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Search Results: 1 - 10 of 17823 matches for " Mark Seielstad "
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HIV, Stigma, and Rates of Infection: Absence of Evidence
Mark Seielstad
PLOS Medicine , 2007, DOI: 10.1371/journal.pmed.0040054
Pathway-based analysis using reduced gene subsets in genome-wide association studies
Jingyuan Zhao, Simone Gupta, Mark Seielstad, Jianjun Liu, Anbupalam Thalamuthu
BMC Bioinformatics , 2011, DOI: 10.1186/1471-2105-12-17
Abstract: We applied this new method to a published GWAS of psoriasis and identified 6 biologically plausible pathways, after adjustment for multiple testing. The pathways identified in our analysis overlap with those reported in previous studies. Further, using simulations across a range of gene numbers and effect sizes, we demonstrate that the proposed approach enjoys higher power than several other approaches to detect associated pathways.The proposed method could increase the power to discover susceptibility pathways and to identify associated genes using GWAS. In our analysis of genome-wide psoriasis data, we have identified a number of relevant pathways for psoriasis.Genetic association studies aim to detect associations between disease phenotypes and genetic variants. A commonly used tool to establish association between a SNP and a disease is to perform statistical tests of association for each individual SNP marker. A multiple testing correction can then be applied to control the overall type I error. However, such an approach typically captures only a small proportion of the contributing genetic variants. One likely reason is that common and complex diseases result from the joint effects of multiple loci and environmental factors, each of which has a small individual contribution [1,2]. A variety of tests have been proposed to establish the joint association of multiple SNPs with the phenotype.For such joint association analyses, the first category of statistical methods are those that use single SNP p-values or test statistics to construct a new joint test statistic. The Most Significant SNP method (MSS) uses the smallest p-value to declare significance. Fisher's method combines p-values by using negative of the twice of logarithm of product of p-values. Another group of test statistics pools SNPs with relatively strong signals from univariate tests, which include the sum of the K largest test statistics [3], the product of all the tests declared to be significant
Genetic structure of the Mon-Khmer speaking groups and their affinity to the neighbouring Tai populations in Northern Thailand
Wibhu Kutanan, Jatupol Kampuansai, Silvia Fuselli, Supaporn Nakbunlung, Mark Seielstad, Giorgio Bertorelle, Daoroong Kangwanpong
BMC Genetics , 2011, DOI: 10.1186/1471-2156-12-56
Abstract: A large fraction of genetic variation is observed within populations (about 80% and 90% for mtDNA and the Y-chromosome, respectively). The genetic divergence between populations is much higher in Mon-Khmer than in Tai speaking groups, especially at the paternally inherited markers. The two major linguistic groups are genetically distinct, but only for a marginal fraction (1 to 2%) of the total genetic variation. Genetic distances between populations correlate with their linguistic differences, whereas the geographic distance does not explain the genetic divergence pattern.The Mon-Khmer speaking populations in northern Thailand exhibited the genetic divergence among each other and also when compared to Tai speaking peoples. The different drift effects and the post-marital residence patterns between the two linguistic groups are the explanation for a small but significant fraction of the genetic variation pattern within and between them.Northern Thailand consists of many plains and mountains, usually stretching in a north-south direction. Most of this wide area is covered by forests and fertile land that was occupied by large numbers of people since prehistoric times [1].Today, the Tai speaking peoples represent the major linguistic group in Northern Thailand, but archaeological evidence reveals that this area was occupied by Mon-Khmer speaking groups such as Mlabri, H'tin, Lawa, and Mon since the prehistoric period [1]. The first kingdom-level development was the Mon of Haripunchai (750 A.D.-1300 A.D.), and the earliest datable stone inscriptions (from 1218 to 1219 A.D.) mentioned Lawa as another local population [2]. The decline of the Mon kingdom occurred in the thirteenth century when a Tai group migrated from south and south-east China. They conquered the native populations on their southern route until they reached the northern part of what is now Thailand. Some Mon groups fled south to central Thailand, but many remained in this area under the Tai rulers [1]. T
Genetic evidence supports linguistic affinity of Mlabri - a hunter-gatherer group in Thailand
Shuhua Xu, Daoroong Kangwanpong, Mark Seielstad, Metawee Srikummool, Jatupol Kampuansai, Li Jin, The HUGO Pan-Asian SNP Consortium*
BMC Genetics , 2010, DOI: 10.1186/1471-2156-11-18
Abstract: We conducted a genome-wide analysis of genetic variation using more than fifty thousand single nucleotide polymorphisms (SNPs) typed in thirteen population samples from Thailand, including the Mlabri, Htin and neighboring populations of the Northern Highlands, speaking Austro-Asiatic, Tai-Kadai and Hmong-Mien languages. The Mlabri population showed higher LD and lower haplotype diversity when compared with its neighboring populations. Both model-free and Bayesian model-based clustering analyses indicated a close genetic relationship between the Mlabri and the Htin, a group speaking a Tin language.Our results strongly suggested that the Mlabri share more recent common ancestry with the Htin. We thus provided, to our knowledge, the first genetic evidence that supports the linguistic affinity of Mlabri, and this association between linguistic and genetic classifications could reflect the same past population processes.The Mlabri are a hill tribe in northern Thailand, inhabiting a dispersed area along the border with Laos [1,2]. Today, they are a small population of nomadic hunter-gatherers, unusual in a region of almost entirely agricultural economies [3]. The modern population size is estimated at around 300 individuals, with some estimates being as low as 100 [4]. The name Mlabri is a Thai/Lao alteration of the word Mrabri, which appears to derive from a Khmuic term for "people of the forest" - in Khmu, mra means "person" and bri "forest". They are also known locally as Phi Tong Luang or "spirits of the yellow leaves", apparently because they abandon their shelters when the leaves begin to turn yellow with the onset of the dry season.Little is known about the origins of the Mlabri and most evidence comes from linguistic studies. The Mlabri language is classified as a Khmuic language, a subgroup of the Mon-Khmer language in the Austro-Asiatic language family [5]. The available linguistic evidence suggests that the present-day Mlabri language most likely arose from Tin
Transferability of Type 2 Diabetes Implicated Loci in Multi-Ethnic Cohorts from Southeast Asia
Xueling Sim,Rick Twee-Hee Ong,Chen Suo,Wan-Ting Tay,Jianjun Liu,Daniel Peng-Keat Ng,Michael Boehnke,Kee-Seng Chia,Tien-Yin Wong,Mark Seielstad,Yik-Ying Teo ,E-Shyong Tai
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1001363
Abstract: Recent large genome-wide association studies (GWAS) have identified multiple loci which harbor genetic variants associated with type 2 diabetes mellitus (T2D), many of which encode proteins not previously suspected to be involved in the pathogenesis of T2D. Most GWAS for T2D have focused on populations of European descent, and GWAS conducted in other populations with different ancestry offer a unique opportunity to study the genetic architecture of T2D. We performed genome-wide association scans for T2D in 3,955 Chinese (2,010 cases, 1,945 controls), 2,034 Malays (794 cases, 1,240 controls), and 2,146 Asian Indians (977 cases, 1,169 controls). In addition to the search for novel variants implicated in T2D, these multi-ethnic cohorts serve to assess the transferability and relevance of the previous findings from European descent populations in the three major ethnic populations of Asia, comprising half of the world's population. Of the SNPs associated with T2D in previous GWAS, only variants at CDKAL1 and HHEX/IDE/KIF11 showed the strongest association with T2D in the meta-analysis including all three ethnic groups. However, consistent direction of effect was observed for many of the other SNPs in our study and in those carried out in European populations. Close examination of the associations at both the CDKAL1 and HHEX/IDE/KIF11 loci provided some evidence of locus and allelic heterogeneity in relation to the associations with T2D. We also detected variation in linkage disequilibrium between populations for most of these loci that have been previously identified. These factors, combined with limited statistical power, may contribute to the failure to detect associations across populations of diverse ethnicity. These findings highlight the value of surveying across diverse racial/ethnic groups towards the fine-mapping efforts for the casual variants and also of the search for variants, which may be population-specific.
Genetic Association and Expression Studies Indicate a Role of Toll-Like Receptor 8 in Pulmonary Tuberculosis
Sonia Davila ,Martin L. Hibberd,Ranjeeta Hari Dass,Hazel E. E. Wong,Edhyana Sahiratmadja,Carine Bonnard,Bachti Alisjahbana,Jeffrey S. Szeszko,Yanina Balabanova,Francis Drobniewski,Reinout van Crevel,Esther van de Vosse,Sergey Nejentsev,Tom H. M. Ottenhoff,Mark Seielstad
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000218
Abstract: Despite high rates of exposure, only 5–10% of people infected with Mycobacterium tuberculosis will develop active tuberculosis (TB) disease, suggesting a significant role for genetic variation in the human immune response to this infection. Here, we studied TB association and expression of 18 genes involved in the Toll-like receptor (TLR) pathways. Initially, we genotyped 149 sequence polymorphisms in 375 pulmonary TB patients and 387 controls from Indonesia. We found that four polymorphisms in the TLR8 gene on chromosome X showed evidence of association with TB susceptibility in males, including a non-synonymous polymorphism rs3764880 (Met1Val; P = 0.007, odds ratio (OR) = 1.8, 95% c.i. = 1.2–2.7). We genotyped these four TLR8 polymorphisms in an independent collection of 1,837 pulmonary TB patients and 1,779 controls from Russia and again found evidence of association in males (for rs3764880 P = 0.03, OR = 1.2, 95% c.i. = 1.02–1.48). Combined evidence for association is P = 1.2×10?3–6×10?4. In addition, a quantitative PCR analysis indicated that TLR8 transcript levels are significantly up-regulated in patients during the acute phase of disease (P = 9.36×10?5), relative to baseline levels following successful chemotherapy. A marked increase in TLR8 protein expression was also observed directly in differentiated macrophages upon infection with M. bovis bacille Calmette-Guérin (BCG). Taken together, our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB across different populations.
Genome-Wide Expression Profiling Identifies Type 1 Interferon Response Pathways in Active Tuberculosis
Tom H. M. Ottenhoff, Ranjeeta Hari Dass, Ninghan Yang, Mingzi M. Zhang, Hazel E. E. Wong, Edhyana Sahiratmadja, Chiea Chuen Khor, Bachti Alisjahbana, Reinout van Crevel, Sangkot Marzuki, Mark Seielstad, Esther van de Vosse, Martin L. Hibberd
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045839
Abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains the leading cause of mortality from a single infectious agent. Each year around 9 million individuals newly develop active TB disease, and over 2 billion individuals are latently infected with M.tb worldwide, thus being at risk of developing TB reactivation disease later in life. The underlying mechanisms and pathways of protection against TB in humans, as well as the dynamics of the host response to M.tb infection, are incompletely understood. We carried out whole-genome expression profiling on a cohort of TB patients longitudinally sampled along 3 time-points: during active infection, during treatment, and after completion of curative treatment. We identified molecular signatures involving the upregulation of type-1 interferon (α/β) mediated signaling and chronic inflammation during active TB disease in an Indonesian population, in line with results from two recent studies in ethnically and epidemiologically different populations in Europe and South Africa. Expression profiles were captured in neutrophil-depleted blood samples, indicating a major contribution of lymphocytes and myeloid cells. Expression of type-1 interferon (α/β) genes mediated was also upregulated in the lungs of M.tb infected mice and in infected human macrophages. In patients, the regulated gene expression-signature normalized during treatment, including the type-1 interferon mediated signaling and a concurrent opposite regulation of interferon-gamma. Further analysis revealed IL15RA, UBE2L6 and GBP4 as molecules involved in the type-I interferon response in all three experimental models. Our data is highly suggestive that the innate immune type-I interferon signaling cascade could be used as a quantitative tool for monitoring active TB disease, and provide evidence that components of the patient’s blood gene expression signature bear similarities to the pulmonary and macrophage response to mycobacterial infection.
A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians
Eileen Png, Bachti Alisjahbana, Edhyana Sahiratmadja, Sangkot Marzuki, Ron Nelwan, Yanina Balabanova, Vladyslav Nikolayevskyy, Francis Drobniewski, Sergey Nejentsev, Iskandar Adnan, Esther van de Vosse, Martin L Hibberd, Reinout van Crevel, Tom HM Ottenhoff, Mark Seielstad
BMC Medical Genetics , 2012, DOI: 10.1186/1471-2350-13-5
Abstract: In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia.Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4.Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB.Tuberculosis (TB) remains one of the leading causes of infection-associated mortality, with close to 10 million new cases and 2 million deaths annually [1,2]. Although Mycobacterium tuberculosis has infected around a third of the world's population, only 3-10% of those infected develop active disease during their lifetime [3]. More than 90% of infected individuals remain asymptomatic with a latent infection. This indicates that host immune/defense pathways are often highly effective in controlling this disease. Because the infection causes such a burden of disease in those unable to contain the infection, it is important to discover underlying mechanisms to aid the development of more effective interventions such as better vaccines and novel treatments for latent and active infection. Similarly, it is important to identify predictive biomarkers that might identify individuals who are most susceptible to developing active TB disease.Studies of heritability using twins and other familial designs have convincingly implicated a genetic
Genome Wide Association Study (GWAS) of Chagas Cardiomyopathy in Trypanosoma cruzi Seropositive Subjects
Xutao Deng, Ester C. Sabino, Edecio Cunha-Neto, Antonio L. Ribeiro, Barbara Ianni, Charles Mady, Michael P. Busch, Mark Seielstad, the REDSII Chagas study group from the NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II) , International Component
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079629
Abstract: Background Familial aggregation of Chagas cardiac disease in T. cruzi–infected persons suggests that human genetic variation may be an important determinant of disease progression. Objective To perform a GWAS using a well-characterized cohort to detect single nucleotide polymorphisms (SNPs) and genes associated with cardiac outcomes. Methods A retrospective cohort study was developed by the NHLBI REDS-II program in Brazil. Samples were collected from 499 T. cruzi seropositive blood donors who had donated between1996 and 2002, and 101 patients with clinically diagnosed Chagas cardiomyopathy. In 2008–2010, all subjects underwent a complete medical examination. After genotype calling, quality control filtering with exclusion of 20 cases, and imputation of 1,000 genomes variants; association analysis was performed for 7 cardiac and parasite related traits, adjusting for population stratification. Results The cohort showed a wide range of African, European, and modest Native American admixture proportions, consistent with the recent history of Brazil. No SNPs were found to be highly (P<10?8) associated with cardiomyopathy. The two mostly highly associated SNPs for cardiomyopathy (rs4149018 and rs12582717; P-values <10?6) are located on Chromosome 12p12.2 in the SLCO1B1 gene, a solute carrier family member. We identified 44 additional genic SNPs associated with six traits at P-value <10-6: Ejection Fraction, PR, QRS, QT intervals, antibody levels by EIA, and parasitemia by PCR. Conclusion This GWAS identified suggestive SNPs that may impact the risk of progression to cardiomyopathy. Although this Chagas cohort is the largest examined by GWAS to date, (580 subjects), moderate sample size may explain in part the limited number of significant SNP variants. Enlarging the current sample through expanded cohorts and meta-analyses, and targeted studies of candidate genes, will be required to confirm and extend the results reported here. Future studies should also include exposed seronegative controls to investigate genetic associations with susceptibility or resitance to T. cruzi infection and non-Chagas cardiomathy.
Digital Northern Great Plains: A Web-Based System Delivering Near Real Time Remote Sensing Data for Precision Agriculture
Xiaodong Zhang,Santhosh Seelan,George Seielstad
Remote Sensing , 2010, DOI: 10.3390/rs2030861
Abstract: The US Northern Great Plains is one of the world’s most agriculturally productive areas. Growers in the region are eager to adopt modern technology to improve productivity and income. Use of information derived from remote sensing satellites to better manage farms and rangelands while reducing environmental impacts has gained popularity in recent years. However, prohibitive costs and non-availability of near real time remote sensing imagery has slowed the adoption of this technology for in-field decision making. Digital Northern Great Plains (DNGP), a web based remote sensing data dissemination system, was developed to address these drawbacks. It provides end users easy and free access to a variety of imagery and products in near real time. With delivery of archived and current data, DNGP has helped farmers and ranchers reduce operational costs and increase productivity through a variety of innovative applications. Moreover, negative environmental impacts were lessened.
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