Suchergebnisse

Background: The strong association between HLA-B27 and spondyloarthritis (SpA) has demonstrated that typing the HLA-B27 antigen is a crucial step in diagnosis and aids in defining the progression and severity of disease. Objective: To describe the frequency of HLA-B27 in Colombian individuals with clinical manifestations associated with SpA. Materials and Methodology: We retrospectively analyzed 4109 HLA-B27 typing requests to the Hospital Militar Central and the Instituto de Referencia Andino from Colombian individuals with clinical signs suggestive of SpA between 2009 and 2012. We used basic digital cytometry followed by Polymerase Chain Reaction with sequence specific primers when confirmation was needed. We determined the frequency of HLA-B27 in the population and levels of association of HLA-B27 with SpA. Results: Our population included 1585 men (36.8%) and 2524 women (61.4%). The predominant age range was between 19 and 45 years (49.9%). The majority (95.4%) of the study population came from the Andean region and eastern plains. The most frequent clinical manifestations were peripheral. Only a small fraction (12.1%) of the 4109 subjects was HLA-B27 positive. Of those, 56.9% were male, and 54.7% were between 19 and 45 years old. In contrast, when rheumatologists referred the HLA B27, 64% were found to be positive. Conclusion: The frequency of the HLA-B27 allele in individuals with clinical signs suggestive of SpA was low, in accordance with the lower prevalence found in Colombian patients diagnosed with SpA compared to American and European population.

ABSTRACT Background: The landscape of coronavirus disease in Nigeria is very undulating with established uncertainty due to blatant disregard to genomics research by government health care institutions. As other countries in the west are documenting Covid-19 disease genomics variations among her populace, few research efforts are made by a private university to replicate such data in Nigeria. The objective of this case study was to identify genetic variations associated with severe Covid-19 disease, by whole genome sequencing on a heathy adult Nigerian. Methods: Buccal swabs were self-collected and DNA extracted, quantified, normalised before sequencing on the high-throughput MGI DNBSEQ-T7 DNA sequencer using Nebula genomics platform. Raw sequences in FASTQ files were assembled in contigs or chromosomes using the Gene iobio pipeline. DNA sequences were aligned with integrated genome viewer (IGV) to the human reference genome GRCh38 (hg38) for single nucleotide polymorphism (SNP) variant calls, deletions and insertions. The genetic variations were compared with the recent genome wide association study (GWAS) implicating 8 genetic loci associated with critical covid-19 disease. Results: Five (5) out of the eight (8) genetic variants associated with severe covid-19 were identified in the healthy subject. The highest number of SNPs occurred in Leucine Zipper Transcription Factor Like 1 (LZTFL1) with 147 SNPs, followed by 100 SNPs observed in Oligoadenylate synthetase 1 (OAS1). Six (6) missense variants were observed in Coiled-Coil Alpha-Helical Rod Protein 1 (CCHCR1), all occurring in heterozygous pattern. The SNP in rs3131294 for variant Notch receptor 4 (NOTCH4) located at chr6:32220606 was present in 90% of the allele frequency, while the variant found in Dipeptidyl peptidase (DPP9) on rs2109069 located in chr19:4719431 implicated in GWAS and in this case study had 38% allele frequency. Conclusion: This case study has demonstrated the importance of genomics study that has the potential to play significant roles ...

Abstract Background Animal identification is pivotal in governmental agricultural policy, enabling the management of subsidy payments, movement of livestock, test scheduling and control of disease. Advances in bovine genomics have made it possible to utilise inherent genetic variability to uniquely identify individual animals by DNA profiling, much as has been achieved with humans over the past 20 years. A DNA profiling test based on bi-allelic single nucleotide polymorphism (SNP) markers would offer considerable advantages over current short tandem repeat (STR) based industry standard tests, in that it would be easier to analyse and interpret. In this study, a panel of 51 genome-wide SNPs were genotyped across panels of semen DNA from 6 common breeds for the purposes of ascertaining allelic frequency. For SNPs on the same chromosome, the extent of linkage disequilbrium was determined from genotype data by Expectation Maximization (EM) algorithm. Minimum probabilities of unique identification were determined for each breed panel. The usefulness of this SNP panel was ascertained by comparison to the current bovine STR Stockmarks II assay. A statistically representative random sampling of bovine animals from across Northern Ireland was assembled for the purposes of determining the population allele frequency for these STR loci and subsequently, the minimal probability of unique identification they conferred in sampled bovine animals from Northern Ireland. Results 6 SNPs exhibiting a minor allele frequency of less than 0.2 in more than 3 of the breed panels were excluded. 2 Further SNPs were found to reside in coding areas of the cattle genome and were excluded from the final panel. The remaining 43 SNPs exhibited genotype frequencies which were in Hardy Weinberg Equilibrium. SNPs on the same chromosome were observed to have no significant linkage disequilibrium/allelic association. Minimal probabilities of uniquely identifying individual animals from each of the breeds were obtained and were observed to be superior to those conferred by the industry standard STR assay. Conclusions The 43 SNPs characterised herein may constitute a starting point for the development of a SNP based DNA identification test for European cattle.

Background:Myeloproliferative leukemia virus (MPL) plays an important role in the development of megakaryocytes and platelets as well as the self-renewal of haematopoietic stem cells. Recently, numerous MPL mutations have been identified in MPN and reported by researchers. These mutations alter the normal regulatory mechanisms and lead to autonomous activation or signaling deficiencies. The present study aimed to detect the frequency of MPL (W515L)mutation gene among Sudanese patients with polycythemia vera (PV).It may lead to new diagnostic criteria or therapy design. Materials and methods: This was a descriptive cross sectional study in which a total of 37 patients with polycythemia vera were enrolled in this study, DNA was extracted from patients' blood samples by using salting out method, and analyzed for the detection of MPL(W515L) mutation by using allele specific polymerase chain reaction (ASPCR).Laboratory results and patient's data were analyzed using statistical packing for social sciences program(SPSS). Results:A total of 37 Sudanese patients attended military hospitals that have been diagnosed with polycythemia vera were enrolled in this study. 36(97.3%) of them were males, one (2.7%) females; age ranged between 23-74 years The present study showed that 10(27.0%) patients out of 37 were positive for MPL (W515L) mutation, and all of them were males. Conclusion:This study concluded that the frequency of MPL W515L mutation in Sudanese patients with polycythemia vera is 27%.

Bioinformatic Analysis of Evolutional Conservatism and Functional Significance of Microsatellite Alleles of Human 14Q13.2 Region Associated with Type 2 Diabetes Mellitus
The paper deals with bioinformatic and statistical analysis of the possible functional significance of the previously shown association of several microsatellite alleles in intron 6 of the human proteasome core particle PSMA6 gene (HSMS006) and four other microsatellites localised upstream in human chromosome 14q13.2 (HSMS801, HSMS702, HSMS701, HSMS602) with type 2 diabetes mellitus in Latvia and Botnia, Finland. Genotype analysis revealed that (CAA)8/(CAA)8 homozygotes of the HSMS602 marker were never found in Type 2 diabetes patients, although 6.56% of the individuals from the control groups were the (CAA)8/(CAA)8 homozygotes. For the HSMS801 marker the (AC)21/(AC)23 genotype was never found in the case group and in the control group it was detected with a frequency 4.40%; these differences were statistically significant (P < 0.05). In contrast to the Latvian population, the distribution of genotype frequencies in cases and controls taken from the Botnian dataset was almost similar. Haplotype analysis showed that in the Latvian population besides haplotypes including alleles differently represented in case and control groups, a combination of some alleles almost equally represented in both groups formed combinations that were more characteristic of either the case group or the control group. This indicates probable independent functional significance of these haplotypes that warrants further investigation. In the Botnian population, more allele combinations were observed, and the distribution of haplotypes in case and control groups differed from that observed in Latvia. The observed haplotype distributions might reflect differences between the studied populations: a homogenous and isolated Botnian vis-à-vis a mixed Latvian population. Linkage disequilibrium (LD) analysis of data on the Latvian population revealed nine of ten two-allele combinations manifesting a high LD. HSMS006 and HSMS602 combination had a low LD; among the analysed markers these were situated at the largest distance from one another. Data on the Botnian population showed that haplotypes in eight of ten combinations had a high LD, including the HSMS006 and HSMS602 combinations. It appears that the two populations differ also in linkage disequilibrium of two-loci haplotypes. Theoretical analysis of a potential functional role of the polymorphisms indicated the significance of the microsatellite length of HSMS602 and HSMS006 for the formation of DNA hairpins. The whole genomic region appears to be conservative in mammals.

Objective: Until recently, celiac disease was considered to be rare in China. We aimed to estimate its true status. Methods: By searching the MEDLINE database and four Chinese full-text databases (CNKI, CBM, VIP and WANFANG) (up to August 2012), as well as two HLA allele frequency net databases and the Chinese Statistics Yearbook databases, we systematically reviewed the literature on definite and suspected cases of celiac disease, the predisposing HLA allele frequencies, and on gluten exposure in China. Meta-analysis was performed by analyzing DQ2, DQ8 and DQB1*0201 gene frequencies and heterogeneity in populations from different geographic regions and ethnicities in China. Results: At present, the number of reported celiac disease cases is extremely low in China. The frequencies of the HLA-DQ2.5 and HLA-DQ8 haplotypes were 3.4% (95% confidence interval 1.3-5.5%) and 2.1% (0.1-4.1%), respectively. HLA-DQ2 and HLA-DQ8 antigen frequencies were 18.4% (15.0-21.7%) and 8.0% (4.5-11.4%), respectively. The frequency of the DQB1*0201 allele was 10.5% (9.3-11.6%) and it was more common in the northern Chinese than in the southern Chinese populations. The chance of being exposed to gluten is rapidly increasing all over China nowadays. Conclusion: The data on HLA haplotyping, in conjunction with increasing wheat consumption, strongly suggests that the occurrence of celiac disease is more common in China than currently reported. Coordinated measures by the Chinese government, medical and agricultural research institutions, and food industries, would be justified to create more awareness about celiac disease and to prevent it becoming a medical and societal burden.

The use of genetic methods and data has a long history in anthropology. Following dramatic growth in anthropological genetic field studies in the 1960s and 1970s, the revolution in molecular genetic methods during the 1980s spurred another period of growth and expansion. The earlier emphasis on examination of the role of alternative evolutionary mechanisms in structuring allele frequency variation within and between populations is reflected today in a renewed focus on unraveling demographic history using highly informative molecular markers. The existence of large, publicly available molecular genetic databases, coupled with advances in analytical methods, makes it possible to tackle a wide variety of problems in human evolution not possible with classical markers and traditional analytical methods, These recent advances will help frame the nature of research in the discipline in the near term. [Keywords; human evolutionary genetics, phylogenetics, molecular markers, genetic variation, population structure]

Buffalo breeding in Ukraine is an ancient traditional branch of animal husbandry of the Crimean Tatars and Rusyns of Transcarpathia. Basically, "Ukrainian" buffaloes belong to the river buffalo (Bubalus bubalis) and are bred for dairy and meat production. Polymorphism of genes associated with dairy productivity will allow breeding buffaloes taking into account the "desired" genotypes in relation to economically useful traits. The paper dwells on studying allelic polymorphisms of beta-casein (β-CN), kappa-casein (CSN3) and beta-lactoglobulin (β-LG) genes in population of water buffaloes bred in Ukraine using PCR followed by restriction hydrolysis of the formed fragments (PCR-RFLP). Results of study of the "Ukrainian" population of water buffaloes are discussed, namely: the frequency of genotypes and alleles at the loci of beta-casein, kappa-casein and beta-lactoglobulin genes. Amplified fragment β-CN with the length of 121 bp was digested with DdeI restriction enzyme. A feature of the allelic spectrum of the beta-casein gene (β-CN) in the studied population was absence of A1 allele. All animals carried the β-CNA2A2 genotype of beta-casein gene, respectively, β-CNA2 allele frequency was 1.0. For the CSN3 gene, an amplified fragment in 273 bp was digested with HinfI restriction enzyme. A 100% predominance of animals with the most preferred homozygous CSN3BB genotype was revealed. During the β-LG gene study process, an amplified fragment with a size of 247 bp was digested with HaeIII. It has been determined that the most frequent was allele βLGA and genotype βLGAA of beta-lactoglobulin gene (0.96 and 0.92, respectively). Heterozygous β-LGAB genotype is present in 8 % of buffaloes. The research results are of interest in the field of molecular genetic analysis of the buffalo genome, which are the source of specific properties. The data obtained can be useful for preserving and increasing the genetic diversity of the "Ukrainian" population of water buffaloes, as well as for obtaining valuable products from buffaloes.

<i>Objective:</i> Endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphisms are under extensive study worldwide due to their suggested role in cardiovascular disorders. This polymorphism had gained more attention since several reports suggest its association with hypertension and coronary artery disease (CAD). Asian Indians are highly susceptible to ischemic heart dis eases. We determined the prevalence of eNOS Glu298 Asp polymorphism in 139 healthy volunteers from Delhi and the surrounding areas. The subjects were recruited from those who willingly participated in this study in response to a publicized call and a standard questionnaire. Male to female ratio was 2.7:1 due to the larger number of male participants in this investigation. This, however, does not represent normal male to female distribution in the area. Despite the male bias, this investigation was justified. The prevalence of CAD in males is about 3 times higher in this region and no data had so far been available on the distribution of this polymorphism from India. <i>Method:</i> The eNOS Glu298Asp polymorphism was studied by PCR-RFLP. <i>Results:</i> Distribution of genotype GG, GT and TT in the study subjects was found to be 71.22, 28.06 and 0.72%, respectively, and allele frequency was G,0.853;T,0.147. <i>Conclusion:</i> T allele had been described as susceptibility allele for CAD in several population studies. The frequency of the T allele was found to be two times higher in our subjects than that reported for Japanese and Korean populations. This study does not provide any direct evidence for eNOS gene disease associations but is the first report on the prevalence of eNOS Glu298Asp gene polymorphism in Indian subjects. Whether the observed pattern of eNOS Glu298Asp polymorphism contributes to the greater susceptibility of Asian Indians to CAD as compared to the other population groups, needs to be investigated.

AbstractA requirement for performing robust genetic and statistical analyses on twins is correctly assigned zygosities. In order to increase the power to detect small risk factors of disease, zygosity testing should also be amenable for high throughput screening. In this study we validate and implement the use of a panel of 50 single nucleotide polymorphisms (SNPs) for reliable high throughput zygosity testing and compare it to a panel of 16 short tandem repeats (STRs). We genotyped both genomic (gDNA) and whole genome amplified DNA (WGA DNA), ending up with 47 SNP and 11 STR markers fulfilling our quality criteria. Out of 99 studied twin pairs, 2 were assigned a different zygosity using SNP and STR data as compared to self reported zygosity in a questionnaire. We also performed a sensitivity analysis based on simulated data where we evaluated the effects of genotyping error, shifts in allele frequencies and missing data on the qualitative zygosity assignments. The frequency of false positives was less than 0.01 when assuming a 1% genotyping error, a decrease of 10% of the observed minor allele frequency compared to the actual values and up to 10 missing markers. The SNP markers were also successfully genotyped on both gDNA and WGA DNA from whole blood, saliva and filter paper. In conclusion, we validate a robust panel of 47 highly multiplexed SNPs that provide reliable and high quality data on a range of different DNA templates.

Hepatitis C virus (HCV) is a liver disease that affects14 million people. Feasible research was conducted for identifying the genotypes and allele frequency of some single nucleotide polymorphisms (SNPs) of the IL-28β genes and their predictive role in disease incidence in Iraqi patients. The SNPs (rs28416813, rs4803219, rs11881222, and rs8103142) of IL-28β have been associated with susceptibility to several diseases. Ninety eight (98) HCV patients were included in this research; with average age ± SE (42.28 ± 3.44) years. Also, 80 healthy people (with average age ± SE (29.40 ± 2.84) years) were included as a control group. The SNPs were detected by allele-specific PCR (polymerase chain reaction) using specific primers. The results showed that IL-28β rs28416813 CC genotype was increased in HCV patients significantly while rs4803219 CC and CT genotypes were increased in the HCV patients significantly and insignificantly, respectively. Moreover, rs4803222 GA and AA genotypes frequencies were elevated in HCV patients insignificantly and significantly, respectively. Finally, IL28β rs8103142 gene polymorphism displayed overrepresentation of CT and TT genotypes incidence in hepatitis C patients highly significantly and non-significantly, respectively, as compared to control. The current data suggested that IL28β genetics may have an effect on susceptibility with HCV infection in Iraqis.

The 1691G>AFVvariant has been described as a common genetic risk factor in venous thromboembolism. The purpose of this study was to provide a further frequency value for 1691G>AFVin Poland and to collate summary data from Central (Poland, Czech, Slovakia), Eastern (Russia, Belarus, Ukraine) and South-Eastern (Slovenia, Croatia, Bosnia and Herzegovina, Serbia, Montenegro, Macedonia, Bulgaria) European countries. For this purpose in 2007 the 1691G>AFVvariant was analyzed by polymerase chain reaction-restriction fragment length polymorphism from DNA collected in 2005-2006. We studied 650 subjects: 400 newborns and 250 older individuals (mean age 46.1 y) from Poland and compared results with reports from other countries, as well as with the frequency trend of 845G>AHFEacross South-Eastern European countries using centroid cities. From our 1691G>AFVstudy we identified 626 GG homozygotes, 23 GA heterozygotes, and i AA homozygote (n = 650), giving an A allele frequency of 1.9%, and a summed frequency value for Poland of 2.0% (n = 1588); the frequency in Central European countries was 3.9% (n = 4559), mostly due to the high value in the Czech Republic: 5.1% (n = 2819); the South-Eastern European countries had 2.5% (n = 2410). Among the Eastern European countries the 1691G>AFVallele frequency was 1.9% (n=791), between the South-Eastern and Eastern European countries there was no significant difference (p=0.17). We confirm that the 1691G>AFVallele frequency in Poland, as well as other countries compared, is significantly lower than that in Czech.

18 páginas, 7 tablas. ; Selection and random genetic drift are the two main forces affecting allele frequencies in common bean breeding programs. Therefore, knowledge on allele frequency changes attributable to these forces is of fundamental importance for breeders. The changes in frequencies of alleles of biochemical markers were examined in F2 to F7 populations derived from crosses between cultivated Mesoamerican and Andean common bean accessions (Phaseolus vulgaris L.). Biochemical markers included the seed proteins phaseolin, lectin and other seed polypeptides, and six isozymes. The Schaffer's test detected a high significant linear trend of the 63% of the polymorphic loci studied, meaning that directional selection was acting on those loci. Associations between seed size traits, phaseolin seed-storage protein and isozyme markers were detected based on the comparisons of the progeny genotypic means. In the interracial populations the intermediate form PhaH/T, b6, and Rbcs 98 alleles had a positive effect on seed size. In the inter-gene pool populations, a higher transmission of Mesoamerican alleles in all loci was showed, although the Andean alleles PhaT, Skdh 100 , Rbcs 98 , and Diap 100 showed positive effects on seed weight. Our results suggest that phaseolin and other seed proteins markers are linked to loci affecting seed size. These markers have good potential for improving the results of the selection and should be considered as a strategy for germplasm enhancement and to avoid the reduced performance of the inter-gene pool populations. ; Research was supported by the projects AGF97-0324 and AGL2005-01268/AGR from the Spanish Government, PGIDIT02RAG40301PR from the Galician Government (Spain), and EU-FEDER Funds. A. M. González thanks her fellowship to Ministry of Education, Culture and Sports of Spain. M. De la Fuente is grateful to the Xunta de Galicia for awarding her a fellowship grant. ; Peer reviewed

<i>Background:</i> The wide use of genome wide association studies (GWAS) has led to the successful identification of multiple genetic susceptibility variants to several complex human diseases. Given the limited amount of data on genetic variation at these loci in populations of non-European origin, we investigated population variation among 11 population groups for loci showing strong and consistent association from GWAS with several complex human diseases. <i>Methods:</i> Data from the International HapMap Project Phase 3, comprising 11 population groups, were used to estimate allele frequencies at loci showing strong and consistent association from GWAS with any of 26 complex human diseases and traits. Allele frequency summary statistics and F_ST at each locus were used to estimate population differentiation. <i>Results:</i> There is wide variation in allele frequencies and F_ST across the 11 population groups for susceptibility loci to these complex human diseases and traits. Allele frequencies varied widely across populations, often by as much as 20- to 40-fold. F_ST, as a measure of population differentiation, also varied widely across the loci studied (for example, 0.019 to 0.201 for type 2 diabetes, 0.022 to 0.520 for prostate cancer loci, and 0.006 to 0.520 for serum lipid levels). <i>Conclusions:</i> The public health risk posed by any of these risk alleles is likely to show wide variation across populations simply as a function of its frequency, and this risk difference may be amplified by gene-gene and gene-environment interactions. These analyses offer compelling reasons for including multiple human populations from different parts of the world in the international effort to use genomic tools to understand disease etiology and differential distribution of diseases across ethnic groups.

The history of populations or species is of fundamental importance in a variety of areas. Gaining details about demographic, cultural, climatic or political aspects of the past may provide insights that improve the understanding of how populations have evolved over time and how they may evolve in future. Different types of resources can be informative about different periods of time. One especially important resource is genetic data, either from a single individual or a group of organisms. Environmental conditions and circumstances can directly affect the existence and success of a group of individuals. Since genetic material gets passed on from generation to generation, traces of past events can still be detected in today\''s genetic data. For many decades scientists have tried to understand the principles of how external influences can directly affect the appearance and features of populations, leading to theoretical models that can interpret modern day genetic variation in the light of past events. Among other influencing factors like migration, natural selection etc., population size changes can have a great impact on the genetic diversity of a group of organisms. For example, in the field of conservation biology, gaining insights into how the size of a population evolves may assist in detecting past or ongoing temporal reductions of population size. This seems crucial since the reduction in size also correlates with a reduction in genetic diversity which in turn might negatively affect the evolutionary potential of a population. Using computational and population genetics methods, sequences from whole genomes can be scanned for traces of such events and therefore assist in new interpretations of historical details of populations or groups of interest. This thesis focuses on the detection and interpretation of past population size changes. Two approaches to infer particular parameters from underlying demographic models are described. The first part of this thesis introduces two summary statistics which were designed to detect fluctuations in size from genome-wide Single Nucleotide Polymorphism (SNP) data. Demographic inferences from such data are inherently complicated due to recombination and ascertainment bias. Hence, two new statistics are introduced: allele frequency-identity by descent (AF-IBD) and allele frequency-identity by state (AF-IBS). Both make use of linkage disequilibrium information and exhibit defined relationships to the time of the underlying mathematical process. A fast and efficient Approximate Bayesian Computation framework based on AF-IBD and AF-IBS is constructed that can accurately estimate demographic parameters. These two statistics were tested for the biasing effects of hidden recombination events, ascertainment bias and phasing errors. The statistics were found to be robust to a variety of these tested biases. The inference approach was then applied to genome-wide SNP data to infer the demographic histories of two human populations: (i) Yoruba from Africa and (ii) French from Europe. Results suggest, that AF-IBD and AF-IBS are able to capture sufficient amounts of information from underlying data sets in order to accurately infer parameters of interest, such as the beginning, end and strength of periods of varying size. Additionally the results from empirical data suggest a rather stable ancestral population size with a mild recent expansion for Yoruba, whereas the French apparently experienced a rather long-lasting strong bottleneck followed by a drastic population growth. The second part of this thesis introduces a new way of summarizing information from the site frequency spectrum. Commonly applied site frequency spectrum based inference methods make use of allele frequency information from individual segregating sites. Our newly developed method, the 2 point spectrum, summarizes allele frequency information from all possible pairs of segregating sites, thereby increasing the number of potentially informative values from the same underlying data set. These additional information are then incorporated into a Markov Chain Monte Carlo framework. This allows for a high degree of flexibility and implements an efficient method to infer population size trajectories over time. We tested the method on a variety of different simulated data sets from underlying demographic models. Furthermore, we compared the performance and accuracy of our method to already established methods like PSMC and diCal. Results indicate that this non-parametric 2 point spectrum method can accurately infer the extent and times of past population size changes and therefore correctly estimates the history of temporal size fluctuations. Furthermore, the initial results suggest that the amount of required data and the accuracy of the final results are comparable with other publicly available non-parametric methods. An easy to use command line program was implemented and will be made publicly available. In summary, we introduced three highly sensitive summary statistics and proposed different approaches to infer parameters from demographic models of interest. Both methods provide powerful frameworks for accurate parameter inference from genome-wide genetic data. They were tested for a variety of demographic models and provide highly accurate results. They may be used in the settings as described above or incorporated into already existing inference frameworks. Nevertheless, the statistics should prove useful for new insights into populations, especially those with complex demographic histories.