Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “single nucleotide polymorphisms”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources
PubMed2006

Novel single nucleotide polymorphism of UGT1A7 gene in Japanese.

We sequenced exon 1 of the UDP-glucuronosyltransferase (UGT) 1A7 gene from 52 Japanese cancer patients. Four single nucleotide polymorphisms (SNPs) were found. Three of them caused UGT1A7*2 and UGT1A7*3. A novel SNP (98973G>C) causing amino acid substitution (Ser141Cys) was found. The sequence is as follows: SNP, 050824FujitaK002; Gene Name, UGT1A7; Accession Number, AF297093; Length, 25 bases; 5'-TAAAGGAGAGTTG/CTTTTGATGCAGT-3'. One out of 52 cancer patients was heterozygous for the variant allele, resulting in the allele frequency of 0.96%. The patient did not possess UGT1A7*2 or UGT1A7*3.

Alleles↗
PubMed2004

Single nucleotide polymorphism in the 5' tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients.

Thymidylate synthase (TS) is the primary target of 5-fluorouracil (5-FU). A VNTR polymorphism in the TS promoter region is associated with the efficacy of 5-FU-based chemotherapy in colorectal cancer. A common G>C SNP at the 12th nucleotide of the second repeat in the TS*3 alleles has been recently described. The combination of SNP and VNTR allows the definition of 3 TS alleles: *2, *3G and *3C. The aim of our study was to evaluate the predictive value of clinical response and survival of these new defined TS alleles. TS genotypes of 89 patients diagnosed with metastatic colorectal cancer and undergoing 5-FU-based chemotherapy were carried out. The clinical outcome was evaluated according to the genotype (high expression genotype: *2R/*3G; *3C/*3G; *3G/*3G; and low expression genotype: *2R/*2R; *2R/*3C; *3C/*3C. A higher overall response was observed in the group of patients with a low expression genotype (p = 0.035). The probability of achieving a clinical response of patients with a low expression-related genotype was 2.9 higher than that of the other group (95% CI = 1.03-5.6, p = 0.04). The median time to progression was 12 months and 9 months in the low and high expression groups, respectively (p = 0.07, log rank test). Overall survival was significantly longer in the low expression group. In this group the median OS was not achieved at 50 months of follow-up in contrast to the 20 months observed in the high expression group (p = 0.03). TS genotype was an independent predictor of progression-free and overall survival in the Cox regression models after adjustment to the other clinical variables. The selection of patients who are likely to respond to 5-FU therapy may be considerably improved if the TS genotype were to include both the VNTR and the SNP located within the promoter region of the gene.

Adult↗
PubMed2004

Role of single nucleotide polymorphisms of pro-inflammatory cytokine genes in the relationship between serum lipids and inflammatory parameters, and the lipid-lowering effect of fish oil in healthy males.

BACKGROUND AND AIMS: Lipid metabolism, obesity and inflammation are intimately related. Plasma triglycerides increase during the inflammatory response to pathogens and obesity increases inflammatory stress. Pro-inflammatory cytokines are secreted by adipocytes in uninfected obese subjects. Polymorphisms (SNPs) in cytokine genes influence the intensity of cytokine production and inflammatory stress. Fish oil has lipid-lowering and anti-inflammatory properties. The influence of cytokine gene polymorphisms on the interaction between adiposity, inflammation and the properties of fish oil is unknown. METHODS: Fasting plasma triglycerides, acute phase proteins and BMI were studied in 159 healthy men and the effect of 6 g/d fish oil for 12 weeks on the former two parameters studied. Subjects were genotyped for SNPs at positions -511, -174, +252 and -308 in the IL-1beta, IL-6, LT-alpha (TNF-beta) and TNF-alpha genes, respectively. Data were divided into three sub-groups of BMI, 16.7-22.8, 22.9-24.9 and 25.1-33.7 kg/m2, respectively. RESULTS: Correlations were apparent between CRP and triglycerides in the highest tertile r = 0.324, P < 0.05 and between CRP and serum amyloid in all tertiles. Mean concentrations of all three molecules were higher in the middle and highest tertile than in the lowest. Irrespective of BMI, CRP and triglycerides were positively correlated in subjects with a TNF-alpha-308GG, LT-alpha AG, IL-1beta-511TT and IL-6-174GG genotype. The latter three genotypes are associated with enhanced inflammation. Genotype and BMI interacted. Concentrations of triglyceride rose significantly with increasing tertile only in subjects with a LT-alpha AA genotype. CRP concentrations rose in subjects with a LT-alpha AG genotype. Triglycerides were lowered by fish oil. Pre-supplementation concentrations were correlated with the decrease, r = -0.494 P < 0.0001. Genotype influenced the effects of fish oil. A fall occurred in triglycerides, across tertiles of BMI, only in individuals possessing a LT-alpha+252 AA genotype. Irrespective of BMI, possession of an A allele of this SNP was necessary for the correlation to occur. CONCLUSIONS: Possession of genotypes associated with raised inflammatory stress strengthen the association between fasting plasma triglycerides and CRP. The ability of fish oil to exert a lipid-lowering, anti-inflammatory influence in healthy men is influenced by BMI and possession of the LT-alpha+252 A allele.

Acute-Phase Proteins↗
PubMed2005

A new single nucleotide polymorphism in CAPN1 extends the current tenderness marker test to include cattle of Bos indicus, Bos taurus, and crossbred descent.

The three objectives of this study were to 1) test for the existence of beef tenderness markers in the CAPN1 gene segregating in Brahman cattle; 2) test existing CAPN1 tenderness markers in indicus-influenced crossbred cattle; and 3) produce a revised marker system for use in cattle of all subspecies backgrounds. Previously, two SNP in the CAPN1 gene have been described that could be used to guide selection in Bos taurus cattle (designated Markers 316 and 530), but neither marker segregates at high frequency in Brahman cattle. In this study, we examined three additional SNP in CAPN1 to determine whether variation in this gene could be associated with tenderness in a large, multisire American Brahman population. One marker (termed 4751) was associated with shear force on postmortem d 7 (P < 0.01), 14 (P = 0.015), and 21 (P < 0.001) in this population, demonstrating that genetic variation important for tenderness segregates in Bos indicus cattle at or near CAPN1. Marker 4751 also was associated with shear force (P < 0.01) in the same large, multisire population of cattle of strictly Bos taurus descent that was used to develop the previously reported SNP (referred to as the Germplasm Evaluation [GPE] Cycle 7 population), indicating the possibility that one marker could have wide applicability in cattle of all subspecies backgrounds. To test this hypothesis, Marker 4751 was tested in a third large, multisire cattle population of crossbred subspecies descent (including sire breeds of Brangus, Beefmaster, Bonsmara, Romosinuano, Hereford, and Angus referred to as the GPE Cycle 8 population). The highly significant association of Marker 4751 with shear force in this population (P < 0.001) confirms the usefulness of Marker 4751 in cattle of all subspecies backgrounds, including Bos taurus, Bos indicus, and crossbred descent. This wide applicability adds substantial value over previously released Markers 316 and 530. However, Marker 316, which had previously been shown to be associated with tenderness in the GPE Cycle 7 population, also was highly associated with shear force in the GPE Cycle 8 animals (P < 0.001). Thus, Marker 316 may continue to be useful in a variety of populations with a high percentage of Bos taurus backgrounds. An optimal marker strategy for CAPN1 in many cases will be to use both Markers 316 and 4751.

Animals↗
PubMed2003

Identification of novel single nucleotide polymorphisms within the NOTCH4 gene and determination of association with MHC alleles.

Mapping of disease susceptibility loci within the MHC has been partly hampered by the high degree of polymorphism of the HLA genes and the high level of linkage disequilibrium (LD) between markers within the MHC region. It is therefore important to identify new markers and determine the level of LD between HLA alleles and non-HLA genes. The NOTCH4 gene lies at the centromeric end of the MHC class III region, approximately 335 kb telomeric of the DRB1 locus. The encoded protein is an oncogene that is important in regulating vascular development and remodelling. A recent report has linked polymorphisms within NOTCH4 with risk of developing schizophrenia. We have investigated if coding polymorphisms exist within this gene and have identified three single nucleotide polymorphisms; a synonomous T to C transition at +1297 (HGBASE accession number SNP000064386), a synonomous A to G transition at +3061 (SNP000064387) and an A to G transition at +3063 which results in a replacement of glycine with aspartic acid at amino acid 279 (SNP000064388). The allele frequencies of +1297T, +3061A and +3063G were 0.65, 0.66 and 0.66, respectively. Linkage disequilibrium was detected both between these markers and with MHC alleles. These findings can be used in the fine mapping of disease susceptibility alleles within the MHC.

Humans↗
PubMed2006

Association of a single nucleotide polymorphism in the calpastatin gene with carcass and meat quality traits of beef cattle.

Calpastatin (CAST) is a naturally occurring protein that inhibits the normal tenderization of meat as it ages postmortem. A SNP was identified in the CAST gene (a G to C substitution) and genotyped on crossbred commercially fed heifers (n = 163), steers (n = 226), and bulls (n = 61) from beef feedlots, and steers (n = 178) from a University of Guelph feeding trial. The association of the CAST SNP with carcass and meat quality traits was studied. Carcass traits included fat, lean, and bone yield; grade fat; LM area; and HCW. Meat quality traits included marbling grade; i.m. fat content of LM; tenderness evaluation of LM (Warner-Bratzler shear force) at 2, 7, 14, and 21 d of postmortem aging; and tenderness evaluation of semitendinosus muscle at 7 d of postmortem aging. The mixed model used in the analyses included fixed effects of CAST genotype, sex, slaughter group, and breed composition (linear covariate); sire was a random effect. For the analysis of shear force, i.m. fat content of LM was also included in the model as a linear covariate. Shear force measures were analyzed within days of postmortem aging and by repeated measures analysis. The CAST SNP allele C was more frequent (63%) in the crossbred population than allele G. The CAST SNP was associated with shear force across days of postmortem aging (P = 0.005); genotype CC yielded beef that was more tender than GG (-0.32 kg +/- 0.13), and CG had intermediate tenderness. The corresponding average allele substitution effect (G to C substitution) was also highly significant (-0.15 +/- 0.05 kg, P = 0.002). A lower percentage of unacceptably tough steaks (shear force > 5.7 kg) at 2 and 7 d postmortem was associated with an increasing number of C alleles (P < or = 0.05). At 7 d postmortem, the percentage of unacceptably tough steaks decreased by 24 and 35%, respectively, for animals carrying 1 and 2 copies of the C allele relative to animals with no C alleles. However, genotype CC had a greater fat yield (+1.44 +/- 0.56%; P = 0.037) than genotype GG, with a corresponding allele substitution effect of 0.67 +/- 0.27% (P = 0.015). Therefore, the CAST SNP allele C was associated with increased LM tenderness across days of postmortem aging and, importantly for the beef industry, had a significant reduction in the percentage of steaks rated unacceptably tough by consumers based on an assumed threshold level.

Animals↗
PubMed2006

Quantitative analysis of chimerism after allogeneic stem cell transplantation by real-time polymerase chain reaction with single nucleotide polymorphisms, standard tandem repeats, and Y-chromosome-specific sequences.

We compared the results of chimerism analyses with real-time SNP-PCR to those obtained by the classical STR-PCR method in 135 hematopoietic stem cell transplantation recipients. Using 10 different SNP gene loci, the SNP-PCR method was able to discriminate patient from donor cells in 125 of 135 cases (93%), whereas the use of 11 different STR gene loci with the STR-PCR analysis using agarose or polyacrylamide gel resolution resulted in accurate donor-host discrimination in all patients. Of the 470 analyzed samples we found in 74% concordant results for both chimerism methods. In all 26% discordant cases the SNP-chimerism method showed mixed chimerism (MC), whereas the STR-method found complete chimerism (CC). As a consequence, the SNP-PCR chimerism analysis method detected a MC prior to the occurrence of relapse significantly earlier than the STR-PCR chimerism method (120 vs. 30 days, P < 0.007). The probability of relapses was significantly higher in patients with increasing MC (70%) compared to 30% in patients with CC (P < 0.00001) associated with a significantly shorter overall survival in patients with increasing MC. The multivariate Cox model showed that chimerism analsis with SNP-PCR was the only significant risk factor predicting relapse (RR 6.08, P < 0.0001).Furthermore, we analyzed the chimerism status in male recipients with a female donor in 580 samples of 134 patients using quantitative real-time PCR of Y-chromosome-specific sequences and compared the results with interphase XY-fluorescent in situ hybridization (FISH). MC without signs of relapse was detected in 35% of samples using quantitative real-time PCR of Y-chromosome-specific sequences. The detected Y-DNA amounts were low compared to the amounts detected in 104 samples of 42 patients with leukemic relapse at the time of analysis (P < 0.0001). Quantitative real-time PCR of Y-chromosome-specific sequences detected therefore an increasing MC with high residual host DNA amounts approximately 143 days (mean) prior to the occurrence of relapse. By comparing the results of Y-chromosome PCR with the XY-FISH analysis we found concordant results in 73% in patients with myeloablative regimens. The XY-FISH could detect 12 relapses, whereas the Y-chromosome PCR detect 36 relapses by MC (P < 0.005). Residual host cells gradually decreased during the posttransplant period from a mean of 5.4 ng (first months) to 0.5 ng (above 5 years) without evidence of relapses. The probability of relapses was significantly higher in patients with increasing MC (100%) compared to 8% in patients with CC (P < 0.00001) associated with a significantly shorter overall survival in patients with increasing MC. The multivariate Cox model showed that chimerism analysis of Y-chromosome-specific sequences is an important risk factor for relapse (RR 17.0, P < 0.0001). We conclude that the use of real-time SNP or Y-PCR may be superior to the STR-PCR or interphase XY-FISH methods in detecting patients who are at high risk for relapse after transplant.

Adolescent↗
PubMedDate not supplied

Single-nucleotide polymorphism (SNP) analysis in the ABC half-transporter ABCG2 (MXR/BCRP/ABCP1).

Variations in the amino acid sequence of ABC transporters have been shown to impact substrate specificity. We identified two acquired mutations in ABCG2, the ABC half-transporter overexpressed in mitoxantrone-resistant cell lines. These mutations confer differences in substrate specificity and suggest that naturally occurring variants could also affect substrate specificity. To search for the existence of single nucleotide polymorphisms (SNPs) in ABCG2, we sequenced 90 ethnically diverse DNAs from the Single Nucleotide Polymorphism Discovery Resource representing the spectrum of human genotypes. We identified 3 noncoding SNPs in the untranslated regions, 3 nonsynonymous and 2 synonymous SNPs in the coding region and 7 SNPs in the intron sequences adjacent to the sixteen ABCG2 exons. Nonsynonymous SNPs at nucleotide 238 (V12M; exon 2) and nucleotide 625 (Q141K; exon 5) showed a greater frequency of heterozygosity (22.2% and 10%) than the SNP at 2062 (D620N; exon 16). Heterozygous changes at nucleotide 238 are in linkage disequilibrium with an SNP observed 36 bases downstream from the end of exon 2. No polymorphism at amino acid 482 was identified to correspond to the R to G or R to T mutations previously found in two drug resistant cell lines. Among 23 drug resistant sublines for which sequence at position 482 was determined, no additional mutations were found. Heterozygosity at amino acid 12 allowed us to identify overexpression of a single allele in a subset of drug resistant cell lines, a feature that could be exploited clinically in evaluating the significance of ABCG2 expression in malignancy. We conclude that ABCG2 is well conserved and that described amino acid polymorphisms seem unlikely to alter transporter stability or function.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2004

[Allele Frequency Analysis of Four Single Nucleotide Polymorphisms Locating in Promoter and 5'-Untranslated Regions of ABCAI Gene in Young Men - Survivors From Myocardial Infarction].

Analysis of allele distribution of four single nucleotide polymorphisms (C-17G, C69T, G-191C and 319insG) of promoter and 5'-untranslated regions of the ABCA1 gene was carried out in a sample of 171 men, who had survived myocardial infarction before 45 years, and in controls. Two-fold increase of T69 and C-191 allele frequencies were observed in Russian population in comparison to Dutch one. While comparing allele and genotype distributions of the polymorphisms in the samples under study no statistically significant differences were found, so as no influence of different alleles on lipid spectrum data was observed. Role of polymorphisms under study appears to be insignificant in formation of genetic susceptibility to myocardial infarction in young men.

5' Untranslated Regions↗
PubMed2004

[Association of single nucleotide polymorphism of vitamin D receptor gene start codon and the susceptibility to prostate cancer in the Han nationality in Hubei area].

OBJECTIVE: To investigate single nucleotide polymorphism of vitamin D receptor (VDR) gene start codon in the Han nationality in Hubei area and its relationship to the susceptibility to prostate cancer (PCa), and to study the possible mechanism for PCa. METHODS: The VDR genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 80 patients with PCa and 96 normal male controls from the Han nationality in Hubei area, using endonuclease Fok I. Direct sequencing was done in part of the PCR products. RESULTS: The frequency distribution of Fok I alleles in this cohort all followed the Hardy-Weinberg equilibrium. The distribution of genotypes and alleles had no significant difference between PCa patients and normal male controls( P > 0.05). CONCLUSION: The results indicated no significant relationship between Fok I polymorphism of VDR gene start codon and PCa in the Han nationality in Hubei area.

Aged↗
PubMed2001

Allele-specific binding of the ubiquitous transcription factor OCT-1 to the functional single nucleotide polymorphism (SNP) sites in the tumor necrosis factor-alpha gene (TNFA) promoter.

The tumor necrosis factor-alpha (TNFA) is characterized by several single nucleotide polymorphisms (SNPs) in its promoter region. Interestingly some of these SNPs appear to influence TNFA expression and susceptibility to various human diseases, but the molecular mechanisms by which such possibly functional SNPs modulate TNFA expression are poorly understood. In this study we show allele-specific binding of the ubiquitous transcription factor OCT-1 to the SNP sites at positions -863 and -857 in the promoter, which appear to affect TNFA expression: the protein was associated with variant allele possessing either -863A or -857T, but rarely with the common allele (-863C and -857C). The evidence presented here, therefore, suggests the possibility that OCT-1 could contribute to the modulation of TNFA expression by means of its allele-specific binding manner.

Alleles↗
PubMed2003

Room-temperature single-nucleotide polymorphism and multiallele DNA detection using fluorescent nanocrystals and microarrays.

We report two cDNA microarray-based applications of DNA-nanocrystal conjugates, single-nucleotide polymorphism (SNP) and multiallele detections, using a commercial scanner and two sets of nanocrystals with orthogonal emissions. We focus on SNP mutation detection in the human p53 tumor suppressor gene, which has been found to be mutated in more than 50% of the known human cancers. DNA-nanocrystal conjugates are able to detect both SNP and single-base deletion at room temperature within minutes, with true-to-false signal ratios above 10. We also demonstrate microarray-based multiallele detection, using hybridization of multicolor nanocrystals conjugated to two sequences specific for the hepatitis B and hepatitis C virus, two common viral pathogens that inflict more than 10% of the population in the developing countries worldwide. The simultaneous detection of multiple genetic markers with microarrays and DNA-nanocrystal conjugates has no precedent and suggests the possibility of detecting an even greater number of bacterial or viral pathogens simultaneously.

Alleles↗
PubMed2001

The single-nucleotide polymorphism lottery: how useful are a few common SNPs in identifying disease-associated alleles?

It has been proposed that using association analysis of single nucleotide polymorphism (SNP) markers in candidate genes may be more successful in identifying disease susceptibility genes for complex diseases. Finding all the SNPs within a candidate gene and genotyping a large case-control cohort is a resource-intensive process. As linkage disequilibrium extends across small regions of the genome, the expectation is that a few common anonymous SNPs will be sufficient to detect functional disease-associated alleles. The aim of this investigation was to compare the ability of a number of family- and population-based association methods to identify known susceptibility loci using the Genetic Analysis Workshop 12 simulated data set. As expected, case-control methods were more likely to detect association with individual SNPs but family-based haplotyping methods appeared better able to localize the position of functional polymorphism.

Adult↗
PubMed2006

No association of single nucleotide polymorphisms in the micro-opioid receptor subunit gene with idiopathic generalized epilepsy.

We have investigated the reported association (p = 0.019) between the A118G single nucleotide polymorphism (SNP) of the opioid receptor micro subunit gene (OPRM1) and idiopathic absence epilepsy (IAE). Five SNPs, including A118G, were investigated by association studies in a sample of 240 probands with idiopathic generalized epilepsy (IGE), including 110 with IAE, and 257 controls. No significant association was found for A118G with IGE or IAE. The difference between the two studies was in the control samples that had significantly different allele frequencies (p = 0.00005), suggesting that population stratification may explain the earlier significant association with IAE. In the current study, none of the other four SNPs was significantly associated with IGE or IAE. Our results provide no support for association of A118G with either IAE or IGE and also exclude association in our sample of a small-to-moderate gene effect with IGE from a large part of OPRM1.

Chromatography, High Pressure Liquid↗
PubMed2000

Twenty single nucleotide polymorphisms (SNPs) and their allelic frequencies in four genes that are responsible for familial long QT syndrome in the Japanese population.

We report here 20 single nucleotide polymorphisms (SNPs), including 10 novel ones, and their allelic frequencies detected in four genes that are known to be responsible for familial long QT syndrome in the Japanese population; 7 polymorphisms are in the KCNQ1 gene, 6 in the KCNH2 gene, 5 in the SCN5A gene, and 2 in the KCNE1 gene. These data will be of use for genetic association studies of acquired cardiac arrhythmias.

Alleles↗
PubMed2004

Allelic imbalance analysis by high-density single-nucleotide polymorphic allele (SNP) array with whole genome amplified DNA.

Besides their use in mRNA expression profiling, oligonucleotide microarrays have also been applied to single-nucleotide polymorphism (SNP) and loss of heterozygosity (LOH) or allelic imbalance studies. In this report, we evaluate the reliability of using whole genome amplified DNA for analysis with an oligonucleotide microarray containing 11 560 SNPs to detect allelic imbalance and chromosomal copy number abnormalities. Whole genome SNP analyses were performed with DNA extracted from osteosarcoma tissues and patient-matched blood. SNP calls were then generated by Affymetrix GeneChip DNA Analysis Software. In two osteosarcoma cases, using unamplified DNA, we identified 793 and 1070 SNP loci with allelic imbalance, respectively. In a parallel experiment with amplified DNA, 78% and 83% of these SNP loci with allelic imbalance was detected. The average false-positive rate is 13.8%. Furthermore, using the Affymetrix GeneChip Chromosome Copy Number Tool to analyze the SNP array data, we were able to detect identical chromosomal regions with gain or loss in both amplified and unamplified DNA at cytoband resolution.

Chromosomes, Human, Pair 6↗
PubMed2006

Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers.

BACKGROUND: The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1. METHODS: Genomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technologytrade mark was used to determine the genotype at the MDM2 SNP309 locus. RESULTS: The polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6%) and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G). Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T) individuals (72.7% vs. 75.6%, p = 1.00). Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80). CONCLUSION: We found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1.

Adolescent↗
PubMed2003

Haplotype tagging single nucleotide polymorphisms and association studies.

OBJECTIVES: Discrete blocks of low haplotype diversity exist within the human genome. The non-redundant subset of 'haplotype tagging' single nucleotide polymorphisms (htSNPs) in such blocks can distinguish a majority of the haplotypes. Several approaches have been proposed to determine htSNPs, ranging from visual inspection to formal analytic procedures. Optimal htSNPs can be estimated using a small subgroup of an association study population that have been genotyped for a dense SNP map, and it is just these htSNPs that are genotyped in the remainder of the samples. We investigated by simulation how the size of the subsample affects the power of association studies, and what type of subjects it should include. METHODS: We used the program tagSNPs [Stram et al., Hum Hered 2003;55:27-36], which selects htSNPs to minimize the uncertainty in predicting common haplotypes for individuals with unphased genotype data. RESULTS: On average, 27% of the SNPs were designated as htSNPs. Genotyping as few as 25 unphased individuals to select the htSNPs did not appear to reduce the power of an association study, as compared with using all SNPs. For the disease models considered, selecting htSNPs based on cases, controls, or a mixture of both gave similar results. CONCLUSIONS: These results suggest that the genotyping effort in an association study can be substantially reduced with little loss of power by identifying htSNPs in a small subsample of individuals.

Chromosome Mapping↗