313 research outputs found

    Proposed nomenclature for microhaplotypes

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    A Variant in a MicroRNA complementary site in the 3' UTR of the KIT oncogene increases risk of acral melanoma.

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    MicroRNAs (miRNAs) are small ∼22nt single stranded RNAs that negatively regulate protein expression by binding to partially complementary sequences in the 3' untranslated region (3' UTRs) of target gene messenger RNAs (mRNA). Recently, mutations have been identified in both miRNAs and target genes that disrupt regulatory relationships, contribute to oncogenesis and serve as biomarkers for cancer risk. KIT, an established oncogene with a multifaceted role in melanogenesis and melanoma pathogenesis, has recently been shown to be upregulated in some melanomas, and is also a target of the miRNA miR-221. Here, we describe a genetic variant in the 3' UTR of the KIT oncogene that correlates with a greater than fourfold increased risk of acral melanoma. This KIT variant results in a mismatch in the seed region of a miR-221 complementary site and reporter data suggests that this mismatch can result in increased expression of the KIT oncogene. Consistent with the hypothesis that this is a functional variant, KIT mRNA and protein levels are both increased in the majority of samples harboring the KIT variant. This work identifies a novel genetic marker for increased heritable risk of melanoma

    The Microfloral Analysis of Secondary Caries Biofilm around Class I and Class II Composite and Amalgam Fillings

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    <p>Abstract</p> <p>Background</p> <p>Secondary caries is responsible for 60 percent of all replacement restorations in the typical dental practice. The diversity of the bacterial sources and the different types of filling materials could play a role in secondary caries. The aim of this study was to determine and compare the microbial spectrum of secondary caries biofilms around amalgam and composite resin restorations.</p> <p>Methods</p> <p>Clinical samples were collected from freshly extracted teeth diagnosed with clinical secondary caries. Samples were categorized into four groups according to the types of restoration materials and the classification of the cavity. Biofilms were harvested from the tooth-restoration interface using a dental explorer and after dilution were incubated on special agars. The bacteria were identified using the biochemical appraisal system. Statistical calculations were carried out using SPSS11.5 software to analyze the prevalence of the bacteria involved in secondary caries.</p> <p>Results</p> <p>Samples from a total of four groups were collected: two groups were collected from amalgam restorations, each had 21 samples from both Class I and Class II caries; and the other two groups were from composite resin restorations, each had 13 samples from both class I and class II caries. Our results showed: (1) Anaerobic species were dominant in both restoration materials. (2) In terms of the types of individual bacteria, no significant differences were found among the four groups according to the geometric mean of the detected bacteria (P > 0.05). However, there were significant differences among the detected bacteria within each group (P < 0.05). The composition of each bacterium had no statistical difference among the four groups (P > 0.05), but showed significant differences among the detected bacteria in each group (P < 0.05). (3) Among the four groups, there were no significant differences for the detection rate of each bacterium (P > 0.05), however, the detection rate of each bacterium within each group was statistically different among the detected bacteria (P < 0.05).</p> <p>Conclusions</p> <p>The proportion of obligatory anaerobic species was much greater than the facultative anaerobic species in the biofilm of secondary caries. Statistically, the materials of restoration and the location of secondary caries did not show any significant effects on the composition of the microflora.</p

    Increasing the reference populations for the 55 AISNP panel: the need and benefits

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    Ancestry inference for an individual can only be as good as the reference populations with allele frequency data on the SNPs being used. If the most relevant ancestral population(s) does not have data available for the SNPs studied, then analyses based on DNA evidence may indicate a quite distantly related population, albeit one among the more closely related of the existing reference populations. We have added reference population allele frequencies for 14 additional population samples (with >1100 individuals studied) to the 125 population samples previously published for the Kidd Lab 55 AISNP panel. Allele frequencies are now publicly available for all 55 SNPs in ALFRED and FROG-kb for a total of 139 population samples. This Kidd Lab panel of 55 ancestry informative SNPs has been incorporated in commercial kits by both ThermoFisher Scientific and Illumina for massively parallel sequencing. Researchers employing those kits will find the enhanced set of reference populations useful

    Emulsion PCR: A High Efficient Way of PCR Amplification of Random DNA Libraries in Aptamer Selection

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    Aptamers are short RNA or DNA oligonucleotides which can bind with different targets. Typically, they are selected from a large number of random DNA sequence libraries. The main strategy to obtain aptamers is systematic evolution of ligands by exponential enrichment (SELEX). Low efficiency is one of the limitations for conventional PCR amplification of random DNA sequence library in aptamer selection because of relative low products and high by-products formation efficiency. Here, we developed emulsion PCR for aptamer selection. With this method, the by-products formation decreased tremendously to an undetectable level, while the products formation increased significantly. Our results indicated that by-products in conventional PCR amplification were from primer-product and product-product hybridization. In emulsion PCR, we can completely avoid the product-product hybridization and avoid the most of primer-product hybridization if the conditions were optimized. In addition, it also showed that the molecule ratio of template to compartment was crucial to by-product formation efficiency in emulsion PCR amplification. Furthermore, the concentration of the Taq DNA polymerase in the emulsion PCR mixture had a significant impact on product formation efficiency. So, the results of our study indicated that emulsion PCR could improve the efficiency of SELEX

    Validation of a Cost-Efficient Multi-Purpose SNP Panel for Disease Based Research

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    BACKGROUND: Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA "barcoding" to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies. PRINCIPAL FINDINGS: Empirical performance in classification of relative types for any two given DNA samples (e.g., full siblings, parental, etc) indicated that for outbred populations the panel performs sufficiently to classify relationship in extended families and therefore also for smaller structures such as trios and for twin zygosity testing. Additionally, familial relationships do not significantly diminish the (mean match) probability of sharing SNP genotypes in pedigrees, further indicating the uniqueness of the "barcode." Simulation using these SNPs for an African American case-control disease association study demonstrated that population stratification, even in complex admixed samples, can be adequately corrected under a range of disease models using the SNP panel. CONCLUSION: The panel has been validated for use in a variety of human disease genetics research tasks including sample barcoding, relationship verification, population substructure detection and statistical correction. Given the ease of genotyping our specific assay contained herein, this panel represents a useful and economical panel for human geneticists

    Improved Resolution Haplogroup G Phylogeny in the Y Chromosome, Revealed by a Set of Newly Characterized SNPs

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    Background: Y-SNP haplogroup G (hgG), defined by Y-SNP marker M201, is relatively uncommon in the United States general population, with only 8 additional sub-markers characterized. Many of the previously described eight sub-markers are either very rare (2–4%) or do not distinguish between major populations within this hg. In fact, prior to the current study, only 2 % of our reference Caucasian population belonged to hgG and all of these individuals were in sub-haplogroup G2a, defined by P15. Additional Y-SNPs are needed in order to differentiate between individuals within this haplogroup. Principal Findings: In this work we have investigated whether we could differentiate between a population of 63 hgG individuals using previously uncharacterized Y-SNPs. We have designed assays to test these individuals using all known hgG SNPs (n = 9) and an additional 16 unreported/undefined Y-SNPS. Using a combination of DNA sequence and genetic genealogy databases, we have uncovered a total of 15 new hgG SNPs that had been previously reported but not phylogenetically characterized. Ten of the new Y-SNPs are phylogenetically equivalent to M201, one is equivalent to P15 and, interestingly, four create new, separate haplogroups. Three of the latter are more common than many of the previously defined Y-SNPs. Y-STR data from these individuals show that DYS385*12 is present in (70%) of G2a3b1-U13 individuals while only 4 % of non-G2a3b1-U13 individuals posses the DYS385*12 allele. Conclusions: This study uncovered several previously undefined Y-SNPs by using data from several database sources. Th

    Genetic approaches to understanding the causes of stuttering

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    Stuttering is a common but poorly understood speech disorder. Evidence accumulated over the past several decades has indicated that genetic factors are involved, and genetic linkage studies have begun to identify specific chromosomal loci at which causative genes are likely to reside. A detailed investigation of one such region on chromosome 12 has identified mutations in the GNPTAB gene that are associated with stuttering in large families and in the general population. Subsequent studies identified mutations in the functionally related GNPTG and NAGPA genes. Mutations in these genes disrupt the lysosomal targeting pathway that generates the Mannose 6-phosphate signal, which directs a diverse group of enzymes to their target location in the lysosome of the cell. While mutations in these three genes can be identified in less than 10% of cases of familial stuttering, this knowledge allows a variety of new studies that can help identify the neuropathology that underlies this disorder

    Resolving Individuals Contributing Trace Amounts of DNA to Highly Complex Mixtures Using High-Density SNP Genotyping Microarrays

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    We use high-density single nucleotide polymorphism (SNP) genotyping microarrays to demonstrate the ability to accurately and robustly determine whether individuals are in a complex genomic DNA mixture. We first develop a theoretical framework for detecting an individual's presence within a mixture, then show, through simulations, the limits associated with our method, and finally demonstrate experimentally the identification of the presence of genomic DNA of specific individuals within a series of highly complex genomic mixtures, including mixtures where an individual contributes less than 0.1% of the total genomic DNA. These findings shift the perceived utility of SNPs for identifying individual trace contributors within a forensics mixture, and suggest future research efforts into assessing the viability of previously sub-optimal DNA sources due to sample contamination. These findings also suggest that composite statistics across cohorts, such as allele frequency or genotype counts, do not mask identity within genome-wide association studies. The implications of these findings are discussed
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