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At least 1,135 records · Page 63Linked to original sources
PubMed2005

SYNGR1 is associated with schizophrenia and bipolar disorder in southern India.

Chromosome 22q11-13 is one of the most consistent linkage regions for schizophrenia (SCZ) and bipolar disorder (BPAD). The SYNGR1 gene, which is associated with presynaptic vesicles in neuronal cells, is located on 22q13.1. We have previously identified a novel nonsense mutation in the SYNGR1 gene in a SCZ pedigree. In the present study, a detailed analysis of this gene was performed in a case-control cohort (198 BPAD, 193 SCZ and 107 controls from southern India) to test for association with SCZ and BPAD. Sequence analysis of all exonic and flanking intronic regions of the SYNGR1 gene in 198 BPAD and 193 SCZ cases revealed a novel mutation Lsy99Glu (in one BPAD patient) and two other novel common polymorphisms [synonymous single nucleotide polymorphism (SNP--Ser97Ser) and an Asn ins/del] in the SYNGR1 gene. We also validated 9 out of 14 dbSNPs in our population. Case-control analysis revealed allelic (P = 0.028-0.00007) association of five polymorphisms with SCZ and/or BPAD cases. Further, 3-SNP (with LD block 1 SNPs) and 2-SNP (with LD block 2 SNPs) haplotype analyses did not show any association with either SCZ or BPAD. Our results support SYNGR1 as a probable susceptibility gene for SCZ and BPAD. Also, the observed association of SYNGR1 with both SCZ and BPAD suggests the likely involvement of a common pathway in the etiology of these disorders.

Adolescent↗
PubMed2001

High-throughput identification, database storage and analysis of SNPs in EST sequences.

Single nucleotide polymorphisms (SNPs) are the most frequent form of DNA variation and disease-causing mutations in many genes. Due to their abundance and slow mutation rate within generations, they are thought to be the next generation of genetic markers that can be used in a myriad of important biological, genetic, pharmacological, and medical applications. There are several strategies both experimental, and in-silico for SNP discovery and mapping. Experimental SNP discovery consists of a number of labourious steps that make this process complex and expensive. In-silico discovery has been proposed as an alternative discovery method that makes use and takes advantage of large data sets with potential SNP information that have been generated with other purposes and have not been used as a SNP information source yet. However, in order to successfully apply the in-silico method to large data sets, the following challenges need to be addressed: First it is necessary to build an integrated SNP pipeline that handles data processing steps smoothly from the beginning (collecting sequence information) to end (SNPs in the database). Also, SNP detection tool parameters have to be optimized to satisfy specific goals of the project. Finally, SNP data could not be fully used until the in-silico method is validated experimentally. In this paper we present a design and implementation of an in-silico SNP detection software pipeline that exploits the existence of large EST (expressed sequence tag) data sets and effectively addresses the above challenges. First, the pipeline allows for smooth data transition between its different components by implementing data interfaces that translate the data formats of the different tools in the different stages. Second, we optimized PolyBayes parameters for SNP detection in maize EST. Finally, we implemented a user interface that along with the database structure created allows the scientist to perform preliminary analysis of the data and to perform basic statistics on the SNP data prior to experimental validation. The pipeline works with two different types of sequence assemblers (PHRAP (http://www.phrap.org/) and CAT from DoubleTwist (http://www.doubletwist.com/). It uses a Bayesian engine for SNP detection (PolyBayes), selects relevant polymorphism information which is then uploaded into a database. We detected 2439 SNPs and 822 insertion deletions (INDELs) with a PolyBayes probability higher than 0.99 on the public set of 68,000 maize ESTs. The user interface allowed us analyzing the polymorphism information right after discovery in several ways that allowed us to gain insight into the distribution and significance of the newly acquired data.

Animals↗
PubMed2003

Large-scale identification and analysis of genome-wide single-nucleotide polymorphisms for mapping in Arabidopsis thaliana.

Genetic markers such as single nucleotide polymorphisms (SNPs) are essential tools for positional cloning, association, or quantitative trait locus mapping and the determination of genetic relationships between individuals. We identified and characterized a genome-wide set of SNP markers by generating 10,706 expressed sequence tags (ESTs) from cDNA libraries derived from 6 different accessions, and by analysis of 606 sequence tagged sites (STS) from up to 12 accessions of the model flowering plant Arabidopsis thaliana. The cDNA libraries for EST sequencing were made from individuals that were stressed by various means to enrich for transcripts from genes expressed under such conditions. SNPs discovered in these sequences may be useful markers for mapping genes involved in interactions with the biotic and abiotic environment. The STS loci are distributed randomly over the genome. By comparison with the Col-0 genome sequence, we identified a total of 8051 SNPs and 637 insertion/deletion polymorphisms (InDel). Analysis of STS-derived SNPs shows that most SNPs are rare, but that it is possible to identify intermediate frequency framework markers that can be used for genetic mapping in many different combinations of accessions. A substantial proportion of SNPs located in ORFs caused a change of the encoded amino acid. A comparison of the density of our SNP markers among accessions in both the EST and STS datasets, revealed that Cvi-0 is the most divergent accession from Col-0 among the 12 accessions studied. All of these markers are freely available via the internet.

Arabidopsis↗
PubMed2005

Mutational and expression analysis of tbnat and its response to isoniazid.

A gene (nat) encoding arylamine N-acetyltransferase (NAT) has been found in Mycobacterium tuberculosis. The gene is expressed and the enzyme is active in growing M. tuberculosis cells. N-Acetyltransferase acetylates and inactivates isoniazid (INH), which is a front-line drug used in tuberculosis (TB) therapy. In this study, it was shown that a previously reported G619A single nucleotide polymorphism (SNP) was conserved in two M. tuberculosis strain families found in the Western Cape Province of South Africa (strain families 3 and 28). Further sequence analysis of isolates in strain family 3 identified a new T529C SNP in NAT resulting in a histidine instead of a tyrosine at position 177. This SNP was found only in isolates from strain family 3, and this mutation affects the highly conserved tyrosine residue close to the active site. Using real-time PCR, the expression of M. tuberculosis nat (tbnat) was determined over a 28 day growth cycle of the M. tuberculosis reference strain (H37Rv). The expression of tbnat occurs early in growth and reaches maximum levels at mid-exponential phase. The exposure of INH-susceptible isolates to low levels of INH resulted in an increase of tbnat expression (reference strain H37Rv, which is wild-type for tbnat, and isolate 1430, containing both SNPs). An INH-resistant isolate (816) exposed to INH showed no change in tbnat expression. The increased expression in the susceptible isolates suggests that INH affects tbnat expression. tbnat may contribute to INH susceptibility, but in combination with other factors.

Antitubercular Agents↗
PubMed2006

Clustering of insulin resistance with vascular dysfunction and low-grade inflammation in type 2 diabetes.

Vascular dysfunction, low-grade inflammation, insulin resistance, and impaired fibrinolysis have each been reported to be present in type 2 diabetes, but their relationships, and the role of obesity, have not been investigated. We measured insulin sensitivity (euglycemic clamp), forearm blood flow responses to graded local acetylcholine (Ach) and sodium nitroprusside (SNP) infusions, plasma concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, von Willebrand factor (vWF), plasminogen activator inhibitor (PAI)-1, tissue plasminogen activator (tPA), and high-sensitivity C-reactive protein (hs-CRP) in 81 diabetic patients. When patients were stratified by insulin resistance, more severe insulin resistance was associated (P < 0.05) with overweight, central fat distribution, hypertension, and dyslipidemia (with similar sex distribution, age, fasting plasma glucose, and HbA1c). With regard to vascular function, both endothelium-dependent (Ach) (-22, -40, and -52%; P < 0.0001) and -independent (SNP) (-3, -7, and -27%; P < 0.02) vasodilatation were progressively reduced across insulin resistance tertiles. In multivariate analysis, inflammatory markers (IL-6, hs-CRP, and TNF-alpha) were independently associated with insulin resistance and fasting glycemia, fibrinolytic markers PAI-1 and tPA with insulin resistance and central fat distribution, and vascular indexes (vWF, Ach, and SNP vasodilation) with insulin resistance and obesity or cytokines (TNF-alpha or IL-6). In type 2 diabetes, insulin resistance is associated with vascular dysfunction/damage, impaired fibrinolysis, and low-grade inflammation independently of obesity and poor glycemic control.

Acetylcholine↗
PubMed2005

A genome scan for parent-of-origin linkage effects in alcoholism.

BACKGROUND: Alcoholism is a complex disease in which genomic imprinting may play an important role in its susceptibility. OBJECTIVE: To conduct a genome-wide search for loci that may have strong parent-of-origin linkage effects in alcoholism; to compare the linkage results between the microsatellites and the two single-nucleotide polymorphism (SNP) platforms. METHODS: Nonparametric linkage analyses were performed using ALLEGRO with the three sets of markers provided by the Genetic Analysis Workshop 14 for the Collaborative Study on the Genetics of Alcoholism Problem 1 data. Both sex-averaged and sex-specific genetic maps were used. We also provided a valid statistical test to determine whether the parental allele sharing differed significantly. RESULTS: Significant maternal linkage effects (paternal imprinting) were observed on chromosome 12 using either the microsatellite markers or the two SNP panels. The two SNP sets did not improve the linkage signals compared to the results from the microsatellite markers on chromosome 12. Possible paternal linkage effects (maternal imprinting) on chromosome 7 and maternal linkage effects (paternal imprinting) on chromosome 10 were found using the two SNP panels. CONCLUSION: For diseases which may have parent-of-origin effects, linkage analysis looking at parental sharing separately may reduce locus heterogeneity and increase the ability to identify that which can not be identified with usual linkage analysis.

Alcoholism↗
PubMed2004

Maximum-likelihood estimation of haplotype frequencies in nuclear families.

The importance of haplotype analysis in the context of association fine mapping of disease genes has grown steadily over the last years. Since experimental methods to determine haplotypes on a large scale are not available, phase has to be inferred statistically. For individual genotype data, several reconstruction techniques and many implementations of the expectation-maximization (EM) algorithm for haplotype frequency estimation exist. Recent research work has shown that incorporating available genotype information of related individuals largely increases the precision of haplotype frequency estimates. We, therefore, implemented a highly flexible program written in C, called FAMHAP, which calculates maximum likelihood estimates (MLEs) of haplotype frequencies from general nuclear families with an arbitrary number of children via the EM-algorithm for up to 20 SNPs. For more loci, we have implemented a locus-iterative mode of the EM-algorithm, which gives reliable approximations of the MLEs for up to 63 SNP loci, or less when multi-allelic markers are incorporated into the analysis. Missing genotypes can be handled as well. The program is able to distinguish cases (haplotypes transmitted to the first affected child of a family) from pseudo-controls (non-transmitted haplotypes with respect to the child). We tested the performance of FAMHAP and the accuracy of the obtained haplotype frequencies on a variety of simulated data sets. The implementation proved to work well when many markers were considered and no significant differences between the estimates obtained with the usual EM-algorithm and those obtained in its locus-iterative mode were observed. We conclude from the simulations that the accuracy of haplotype frequency estimation and reconstruction in nuclear families is very reliable in general and robust against missing genotypes.

Algorithms↗
PubMed2026

Genomic insights into Aeromonas infections in diarrheal patients: high diversity, emerging resistance, and potential outbreak in Beijing.

BACKGROUND: Aeromonas species are ubiquitous aquatic bacteria that have emerged as significant foodborne enteric pathogens worldwide, yet their genomic landscape in clinical settings remains poorly delineated, particularly in Beijing. METHODS: To address this gap, we performed active surveillance for Aeromonas among 691 consecutive diarrheal outpatients in a Beijing district from January to December 2024. Isolates were recovered using enrichment culture coupled with PCR screening and identified by MALDI-TOF MS. Antimicrobial susceptibility was tested against 17 agents. Whole-genome sequencing was conducted on all isolates, enabling average nucleotide identity (ANI) analysis, comprehensive annotation of antimicrobial resistance and virulence genes, multilocus sequence typing (MLST), and core-genome SNP (cgSNP)-based phylogenetics. RESULTS: Aeromonas was detected in 3.3% (23/691) of patients, with Aeromonas veronii (56.52%, 13/23) and Aeromonas caviae (26.09%, 6/23) predominating. Co-infections with other enteric pathogens occurred in 65.2% of positive cases. Resistance rates were notably high for ampicillin/ampicillin-sulbactam (78.26%), nalidixic acid (56.52%), and ertapenem (21.73%), and 65.21% of isolates were multidrug-resistant. Genotypic-phenotypic concordance was robust, with &#x3b2;-lactamase genes ampS (60.87%) and blaCEPH-A3 (47.83%) being most prevalent. Strikingly, mcr-3.25 and mcr-3.3, which belong to the mcr family (originally described as mobile colistin resistance genes), were identified in 8.70% of isolates, exhibiting perfect correlation with phenotypic resistance. Plasmer analysis suggested both mcr genes to be chromosomally encoded. Comparative genomic analysis of virulence-associated genes revealed striking species-specific specialization: A. veronii predominantly carried complete T3SS clusters (61.5%), A. caviae and Aeromonas enteropelogenes were enriched in T6SS genes, and a single A. dhakensis isolate possessed an extensive arsenal including T3SS, T6SS, and a full RTX toxin cluster. MLST resolved the 23 isolates into 22 sequence types, 18 of which were novel. Phylogenetic reconstruction identified a tight monophyletic cluster of three A. veronii isolates (9-27 SNP differences) recovered within a 96-h window, suggestive of a potential cluster that warrants further epidemiological investigation. Comparative genomic analysis of the rare species Aeromonas allosaccharophila demonstrated that the Beijing clinical isolate S14 differs from the U.S. clinical strain ATCC 35942 by 42,099 SNPs, confirming its distinct genetic lineage. CONCLUSION: Collectively, this study delineates high genetic diversity, emerging chromosomal colistin resistance, and species-specific virulence specialization among Aeromonas isolates from diarrheal patients in Beijing. The detection of a potential outbreak cluster and a rare clinical isolate underscores the power of genomics-based surveillance for detecting and mitigating foodborne pathogen threats.

Aeromonas↗
PubMed2007

Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes.

Gene-gene interaction analyses have been suggested as a potential strategy to help identify common disease susceptibility genes. Recently, evidence of a statistical interaction between polymorphisms in two negative immunoregulatory genes, CBLB and CTLA4, has been reported in type 1 diabetes (T1D). This study, in 480 Danish families, reported an association between T1D and a synonymous coding SNP in exon 12 of the CBLB gene (rs3772534 G>A; minor allele frequency, MAF=0.24; derived relative risk, RR for G allele=1.78; P=0.046). Furthermore, evidence of a statistical interaction with the known T1D susceptibility-associated CTLA4 polymorphism rs3087243 (laboratory name CT60, G>A) was reported (P<0.0001), such that the CBLB SNP rs3772534 G allele was overtransmitted to offspring with the CTLA4 rs3087243 G/G genotype. We have, therefore, attempted to obtain additional support for this finding in both large family and case-control collections. In a primary analysis, no evidence for an association of the CBLB SNP rs3772534 with disease was found in either sample set (2162 parent-child trios, P=0.33; 3453 cases and 3655 controls, P=0.69). In the case-only statistical interaction analysis between rs3772534 and rs3087243, there was also no support for an effect (1994 T1D affected offspring, and 3215 cases, P=0.92). These data highlight the need for large, well-characterized populations, offering the possibility of obtaining additional support for initial observations owing to the low prior probability of identifying reproducible evidence of gene-gene interactions in the analysis of common disease-associated variants in human populations.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Evidence for a novel rheumatoid arthritis susceptibility locus on chromosome 6p.

OBJECTIVE: To investigate whether the large linkage peak on chromosome 6p harbors rheumatoid arthritis (RA) susceptibility loci in addition to the well-characterized HLA-DRB1 gene. METHODS: DNA samples obtained from 377 UK RA affected sibling pair (ASP) families, comprising test (181 ASPs) and replication (196 ASPs) cohorts, were used for linkage analysis. Three hundred eighty-four patients with RA derived from a subset of 192 ASPs were compared with a panel of 288 unrelated healthy controls for association studies. Samples were genotyped for 35 microsatellites and 25 single-nucleotide polymorphisms (SNPs). RESULTS: In the test cohort, the maximum logarithm of odds (LOD) score was obtained over D6S1260 (LOD 7.1). Evidence for linkage to the telomeric portion of the peak was increased in subsets of ASPs in which both individuals had erosive disease or both carried 2 copies of the shared epitope. HLA-A, HLA-DRB1, and 8 additional markers showed evidence of linkage in the presence of association with RA (using the extended transmission disequilibrium test [ETDT]). The positive ETDT result for 2 adjacent markers (D6S1665 and 210901-4) mapping to the telomeric end of the linked region ( approximately 11 Mb from DRB1) was replicated (for D6S1665) in the second cohort of ASPs. Haplotypic overtransmission of pairwise combinations between D6S1665*7 and 210901-4*4 was identified through the TDTPhase program. Multipoint conditional analysis showed this effect to be independent of HLA-DRB1. SNP-based association studies of the region identified a 4-marker haplotype in the DEK gene that was significantly associated with RA (P = 0.009). CONCLUSION: Evidence has been presented for an RA susceptibility locus mapping under the linkage peak on 6p, 11 Mb telomeric of HLA-DRB1. Preliminary association data implicate the gene DEK.

Arthritis, Rheumatoid↗
PubMed2002

SNP genotyping with fluorescence polarization detection.

When a fluorescent molecule is excited by plane polarized light, the fluorescence emitted is also polarized. The degree of fluorescence polarization (FP) detected, under constant temperature and solvent viscosity, is proportional to the molecular weight of the dye molecule. By monitoring the FP of a fluorescent dye, one can detect significant changes in the molecular weight of the molecule without separation or purification. Because the size of the probe is altered in the course of a number of single nucleotide polymorphism (SNP) genotyping reactions, FP is therefore an excellent detection mechanism for these assays. Indeed, FP detection can be used in SNP genotyping with the primer extension TaqMan((R)) and Invader((R)) assays. Use of FP detection makes it possible to reduce the cost of TaqMan((R)) and Invader((R)) probes by abrogating the need for a fluorescence quencher. Moreover, inexpensive, unpurified, and unlabeled probes are used in the primer extension reaction with FP detection. As an end-point detection mechanism, FP detection is suitable for high-throughput SNP genotyping.

DNA Mutational Analysis↗
PubMed2005

Signature of recent historical events in the European Y-chromosomal STR haplotype distribution.

Previous studies of human Y-chromosomal single-nucleotide polymorphisms (Y-SNPs) established a link between the extant Y-SNP haplogroup distribution and the prehistoric demography of Europe. By contrast, our analysis of seven rapidly evolving Y-chromosomal short tandem repeat loci (Y-STRs) in over 12,700 samples from 91 different locations in Europe reveals a signature of more recent historic events, not previously detected by other genetic markers. Cluster analysis based upon molecular variance yields two clearly identifiable sub-clusters of Western and Eastern European Y-STR haplotypes, and a diverse transition zone in central Europe, where haplotype spectra change more rapidly with longitude than with latitude. This and other observed patterns of Y-STR similarity may plausibly be related to particular historical incidents, including, for example, the expansion of the Franconian and Ottoman Empires. We conclude that Y-STRs may be capable of resolving male genealogies to an unparalleled degree and could therefore provide a useful means to study local population structure and recent demographic history.

Chromosomes, Human, Y↗
PubMed2004

An association study in essential hypertension using functional polymorphisms in lymphotoxin-alpha gene.

BACKGROUND: Lymphotoxin-alpha (LTA), a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The substance LTA mediates a wide variety of inflammatory, immunostimulatory, and antiviral responses. In 2002, LTA was identified as a major risk factor for myocardial infarction (MI) in Japanese individuals, in a large-scale case-control study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers in the whole human genome. Essential hypertension (EH) is thought to be a multifactorial disorder involved in endothelial dysfunction and atherosclerosis. Although hypertension is one of the greatest risk factors for MI, there have been no reports estimating the association between EH and LTA. The aim of the present study was to evaluate the association between EH and the LTA gene. METHODS: In the present study, we assessed the association between EH and SNP and haplotypes of the LTA gene in a case-control study of 202 EH patients and 217 age-matched normotensive control subjects. RESULTS: The overall distribution of genotypes for each SNP did not significantly differ between the two groups. Furthermore, the haplotype analysis revealed no association between the EH and normotensive groups. CONCLUSIONS: Polymorphisms of the LTA gene were not associated with EH. This finding suggests differences in genetic backgrounds between EH and MI.

Case-Control Studies↗
PubMed2005

Case-control association study of the close homologue of L1 (CHL1) gene and schizophrenia in the Chinese population.

The close homolog of L1 (CHL1), located on human chromosome 3p26.1, is a newly identified member of the L1 family of cell adhesion molecules which play important roles in cell migration, axonal growth, and synaptic remodeling. A positive association has been reported between a missense polymorphism in CHL1 gene and schizophrenia in the Japanese population [Sakurai, K., Migita, O., Toru, M., Arinami, T., 2002. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. Mol. Psychiatry 7, 412-415]. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. In order to test this finding, we genotyped four SNPs in the gene in the Han Chinese population using a sample of 560 cases and 576 controls. Analysis of allele frequencies in both samples also showed strong association between SNP rs2272522 (the same marker studied by K. Sakurai) and the disease (X2=31.591, P<0.000001, OR=1.745, 95% CI=1.435-2.121). Our results confirm the positive association between CHL1 gene and schizophrenia and indicate that CHL1 may be involved in the etiology of schizophrenia.

Adult↗
PubMed2005

Analyzing genes using closing and replicating circles.

During the past two years, significant breakthroughs have been achieved in genetic analyses through the application of technologies based on analytical DNA-circularization reactions. Padlock probes and molecular inversion probes have enabled parallel, high-throughput single nucleotide polymorphism (SNP) genotyping at increased scales, whereas, at the other end of the analysis spectrum, DNA molecules in individual cells have been genotyped, in situ, using padlock probes and rolling-circle amplification (RCA). This review describes the recent developments in the technologies that use specific DNA circularization, coupled to DNA amplification through PCR or rolling-circle amplification, and addresses the great potential of these tools.

Animals↗
PubMed2006

Identification of base pairs in single-nucleotide polymorphisms by MutS protein-mediated capillary electrophoresis.

Single-nucleotide polymorphisms (SNPs) are widespread genomic variations, which are associated with serious health disorders and drug resistance. Multiple clinical applications and studies of global population genetics require fast and informative analysis of SNPs. Most of conventional methods sense the presence of the SNP but cannot identify the base pair in it. Here we report simple identification of base pairs in SNPs without DNA sequencing. Our approach is based on the unique ability of MutS protein to bind different single-nucleotide mismatches in DNA with different affinities. Conceptually, the DNA in question is mixed with reference DNA, melted, and reannealed. If the DNA in question has an SNP, the products of reannealing will have two different single-nucleotide mismatches, which provide a base-pair-specific signature of the SNP. The products of reannealing are mixed with MutS, equilibrated, and separated by equilibrium capillary electrophoresis of equilibrium mixtures with MutS in the run buffer. The pattern of migration times of DNAs with mismatches is used for unequivocal identification of the base pair in the SNP. In addition to its ability to identify base pairs in SNPs, the new analytical approach is fast, simple, highly sensitive, and requires no quantitation. It will find applications in studies of heterogeneity of base pairs in known SNPs in large human populations.

Base Pairing↗
PubMed2005

Genetic stratification of pathogen-response-related and other variants within a homogeneous Caucasian Irish population.

Selection pressures from pathogens impact on the worldwide geographic distribution of polymorphisms in certain pathogen-response-associated genes. Such gene-specific effects could lead to confounding by geographic disease associations. We wished to determine if such constraints impinge on the genetic structure of a population of Irish patients and whether variants associated with responses to pathogens showed greater stratification. The counties of origin of each subject's grandparents were used as the geographic variable. F(st), proportional to the extent of population structure, was low (mean F(st)=0.004 across 25 SNPs, range 0.001-0.008) and it was not significantly higher for pathogen response SNPs (F(st)=0.004) than for other SNPs (F(st)=0.003, P=0.21). Correspondence analysis revealed weak trends primarily in approximately northeast to southwest and secondarily in northwest to southeast directions. One-dimensional spatial autocorrelation analysis revealed a weak (Moran's I autocorrelation of -0.10) tendency for SNP frequencies to diverge with greater distance. Two-dimensional autocorrelation indicated a northeast to southwest gradient that was similar for both the pathogen response and other SNPs. The southeastern county, Wexford, showed a distinctive pattern, perhaps consistent with Anglo-Norman settlements. In conclusion, these results indicate that pathogen response SNPs do not exhibit significantly more population structure than other SNPs within this Caucasian population. This suggests that the specific population structure of particular genes may not typically be a cause of strong confounding in genetic studies where population structure is controlled.

Arylsulfotransferase↗
PubMed2002

Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia.

Prior evidence has supported the existence of multiple susceptibility genes for schizophrenia. Multipoint linkage analysis of the 270 Irish high-density pedigrees that we have studied, as well as results from several other samples, suggest that at least one such gene is located in region 6p24-21. In the present study, family-based association analysis of 36 simple sequence-length-polymorphism markers and of 17 SNP markers implicated two regions, separated by approximately 7 Mb. The first region, and the focus of this report, is 6p22.3. In this region, single-nucleotide polymorphisms within the 140-kb gene DTNBP1 (dystrobrevin-binding protein 1, or dysbindin) are strongly associated with schizophrenia. Uncorrected, empirical P values produced by the program TRANSMIT were significant (P<.01) for a number of individual SNP markers, and most remained significant when the data were restricted to include only one affected offspring per nuclear family per extended pedigree; multiple three-marker haplotypes were highly significant (P=.008-.0001) under the restricted conditions. The pattern of linkage disequilibrium is consistent with the presence of more than one susceptibility allele, but this important issue is unresolved. The number of markers tested in the adjacent genes, all of which are negative, is not sufficient to rule out the possibility that the dysbindin gene is not the actual susceptibility gene, but this possibility appears to be very unlikely. We conclude that further investigation of dysbindin is warranted.

Animals↗