsequent analysis with multi-point linkage software programs such as Merlin and Allegro. The new software has the ability to visualize the results for all these programs in dChip in the context of genome annotations and cytoband information. In addition we implemented a variant of the Lander-Green algorithm in the dChipLinkage module of dChip software (V1.3) to perform parametric linkage analysis and haplotyping of SNP array data. These functions are integrated with the existing modules of dChip to visualize SNP genotype data together with LOD score curves. We have analyzed three families with recessive and dominant diseases using the new software programs and the comparison results are presented and discussed. CONCLUSIONS: The CompareLinkage and dChipLinkage software packages are freely available. They provide the visualization tools for high-density oligonucleotide SNP array data, as well as the automated functions for formatting SNP array data for the linkage analysis programs Merlin and Allegro and calling these programs for linkage analysis. The results can be visualized in dChip in the context of genes and cytobands. In addition, a variant of the Lander-Green algorithm is provided that allows parametric linkage analysis and haplotyping.

Family Health↗

PubMed2004

Detecting imbalanced expression of SNP alleles by minisequencing on microarrays.

BACKGROUND: Each of the human genes or transcriptional units is likely to contain single nucleotide polymorphisms that may give rise to sequence variation between individuals and tissues on the level of RNA. Based on recent studies, differential expression of the two alleles of heterozygous coding single nucleotide polymorphisms (SNPs) may be frequent for human genes. Methods with high accuracy to be used in a high throughput setting are needed for systematic surveys of expressed sequence variation. In this study we evaluated two formats of multiplexed, microarray based minisequencing for quantitative detection of imbalanced expression of SNP alleles. We used a panel of ten SNPs located in five genes known to be expressed in two endothelial cell lines as our model system. RESULTS: The accuracy and sensitivity of quantitative detection of allelic imbalance was assessed for each SNP by constructing regression lines using a dilution series of mixed samples from individuals of different genotype. Accurate quantification of SNP alleles by both assay formats was evidenced for by R2 values > 0.95 for the majority of the regression lines. According to a two sample t-test, we were able to distinguish 1-9% of a minority SNP allele from a homozygous genotype, with larger variation between SNPs than between assay formats. Six of the SNPs, heterozygous in either of the two cell lines, were genotyped in RNA extracted from the endothelial cells. The coefficient of variation between the fluorescent signals from five parallel reactions was similar for cDNA and genomic DNA. The fluorescence signal intensity ratios measured in the cDNA samples were compared to those in genomic DNA to determine the relative expression levels of the two alleles of each SNP. Four of the six SNPs tested displayed a higher than 1.4-fold difference in allelic ratios between cDNA and genomic DNA. The results were verified by allele-specific oligonucleotide hybridisation and minisequencing in a microtiter plate format. CONCLUSIONS: We conclude that microarray based minisequencing is an accurate and accessible tool for multiplexed screening for imbalanced allelic expression in multiple samples and tissues in parallel.

Alleles↗

PubMed2003

A strategy for detection of known and unknown SNP using a minimum number of oligonucleotides applicable in the clinical settings.

Detection of unknown single nucleotide polymorphism (SNP) relies on large scale sequencing expeditions of genomic fragments or complex high-throughput chip technology. We describe a simplified strategy for fluorimetric detection of known and unknown SNP by proportional hybridization to oligonucleotide arrays based on optimization of the established principle of signal loss or gain that requires a drastically reduced number of matched or mismatched probes. The array consists of two sets of 18-mer oligonucleotide probes. One set includes overlapping oligos with 4-nucleotide tiling representing an arbitrarily selected "consensus" sequence (consensus-oligos), the other includes oligos specific for known SNP within the same genomic region (variant-oligos). Fluorescence-labeled DNA amplified from a homozygous source identical to the consensus represents the reference target and is co-hybridized with a differentially-labeled test sample. Lack of hybridization of the test sample to consensus- with simultaneous hybridization to variant-oligos designates a known allele. Lack of hybridization to consensus- and variant-oligos indicates a new allele. Detection of unknown variants in heterozygous samples depends upon fluorimetric analysis of signal intensity based on the principle that homozygous samples generate twice the amount of signal. This method can identify unknown SNP in heterozygous conditions with a sensitivity of 82% and specificity of 90%. This strategy should dramatically increase the efficiency of SNP detection throughout the human genome and will decrease the cost and complexity of applying genomic wide analysis in the context of clinical trials.

Journal Article↗

PubMed2006

Inferring loss-of-heterozygosity from unpaired tumors using high-density oligonucleotide SNP arrays.

Loss of heterozygosity (LOH) of chromosomal regions bearing tumor suppressors is a key event in the evolution of epithelial and mesenchymal tumors. Identification of these regions usually relies on genotyping tumor and counterpart normal DNA and noting regions where heterozygous alleles in the normal DNA become homozygous in the tumor. However, paired normal samples for tumors and cell lines are often not available. With the advent of oligonucleotide arrays that simultaneously assay thousands of single-nucleotide polymorphism (SNP) markers, genotyping can now be done at high enough resolution to allow identification of LOH events by the absence of heterozygous loci, without comparison to normal controls. Here we describe a hidden Markov model-based method to identify LOH from unpaired tumor samples, taking into account SNP intermarker distances, SNP-specific heterozygosity rates, and the haplotype structure of the human genome. When we applied the method to data genotyped on 100 K arrays, we correctly identified 99% of SNP markers as either retention or loss. We also correctly identified 81% of the regions of LOH, including 98% of regions greater than 3 megabases. By integrating copy number analysis into the method, we were able to distinguish LOH from allelic imbalance. Application of this method to data from a set of prostate samples without paired normals identified known regions of prevalent LOH. We have developed a method for analyzing high-density oligonucleotide SNP array data to accurately identify of regions of LOH and retention in tumors without the need for paired normal samples.

Alleles↗

PubMed2005

High-throughput SNP genotyping by single-tube PCR with Tm-shift primers.

Despite many recent advances in high-throughput single nucleotide polymorphism (SNP) genotyping technologies, there is still a great need for inexpensive and flexible methods with a reasonable throughput. Here we report substantial modifications and improvements to an existing homogenous allele-specific PCR-based SNP genotyping method, making it an attractive new option for researchers engaging in candidate gene studies or following up on genome-wide scans. In this advanced version of the melting temperature (Tm)-shift SNP genotyping method, we attach two GC-rich tails of different lengths to allele-specific PCR primers, such that SNP alleles in genomic DNA samples can be discriminated by the Tms of the PCR products. We have validated 306 SNP assays using this method and achieved a success rate in assay development of greater than 83% under uniform PCR conditions. We have developed a standalone software application to automatically assign genotypes directly from melting curve data. To demonstrate the accuracy of this method, we typed 592 individuals for 6 SNPs and showed a high call rate (>98%) and high accuracy (>99.9%). With this method, 6-10,000 samples can be genotyped per day using a single 384-well real-time thermal cycler with 2-4 standard 384-well PCR instruments.

DNA Primers↗

PubMed2003

Designing an optimum genetic association study using dense SNP markers and family-based sample.

Genetic association analysis using thousands of single nucleotide polymorphism (SNP) markers has become a promising alternative to genome-wide linkage scan. Analysis based on linkage-disequilibrium (LD) is more efficient because meiotic information of past generations is utilized. However, in addition to the physical distance between the disease locus and a marker locus, numerous other factors such as admixture, genetic drift, and multiple mutations can affect the observed value of LD. The effect of these factors in a genomic LD association study must be carefully analyzed to obtain an efficient study design. In the following review, we consider studies using family-based data and carefully study the effects of some of these important design factors, including the sample size, frequency of SNP markers, and marker density. For example, we conclude that (1) for reasonably frequent SNP markers, a moderately large sample of 500 families is appropriate for a moderately stringent significance level (alpha = 0.00009); (2) to maintain a power of 80%, maximal difference in allele frequencies between the disease gene and a SNP marker varies between 0.1 (under additive model) and 0.5 (multiplicative); (3) a map density of 10 cM is appropriate only under idea scenario (moderately large sample size, equal trait/marker allele frequencies, maximum LD strength etc.). Results shown here should have practical implications to designing efficient LD association studies using dense SNP markers.

Epidemiologic Research Design↗

PubMed2004

[Effects of SNP and L-NAME on spermatogenesis in rats].

OBJECTIVE: To observe the effects of nitric oxide(NO) on the DNA ploidy of germ cells and to evaluate the role of NO in modulating spermatogenesis by using SNP, a donor of NO and N-nitro-l-arginine-mythel-ester(L-NAME), an inhibitor of nitric oxide synthese(NOS) in rats physically in vivo. METHODS: Forty adult male, Sprague-Dawley rats (60-70 days) were divided into four groups, and injected ultraperitoneally with one of the following agents (once a day, for 12 days): SNP, L-NAME and SNP + L-NAME with normal saline. Two hours after the last injection the rats were sacrificed. The sera were collected and stored at -70 degrees C for subsequent hormone assay. The concentration of serum testosterone was measured by radioimmunoassay. Serum NOx- (nitrite/nitrate) concentration was measured by Greiss method. DNA of spermatogenic cells was detected by flow cytometry(FCM), and the percentage of 1c, 2c and 4c germ cells calculated. RESULTS: In the SNP treatment group, the serum concentration of NOx- was higher, testosterone concentration was lower and the number of 1c cells was smaller compared with the control group. However, in rats treated with L-NAME, the concentration of NOx- was significantly lower, testosterone concentration was higher and the number of 1c cells was larger compared with the control group(P < 0.01). No changes were observed in the SNP + L-NAME group. CONCLUSION: Enhancing ectogenous NO will suppress spermatogenesis while inhibiting NO productive pathway will promote it.

Animals↗

PubMed2005

[A simple and rapid modified--new method for SNP typing by fragment length discrepant allele specific PCR].

OBJECTIVE: To establish a new method for single nucleotide polymorphism (SNP) typing based on allele specific PCR: fragment length discrepant allele specific PCR (FLDAS-PCR), and study the influence on specific extension by introducing a mismatch at the third or fourth 3'-terminal base of allele specific primers. METHODS: For SNP loci rs759117 and rs760887, two allele specific forward primers, with different length and a mismatch introduced at the third or fourth 3'-terminal base, and a public reverse primer were designed for SNP typing. The genotyping of SNP was determined by the two allele specific fragments different in size after polyacrylamide gel and silver staining. RESULTS: The different homozygote genotypes comprised a single band with different size respectively, and the heterozygote genotypes comprised two bands. Typing results were completely consistent with those by direct sequencing. Non-specific primer extension was decreased remarkably after introducing a mismatch at the third or fourth 3'-terminal base of allele specific primers, and the stringency of PCR reaction was cut down. CONCLUSION: FLDAS-PCR is a simple, rapid and efficient new method for SNP typing. During FLDAS-PCR, specific primers with a mismatch at the third or fourth 3'-terminal base have more power to identify two alleles.

Alleles↗

PubMed2006

[Single nucleotide polymorphism (SNP) and its application in rice].

Single nucleotide polymorphisms (SNPs) distribute numerously and high-density throughout rice (Oryza sativa L.) genome. A total of 80,127 SNP sites were identified in rice genome, and one SNP every 154 bp was found between two rice subspecies indica and japonica. The SNP rate is 0.65%. SNPs also are very considerable among within-subspecies cultivars, even it can be found between closely related cultivars, in which it has been difficult to find polymorphic sites by conventional methods. The frequency of SNPs in rice genome varied between chromosomes, moreover it showed uneven distribution of polymorphism-rich and -poor regions along each chromosome. Several routes have been used for identification of SNP in rice, such as sequencing PCR products of DNA samples, screening SNPs in SSR fragments, and searching for SNPs through the rice genome sequences and EST database. A number of genotyping systems have been developed to identify SNPs in rice genome. High automation in SNPs identification has become a very convenient operation by the automatized systems. SNPs can be converted to CAPS (cleaved amplified polymorphic sequence) or dCAPS (derived-CAPS), and allele-specific PCR markers. SNP has shown huge potential in establishing rice genetic maps, genes cloning and functional genomics, MAS (marker assisted selection) in rice breeding, and studying on classification and evolution of germplasm.

Breeding↗

PubMed2005

Direct analysis of unphased SNP genotype data in population-based association studies via Bayesian partition modelling of haplotypes.

We describe a novel method for assessing the strength of disease association with single nucleotide polymorphisms (SNPs) in a candidate gene or small candidate region, and for estimating the corresponding haplotype relative risks of disease, using unphased genotype data directly. We begin by estimating the relative frequencies of haplotypes consistent with observed SNP genotypes. Under the Bayesian partition model, we specify cluster centres from this set of consistent SNP haplotypes. The remaining haplotypes are then assigned to the cluster with the "nearest" centre, where distance is defined in terms of SNP allele matches. Within a logistic regression modelling framework, each haplotype within a cluster is assigned the same disease risk, reducing the number of parameters required. Uncertainty in phase assignment is addressed by considering all possible haplotype configurations consistent with each unphased genotype, weighted in the logistic regression likelihood by their probabilities, calculated according to the estimated relative haplotype frequencies. We develop a Markov chain Monte Carlo algorithm to sample over the space of haplotype clusters and corresponding disease risks, allowing for covariates that might include environmental risk factors or polygenic effects. Application of the algorithm to SNP genotype data in an 890-kb region flanking the CYP2D6 gene illustrates that we can identify clusters of haplotypes with similar risk of poor drug metaboliser (PDM) phenotype, and can distinguish PDM cases carrying different high-risk variants. Further, the results of a detailed simulation study suggest that we can identify positive evidence of association for moderate relative disease risks with a sample of 1,000 cases and 1,000 controls.

Algorithms↗

PubMed2003

Enhanced allele-specific PCR discrimination in SNP genotyping using 3' locked nucleic acid (LNA) primers.

The specificity and reliability of locked nucleic acid (LNA) substitution at the 3' position of allele-specific PCR (AS-PCR) primers for SNP detection was investigated in direct comparison to DNA primers. Both plasmid and human genomic DNA templates were examined in this study. All possible DNA and 3' LNA mismatch combinations were tested in triplicate with the plasmid target. LNA primers yield consistently low amounts of mismatch products with all base combinations, whereas certain mismatches with DNA primers generate strong false positive amplicons. Amplified human SNP alleles within the cystic fibrosis (CFTR) gene were analyzed in AS-PCR by gel analysis and real-time fluorescence generation. A 3' LNA residue in the primer at the SNP site improves allelic discrimination and functions under a wide window of PCR conditions. We demonstrate increased AS-PCR specificity with comparable sensitivity using 3' LNA primers in gel electrophoresis and real-time detection experiments. This increase in AS-PCR discrimination with 3' LNA primers should facilitate the use of this simple, rapid, and inexpensive technique for SNP genotyping applications.

Alleles↗

PubMed2004

Comparison of four flow cytometric SNP detection assays and their use in plant improvement.

Single nucleotide polymorphisms (SNPs) are attractive DNA markers due to their abundance and potential for use in automated high-throughput genotyping. Numerous SNP genotyping assays have been developed, but it is unclear which assays are best suited and most efficient for various types of plant improvement research. The objective of this study was to compare the accuracy, efficiency, and cost of four SNP genotyping assays: single-base extension (SBE), allele-specific primer extension (ASPE), oligonucleotide ligation (OL), and direct hybridization (DH). All four assay methods used the same Luminex 100 flow cytometer platform. Fifty-eight F(2)-derived soybean [Glycine max (L.) Merr.] lines from a cross between inbred lines G99-G725 and N00-3350 were genotyped at four SNPs. SBE and ASPE clearly differentiated between the two homozygotes and the heterozygote at each SNP. Results were in agreement with those identified using the SNaPshot minisequencing assay as a control. In contrast, the OL and DH assays were unable to differentiate between genotypes at some of the SNPs. However, when the cost per data point for the four different assays was compared, the cost of OL and DH was only about 70% of that for SBE, with DH requiring the least time of the four assays. On the basis of cost and labor, ASPE is more cost-effective and simpler than SBE, and would therefore be a good method for genetic mapping and diversity studies which require a large number of markers and a high level of multiplexing. DH appears to be the most economical assay for marker-assisted selection, though optimization for DH would be required for some SNP markers.

Base Sequence↗

PubMed2006

Identification of new single nucleotid polymorphisms (SNP) in alcohol dehydrogenase class IV ADH7 gene within a French population.

Many epidemiological studies have explored the possible link between the susceptibility to alcohol related cancers, such as oesophageal cancers, and genetic variants of alcohol dehydrogenases (ADHs). Alcohol dehydrogenase class IV ADH7 is mainly expressed in the upper aero-digestive tract and is involved in the first pass ethanol metabolism. As far as we know, no study has described single nucleotide polymorphisms (SNPs) within ADH7 exons in the Caucasian population. Therefore, in a pilot study, we used the denaturing high performance liquid chromatography (DHPLC) method to screen 49 oesophageal cancer cases for SNPs in the ADH7 gene. A total of 5 SNPs was observed in this study: one SNP in the 5' non-translated regions of exon 1, two SNPs in introns 3 and 4 and two others SNPs in exons 3 and 4. The SNP located in the exon 1, which has never been described before, occurred in a reverse TATA box whereas the SNP of exon 3 was a non-silent polymorphism. Because these two SNPs could potentially affect the transcription and/or the enzyme activity, their distribution was evaluated in a representative sample of healthy Caucasians (n = 89) recruited in Lower Normandy. Frequencies of heterozygous samples ranged from 11% (exon 3) to 28% (exon 1). No homozygous samples were found. In this pilot study, the DHPLC method was suitable for both SNP screening and genotyping and allowed the detection of five SNPs in the ADH7 gene, two of which have never been described before, among the European population.

Alcohol Dehydrogenase↗

PubMed1999

Single nucleotide polymorphism (SNP) discovery and linkage mapping of bovine cytokine genes.

Polymorphic markers at bovine gene loci facilitate the integration of cattle genetic maps with those of humans and mice. To this end, 31 single nucleotide polymorphism (SNP) markers were developed for seven bovine chemokine genes. Loci were amplified from bovine genomic DNA by the polymerase chain reaction, and candidate amplicons were sequenced to determine their identity. Amplified loci from 24 founding parents and select progeny from a beef cattle reference population were sequenced and analyzed for SNPs. SNP haplotype alleles were determined by examining segregation patterns and used to establish the locus position on the bovine linkage map. Loci for growth-related proteins (GRO3, GRO1, and GROX) were clustered with the related CXC chemokine genes, interleukin (IL) 8, and epithelial cell inflammatory protein 1, at 84 cM from the centromeric end of the bovine chromosome (BTA) 6 linkage group. Bovine loci for a cluster of IL8 receptors, a stromal cell-derived factor 1, interferon-gamma, and tumor necrosis factor-alpha were mapped at 90, 55, 59, and 34 cM, respectively, from the centromeric ends of the BTA 2, 28, 5, and 23 linkage groups. The positions of these bovine loci were compared with those of orthologous loci on the human map to refine the boundaries of conserved synteny. These seven loci provide examples of SNP development in which the efficiency was largely dependent on the availability of bovine genomic or cDNA sequence. The polymorphic nature of these SNP haplotype markers suggests that they will be useful for mapping complex traits in cattle, such as resistance to infectious disease.

Animals↗

PubMed2005

Comprehensive genetic evaluation of common E-cadherin sequence variants and prostate cancer risk: strong confirmation of functional promoter SNP.

The E-cadherin gene (CDH1) has been proposed as a prostate cancer (PC) susceptibility gene in several studies. Aberrant protein expression has been related to prognosis and progression in PC. In addition, a functional promoter SNP (rs16260) has been found to associate with PC risk. We performed a comprehensive genetic analysis of CDH1 by using the method of haplotype tagged SNPs in a large Swedish population-based case-control study consisting of 801 controls and 1,636 cases. In addition, Swedish PC families comprising a total of 157 cases sampled for DNA were analyzed for selected SNPs. Seven SNPs, including the promoter SNP rs16260, that captured over 96% of CDH1 haplotype variation were selected as haplotype tagging SNPs and analyzed for associated PC risk. We observed significant confirmation of rs16260 (P=0.003) for cases with a positive family history of PC (FH+) both in an independent case-control population and in PC families. In addition, a common haplotype (HapB, 25%) including the variant allele of rs16260 was associated (P=0.004) with PC risk among FH+ cases. The promoter SNP rs16260 as well as HapB were significantly transmitted to affected offspring in PC families. We report strong confirmation of the association between PC risk in FH+ cases and a functional CDH1 promoter SNP in an independent population. In conjunction with the biological importance of CDH1 our findings encourage further evaluation of genetic variation in CDH1 in relation to PC etiology. Due to the difficulties in replication of genetic association studies, this finding is unusual and novel.

Adult↗

PubMed2006

Similarity of the allele frequency and linkage disequilibrium pattern of single nucleotide polymorphisms in drug-related gene loci between Thai and northern East Asian populations: implications for tagging SNP selection in Thais.

The similarity of the marker allele frequency and linkage disequilibrium structure between two populations are major factors for the determination of the transferability and efficiency of haplotype tagging SNP derived from one population to use for an indirect association study in another population. To prove the similarity between northern East Asian populations in Hapmap and Thais, 861 SNP in 166 drug-related genes shared between Thais, Han Chinese and Japanese were analyzed for their correlation statistics. Allele frequency, Fst statistics and linkage disequilibrium statistics (r (2)) showed a high correlation between these populations. TagSNP sets derived by an aggressive tagging algorithm from these 861 SNP in Japanese and Chinese were used to test the coverage of East Asia-derived tagSNP in Thais. TagSNP derived from Japanese and Chinese are comparable in the percentage of coverage of the alleles captured with tagSNP at r (2)>or=0.8 (93% vs. 93%) in these drug-related gene loci. Additional tagSNP sets derived from the combination of Japanese- and Chinese-derived tagging SNP sets were used to test the coverage in Thais. The later set improved the percentage of coverage of alleles captured with tagSNP at r (2)>or=0.8-98% for these sites. High similarity between Thais and northern East Asian allele frequency and linkage disequilibrium statistics supported that tagSNPs derived from the northern East Asian population should be useful for an indirect association study in Thais. The combination of non-overlapping Japanese derived tagSNP and Chinese-derived tagSNP improved the percentage of genomic coverage in Thais, at least in these drug-related gene loci.

Algorithms↗