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PubMed2001

Regions of low single-nucleotide polymorphism incidence in human and orangutan xq: deserts and recent coalescences.

While scanning for single-nucleotide polymorphisms (SNPs) in the human Xq25-q28 region of CEPH families, we found six long "deserts" of low SNP incidence representing 28% of the investigated genome. One was 1.66 Mb in length. To determine whether these SNP deserts were due to reduced input of mutations or to recent coalescent events such as bottlenecks or selective sweeps, comparative sequence was determined from a female orangutan. The mean divergence was 2.9% and was not reduced in deserts compared with nondesert regions. Thus, the best explanation for the SNP deserts is recent coalescent events in humans. These events are the cause of substantial variation in human noncoding SNP incidence. In addition, the mutational spectrum in humans and orangutans was estimated as 63% AG (and CT), 17% AC (and GT), 8% CG, 4% AT, and 8% insertion/deletions. The average lifetime of a SNP destined to become fixed for a new allele between these species was estimated as 284,000 years.

Alleles↗

PubMed2001

Single nucleotide polymorphism identification in candidate gene systems of obesity.

We have constructed a large panel of single nucleotide polymorphisms (SNP) identified in 68 candidate genes for obesity. Our panel combines novel SNP identification methods based on EST data, with public SNP data from largescale genomic sequencing, to produce a total of 218 SNPs in the coding regions of obesity candidate genes, 178 SNPs in untranslated regions, and over 1000 intronic SNPs. These include new non-conservative amino acid changes in thyroid receptor beta, esterase D, acid phosphatase 1. Our data show evidence of negative selection among these polymorphisms implying functional impacts of the non-conservative mutations. Comparison of overlap between SNPs identified independently from EST data vs genomic sequencing indicate that together they may constitute about one half of the actual total number of amino acid polymorphisms in these genes that are common in the human population (defined here as a population allele frequency above 5%). We have analyzed our polymorphism panel to construct a database of detailed information about their location in the gene structure and effect on protein coding, available on the web at http://www.bioinformat ics.ucla.edu/snp/obesity. We believe this panel can serve as a valuable new resource for genetic and pharmacogenomic studies of the causes of obesity.

Databases, Genetic↗

PubMed2001

A rapid screening method for a single nucleotide polymorphism (SNP) in the human MOR gene.

AIMS: Genetic association studies have suggested that the single nucleotide polymorphism (SNP) at position 118 of the human mu-opioid receptor (MOR) gene could be a potential risk factor for drug treatment variability in patients. Therefore, we wanted to develop a fast and reliable detection method for this SNP which is applicable in a clinical setting. METHODS: To detect the polymorphism at position A118-->G in the human MOR gene we used the fluorescence resonance energy transfer (FRET)-PCR technique with subsequent melting curve analysis. RESULTS: The polymorphism at position A118-->G in the human MOR gene could be clearly discriminated with melting peak temperatures of 69.8 degrees C and 63.8 degrees C, corresponding to the wild type and mutated MOR allele, respectively. The results from FRET-PCR were validated by sequencing and restriction-fragment length polymorphism (RFLP). Screening of blood samples from 100 subjects showed an allelic distribution for the human MOR alleles of 79% (homozygous wild type), 20% (heterozygous) and 0.9% (homozygous mutated). CONCLUSIONS: The FRET-PCR protocol for detection of the human MOR gene polymorphism at position 118 offers a rapid and reliable method which could be used for population screening of this and other genes.

DNA↗

PubMed2001

Flow cytometric platform for high-throughput single nucleotide polymorphism analysis.

We have developed a rapid, cost-effective, high-throughput readout for single nucleotide polymorphism (SNP) genotyping using flow cytometric analysis performed on a Luminex 100 flow cytometer. This robust technique employs a PCR-derived target DNA containing the SNP, a synthetic SNP-complementary ZipCode-bearing capture probe, a fluorescent reporter molecule, and a thermophilic DNA polymerase. An array of fluorescent microspheres, covalently coupled with complementary ZipCode sequences (cZipCodes), was hybridized to the reaction products and sequestered them for flow cytometric analysis. The single base chain extension (SBCE) reaction was used to assay 20 multiplexed SNPs for 633 patients in 96-well format. Comparison of the microsphere-based SBCE assay results to gel-based oligonucleotide ligation assay (OLA) results showed 99.3% agreement in genotype assignments. Substitution of direct-labeled R6G dideoxynucleotide with indirect-labeled phycoerythrin dideoxynucleotide enhanced signal five- to tenfold while maintaining low noise levels. A new assay based on allele-specific primer extension (ASPE) was validated on a set of 15 multiplexed SNPs for 96 patients. ASPE offers both the advantage of streamlining the SNP analysis protocol and the ability to perform multiplex SNP analysis on any mixture of allelic variants.

Flow Cytometry↗

PubMed2001

[Study on distribution of single nucleotide polymorphism in 5'-regulatory region of beta(2)-adrenoceptor gene in hypertensives].

OBJECTIVE: To detect single nucleotide polymorphisms (SNP) existing in 5'-regulatory region of beta(2)-adrenoceptor (beta(2)-AR) gene and to investigate their associations with hypertension. METHODS: beta(2)-AR gene was sequenced by fluorescent labeling automatic sequencing method in unrelated Chinese Han population distributed in Dabie Mountain in Anhui Province. Genotypes of the SNP were typed by PCR-RFLP method. RESULTS: Two SNP of 1.3 kb long were identified at position 1023 and 654 respectively. They were both G-->A substitution. The frequency of genotype of the two SNP complied well with the Hardy-Weinberg equilibrium. The distribution of the SNP genotype AA, GA and GG at position 1023 in the severe hypertension group was significantly different from that in normal group (chi(2) = 9.53, df = 2, P < 0.01), AA frequency is significantly higher in the severe hypertension group than in the normal group (chi(2) = 9.21, df = 1, P < 0.01). CONCLUSION: The SNP at locus 1023 of human beta(2)-AR gene is associated with severe hypertension in Chinese Han population.

Aged↗

PubMed2004

Comparative high-resolution analysis of linkage disequilibrium and tag single nucleotide polymorphisms between populations in the vitamin D receptor gene.

A genome-wide map of single nucleotide polymorphisms (SNP) and a pattern of linkage disequilibrium (LD) between their alleles are being established in three main ethnic groups. An important question is the applicability of such maps to different populations within a main ethnic group. Therefore, we have developed high-resolution SNP, haplotype and LD maps of vitamin D receptor gene region in large samples from five populations. Comparative analysis reveals that the LD patterns are identical in all four European populations tested with two small regions of 1.3 and 5.7 kb at which LD is disrupted completely resulting in three block-like regions over which there is significant and extensive LD. In an African population the pattern is similar, but two additional LD-breaking spots are also apparent. This LD pattern suggests combined action of recombination hotspots and founder effects, but cannot be explained by random recombination and genetic drift alone. Direct comparison indicates that the tag SNPs selected in one European population effectively predict the non-tag SNPs in the other Europeans, but not in the Gambians, for this region.

Chromosomes, Human, Pair 12↗

PubMed2004

[Association of APOA5 gene single nucleotide polymorphism with levels of lipids and coronary heart disease in Chinese].

OBJECTIVE: To investigate the single nucleotide polymorphism 4 (SNP4) of the apolipoprotein A5 (APOA5) gene possible association with coronary heart disease(CHD) and its distribution of in Chinese Han population. METHODS: APOA5 SNP4 genotyping was performed using polymerase chain reaction and Hae III restriction fragment length polymorphism analysis. RESULTS: APOA5 allelic frequencies of T, C were 0.435, 0.565 and 0.374, 0.626 in CHD group and control group, respectively. There is significant difference in allele and genotype frequencies between CHD group and control group (P<0.05). The levels of plasma high density lipoprotein in CHD patients with CC genotype were higher than those in CHD patients with other genotypes (P<0.01). The frequencies of T allele and C allele in Chinese was significantly different from those in Caucasians (0.374 vs 0.663, 0.626 vs 0.337, P<0.01). The C allele was much more common in Chinese population. CONCLUSION: The association is found between the Hae III polymorphism and CHD, There is a significant correlation between the CC genotype of the APOA5 and the levels of plasma high density lipoprotein-cholosteal in the CHD group.

Adult↗

PubMed2005

Microsatellites versus single-nucleotide polymorphisms in linkage analysis for quantitative and qualitative measures.

BACKGROUND: Genetic maps based on single-nucleotide polymorphisms (SNP) are increasingly being used as an alternative to microsatellite maps. This study compares linkage results for both types of maps for a neurophysiology phenotype and for an alcohol dependence phenotype. Our analysis used two SNP maps on the Illumina and Affymetrix platforms. We also considered the effect of high linkage disequilibrium (LD) in regions near the linkage peaks by analysing a "sparse" SNP map obtained by dropping some markers in high LD with other markers in those regions. RESULTS: The neurophysiology phenotype at the main linkage peak near 130 MB gave LOD scores of 2.76, 2.53, 3.22, and 2.68 for the microsatellite, Affymetrix, Illumina, and Illumina-sparse maps, respectively. The alcohol dependence phenotype at the main linkage peak near 101 MB gave LOD scores of 3.09, 3.69, 4.08, and 4.11 for the microsatellite, Affymetrix, Illumina, and Illumina-sparse maps, respectively. CONCLUSION: The linkage results were stronger overall for SNPs than for microsatellites for both phenotypes. However, LOD scores may be artificially elevated in regions of high LD. Our analysis indicates that appropriately thinning a SNP map in regions of high LD should give more accurate LOD scores. These results suggest that SNPs can be an efficient substitute for microsatellites for linkage analysis of both quantitative and qualitative phenotypes.

Alcoholism↗

PubMedDate not supplied

Homozygosity in the single nucleotide polymorphism Ser128Arg in the E-selectin gene associated with recurrent venous thromboembolism.

BACKGROUND: The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin gene is overrepresented in certain patient populations with atherosclerosis or restenosis. As this SNP enhances tissue factor-triggered coagulation in humans during systemic inflammation, we hypothesized that it may also predispose for the development of recurrent venous thromboembolism (VTE). METHODS: A total of 585 patients were prospectively observed after first VTE for recurrent, objectively documented, symptomatic VTE. Patients with secondary VTE, homozygous factor V Leiden, natural inhibitor deficiencies, lupus anticoagulant, or long-term anticoagulation therapy were excluded. The S128R SNP was genotyped by mutagenically separated polymerase chain reaction. RESULTS: A total of 102 patients (17%) were heterozygous, and 11 were homozygous (2%) for the Ser128Arg mutation. Ninety patients (15%) had recurrent VTE during follow-up. Homozygosity for the Ser128Arg SNP increased the cumulative likelihood, particularly for early recurrent VTE (log rank test, P<.05) and was an independent predictor of recurrent VTE (hazard ratio [HR], 4.1; 95% confidence interval [CI], 1.5-11.4) in a multivariate Cox regression model. In contrast, heterozygosity for the polymorphism was associated with an unaltered HR (HR, 1.1; 95% CI, 0.6-1.9) for recurrent VTE. CONCLUSIONS: Homozygosity for the S128R E-selectin allele appears to increase the risk for recurrent VTE several fold. If these findings are confirmed, this may represent a novel risk factor for recurrent VTE. These results also expand our knowledge on the association of this SNP with thrombotic disorders.

Adult↗

PubMed2006

Concordance between the deduced acetylation status generated by high-speed: real-time PCR based NAT2 genotyping of seven single nucleotide polymorphisms and human NAT2 phenotypes determined by a caffeine assay.

BACKGROUND: The utility of typing single nucleotide polymorphisms (SNPs) for the determination of the N-acetyltransferase 2 (NAT2) acetylation status is a matter of debate. AIMS OF THE STUDY: Evaluation of the concordance between deduced genotype results of seven human NAT2 SNPs generated by Real-time PCR analysis and human NAT2 phenotypes. METHODS: NAT2 phenotypes of 38 Caucasian workers were determined using a suitable caffeine test method. Genomic DNA aliquots were used for the determination of seven human NAT2-specific SNPs (G191A, C282T, T341C, C481T, G590A, A803G, G857A). RESULTS AND CONCLUSIONS: Phenotypic results based on the molar ratio of 5-acetylamino-6-formylamino-3-methyluracil (AFMU)/(AFMU+1-methlyuric acid (1U)+1-methylxanthine (1X)) calculated from excreted caffeine metabolite levels in urine samples with 0.3 as a cut-off point between slow (<0.3) and rapid acetylators (>or=0.3). Twenty-seven samples belonged to the slow (mean 0.13; range: 0.03-0.25), 11 to the rapid (mean: 0.41; range: 0.34-0.48) acetylators. LightCycler analyses revealed 11 different NAT2 variant combinations, whereby *5B/*5B and *5B/*6A or *5A/*6C (each 21%), were the most frequent. The deduced acetylation status of the seven NAT2 SNPs matched perfectly with the 38 results determined by phenotyping. This study showed a 100% concordance between NAT2 phenotypes and the deduced NAT2 genotypes and the suitability of the high-speed NAT2-specific LightCycler analysis in a Caucasian population.

Acetylation↗

PubMedDate not supplied

Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction.

The FSH receptor shows three single nucleotide polymorphisms (SNPs), one in the promoter and two in exon 10. In addition, the FSH receptor mRNA undergoes extensive alternative splicing. While no physiological role for the SNP in the promoter and for alternative spliced isoforms has been demonstrated so far, the SNPs in exon 10 result in four discrete allelic variants characterized by the amino acid combinations Thr307-Asn680, Ala307-Ser680, Ala307-Asn680 and Thr307-Ser680. Several studies have demonstrated that the first two allelic variants are very frequent (approximately 60 and 40% respectively) in the Caucasian population. The rarer Ala307-Asn680 and Thr307-Ser680 variants are much less frequent (<5%) in the Chinese. In males the FSH receptor variants are not related to testicular volume, serum FSH or serum inhibin B levels. The two most common receptor variants transiently transfected in COS-7 cells displayed similar functional characteristics. Frequency distribution of the two polymorphisms in normal women and patients with polycystic ovarian syndrome or premature ovarian failure is still under investigation. The homozygous Ala307-Ser680 variant seems to be associated with significantly higher basal serum FSH levels and with a higher amount of FSH required for ovarian stimulation in women undergoing assisted reproduction. This suggests that the FSH receptor genotype can influence the ovarian response to FSH stimulation. The presence of SNPs in the FSH receptor gene capable of modifying FSH action paves the way for future patient-tailored, genotype-based hormone therapies.

Alleles↗

PubMed2002

Two new single-nucleotide polymorphisms in the COL1A1 upstream regulatory region and their relationship to bone mineral density.

Single-nucleotide polymorphisms (SNPs) in regulatory regions of candidate genes may determine variability in bone mineral density (BMD) because they may be responsible for differences in levels of a gene product in response to external signals. Under this hypothesis, we scanned an 800-base pair (bp) region within the COL1A1 promoter, known to harbor cis elements important for in vivo expression, and we found two new polymorphisms: -1663indelT and -1997 G/T. The G to T transversion at -1997 was associated with lumbar spine BMD (p = 0.015) when tested in a cohort of 256 postmenopausal women after adjusting by age, body weight, and years since menopause; a lower degree of association was detected also for femoral neck BMD in a subgroup of 146 women in univariate analysis and after adjusting by age (p = 0.044). The polymorphism -1663indelT, which corresponds to a deletion of a T in a tract of eight T residues (-1670 to -1663), did not show significant association with BMD. Interestingly, -1663indelT is in strong linkage disequilibrium (LD) with the previously described Sp1 polymorphism of intron 1, which in this study did not show association with BMD either. Significant interaction between -1997 G/T and -1663indelT (p = 0.019), and between -1997 G/T and Sp1 (p = 0.045) was observed also. Individuals heterozygous for the three polymorphisms showed the highest mean BMD value. Gel retardation assays showed that oligonucleotides containing either the -1663 or the -1997 polymorphic sites specifically bind primary osteoblast nuclear proteins. We named these binding sites as PCOL1 and PCOL2, respectively. In summary, this study describes two new SNPs in the COL1A1 promoter, which may affect bone mass determination.

Alleles↗

PubMed2006

Microsatellites versus Single-Nucleotide Polymorphisms in confidence interval estimation of disease loci.

With cost-effective high-throughput Single Nucleotide Polymorphism (SNP) arrays now becoming widely available, it is highly anticipated that SNPs will soon become the choice of markers in whole genome screens. This optimism raises a great deal of interest in assessing whether dense SNP maps offer at least as much information as their microsatellite (MS) counterparts. Factors considered to date include information content, strength of linkage signals, and effect of linkage disequilibrium. In the current report, we focus on investigating the relative merits of SNPs vs. MS markers for disease gene localization. For our comparisons, we consider three novel confidence interval estimation procedures based on confidence set inference (CSI) using affected sib-pair data. Two of these procedures are multipoint in nature, enabling them to capitalize on dense SNPs with limited heterozygosity. The other procedure makes use of markers one at a time (two-point), but is much more computationally efficient. In addition to marker type, we also assess the effects of a number of other factors, including map density and marker heterozygosity, on disease gene localization through an extensive simulation study. Our results clearly show that confidence intervals derived based on the CSI multipoint procedures can place the trait locus in much shorter chromosomal segments using densely saturated SNP maps as opposed to using sparse MS maps. Finally, it is interesting (although not surprising) to note that, should one wish to perform a quick preliminary genome screening, then the two-point CSI procedure would be a preferred, computationally cost-effective choice.

Chromosome Mapping↗

PubMed2002

[Study on single nucleotide polymorphism of TIGR gene in primary open-angle glaucoma patients].

OBJECTIVE: To detect the single nucleotide polymorphism (SNP) of trabecular meshwork-induced glucocorticoid response protein (TIGR) gene and to investigate the association between SNP and primary open-angle glaucoma (POAG) in Chinese Han population. METHODS: High throughput conformation sensitive gel electrophoresis (HTCSGE) and fluorescent labeling automated sequencing method were used to screen and identify the SNPs of TIGR in 82 unrelated patients with POAG. Restriction endonuclease analysis was used to detect the SNPs of TIGR in 150 sex-and age-matched unrelated control subjects without POAG. The frequencies of genotypes and alleles of each SNP between the two groups were compared by chi-square test. RESULTS: A total of six SNPs were identified in TIGR gene with a length of 2172 bp, including all coding regions and part of promoter, introns and 3'UTR region: 1-83(G --> A), G12R, R46X, R76K, IVS2 + 35(A --> G), and T353I. Significant differences were found in frequencies of the genotype TC and the allele T of T353I between POAG patients and control subjects. The frequency of heterozygote TC was 12.20% in POAG patients, significantly higher than that in control subjects (3.33%, kappa(2) = 6.885, P = 0.009, OR = 4.028, OR95% CI = 1.327 approximately 12.223). The frequency of the allele T was 6.10% in POAG patients, significantly higher than that in control subjects (1.67%, kappa(2) = 6.655, P = 0.010). No significant difference was found between the two groups in frequencies of genotypes and alleles of the other SNPs. CONCLUSION: The T353I polymorphism of TIGR gene is associated with POAG in Chinese Han population.

Aged↗

PubMed2003

Prospective analysis of single nucleotide polymorphisms of the transforming growth factor beta-1 gene in Peyronie's disease.

PURPOSE: The detection of increased expression of transforming growth factor beta-1 (TGF-beta1) in Peyronie's disease plaques and the possibility of initiating a Peyronie's disease-like condition by intratunical injection of a synthetic heptopeptide with TGF-beta-like activity in an animal model has provided evidence for the central role of this cytokine in the pathogenesis of this entity. Recently 2 defined single nucleotide polymorphisms in the coding region of the TGF-beta1 gene have been described that are associated with different levels of TGF-beta1 production. Based on these data we prospectively investigated the genetic association of distinct TGF-beta1 genotypes with Peyronie's disease. MATERIALS AND METHODS: DNA samples from 111 consecutive patients with idiopathic Peyronie's disease and 100 controls were genotyped for the 2 defined dimorphic single nucleotide polymorphisms T869C and G915C in the coding region of the TGF-beta1 gene using allele specific polymerase chain reaction. RESULTS: We found an increased frequency of the homozygous genotype of the single nucleotide polymorphism G915C in patients with Peyronie's disease compared with healthy controls (89.2% versus 79%, p = 0.04). However, there were no significant differences in allele frequencies of the single nucleotide polymorphism T869C. CONCLUSIONS: Experimental data from other investigators have shown that TGF-beta1 has an important role in the etiopathology of Peyronie's disease. Our results indicate that the homozygous wild type of the G915C single nucleotide polymorphism in the coding region of the TGF-beta1 gene, which was recently associated with elevated TGF-beta1 production and pulmonary fibrosis, may influence the predisposition to Peyronie's disease. However, it does not represent a major genetic risk factor.

Adult↗

PubMed2004

[Single nucleotide polymorphisms of the myocilin gene in primary open-angle glaucoma patients].

OBJECTIVE: To detect single nucleotide polymorphisms (SNPs) of the myocilin (MYOC) gene and to investigate their associations with primary open-angle glaucoma (POAG). METHODS: One hundred and fifty-seven sporadic patients with POAG and 155 unrelated control subjects without POAG were recruited from staff and visitors to the Prince of Wales Hospital between 1998 and 2000. All study subjects are ethnic Chinese living in Hong Kong. The two populations were matched in frequencies of gender and age. The SNPs of the MYOC gene in POAG patients and control subjects were screened and identified by high throughout conformation sensitive gel electrophoresis and fluorescent labeling automated sequencing. The genotype frequencies of each SNP in the two groups were compared by the Chi2 test or Fisher's exact 2-tailed test. RESULTS: A total of seventeen SNPs were identified from 2172 bp long of the MYOC gene, including all 3 exons and adjacent non-coding regions. The identified SNPs were 1-83G --> A, G12R, P16L, A17S, R46X, R76K, R91X, T123T, D208E, L215P, 730+35A --> G, A260A, I288I, E300K, T353I, Y471C and 1515+73G --> C, respectively. Of these, R91X, E300K and Y471C were found only in POAG patients. A significant difference between POAG patients and control subjects was found in the genotype frequencies of 1515+73G --> C. The frequency of the heterozygote (CG) was 0.6% in POAG patients, significantly less than the 4.5% in control subjects (Fisher's exact 2-tailed test, P=0.036, OR=0.136, 95%CI=0.022-0.828). No significant difference was found between the two populations in genotype frequencies of all other SNPs. CONCLUSION: The polymorphisms of the MYOC gene may be related to POAG.

Adult↗

PubMed2005

Linkage and association analyses of microsatellites and single-nucleotide polymorphisms in nuclear families.

Several simulation studies have suggested that a high-density single-nucleotide polymorphisms (SNPs) marker set may be as useful as a traditional microsatellites (MS) marker set in performing whole-genome linkage analysis. However, very few studies have directly tested the SNPs-based genome-wide scan. In the present study, we compared the linkage results from the SNPs-based scan with a map density of 3-cM spacing with those from the MS scan using a 10-cM marker set among 300 nuclear families each from the Aipotu (AI), Danacaa (DA), and Karangar (KA) populations from the simulated Genetic Analysis Workshop 14 Problem 2 data. We found that information contents obtained from the SNPs scan were somewhat lower than those from the MS scan. However, the linkage results obtained from the two scans showed a high degree of similarity. Both scans identified a similar number of chromosomal regions attaining nominal significance (p < 0.05). Specifically, both scans detected confirmed evidence for linkage (NPL >or= 4.07, p = 2 x 10(-5)) to chromosome 1 in the AI families, chromosomes 1 and 3 in the DA families, and chromosomes 3, 5, and 9 in the KA families. An additional confirmed linkage to chromosome 5 in the AI families was detected only by the MS scan. We also observed slightly wider 1-LOD intervals for more of the SNP peaks than for the MS peaks, which is likely due to lower information contents for the SNPs. Subsequent fine-mapping association analysis further identified 2 to 3 markers significantly associated with disease status in each population; B03T3056, B03T3058, and B05T4139 in the AI population, B03T3056 and B03T3058 in the KA population, and B03T3056, B03T3057, and B03T3058 in the DA population. Among the four markers, three were chosen based on results obtained from the two scans, but one was solely from the SNP scan. In summary, our finding suggests that the SNP-based genome scan has the potential to be as powerful as the traditional MS-based scan and offers good identification of peak location for further fine-mapped association analysis.

Alleles↗

PubMed2003

A 3.9-centimorgan-resolution human single-nucleotide polymorphism linkage map and screening set.

Recent advances in technologies for high-throughout single-nucleotide polymorphism (SNP)-based genotyping have improved efficiency and cost so that it is now becoming reasonable to consider the use of SNPs for genomewide linkage analysis. However, a suitable screening set of SNPs and a corresponding linkage map have yet to be described. The SNP maps described here fill this void and provide a resource for fast genome scanning for disease genes. We have evaluated 6,297 SNPs in a diversity panel composed of European Americans, African Americans, and Asians. The markers were assessed for assay robustness, suitable allele frequencies, and informativeness of multi-SNP clusters. Individuals from 56 Centre d'Etude du Polymorphisme Humain pedigrees, with >770 potentially informative meioses altogether, were genotyped with a subset of 2,988 SNPs, for map construction. Extensive genotyping-error analysis was performed, and the resulting SNP linkage map has an average map resolution of 3.9 cM, with map positions containing either a single SNP or several tightly linked SNPs. The order of markers on this map compares favorably with several other linkage and physical maps. We compared map distances between the SNP linkage map and the interpolated SNP linkage map constructed by the deCode Genetics group. We also evaluated cM/Mb distance ratios in females and males, along each chromosome, showing broadly defined regions of increased and decreased rates of recombination. Evaluations indicate that this SNP screening set is more informative than the Marshfield Clinic's commonly used microsatellite-based screening set.

Alleles↗