scholarly journals TranslucentID: Detecting Individuals with High Confidence in Saturated DNA SNP Mixtures

2018 ◽  
Author(s):  
Darrell O. Ricke ◽  
James Watkins ◽  
Philip Fremont-Smith ◽  
Tara Boettcher ◽  
Eric Schwoebel
Keyword(s):  
High Throughput Sequencing ◽  
Nucleotide Polymorphisms ◽  
Forensic Dna ◽  
Mixture Analysis ◽  
High Confidence ◽  
Dna Mixtures ◽  
Single Nucleotide ◽  
Minor Alleles ◽  
Dna Mixture ◽  
Mixture Samples

AbstractHigh throughput sequencing (HTS) of complex DNA mixtures with single nucleotide polymorphisms (SNPs) panels can identify multiple individuals in forensic DNA mixture samples. SNP mixture analysis relies upon the exclusion of non-contributing individuals with the subset of SNP loci with no detected minor alleles in the mixture. Few, if any, individuals are anticipated to be detectable in saturated mixtures by this mixture analysis approach because of the increased probability of matching random individuals. Being able to identify a subset of the contributors in saturated HTS SNP mixtures is valuable for forensic investigations. A desaturated mixture can be created by treating a set of SNPs with the lowest minor allele ratios as having no minor alleles. Leveraging differences in DNA contributor concentrations in saturated mixtures, we introduce TranslucentID for the identification of a subset of individuals with high confidence who contributed DNA to saturated mixtures by desaturating the mixtures.

scholarly journals The Plateau Method for Forensic DNA SNP Mixture Deconvolution

2017 ◽  
Author(s):  
Darrell O. Ricke ◽  
Joe Isaacson ◽  
James Watkins ◽  
Philip Fremont-Smith ◽  
Tara Boettcher ◽  
...  
Keyword(s):  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
High Throughput Sequencing ◽  
Nucleotide Polymorphisms ◽  
Forensic Dna ◽  
Dna Mixtures ◽  
Single Nucleotide ◽  
Mixture Deconvolution ◽  
Dna Mixture ◽  
Short Tandem

AbstractIdentification of individuals in complex DNA mixtures remains a challenge for forensic analysts. Recent advances in high throughput sequencing (HTS) are enabling analysis of DNA mixtures with expanded panels of Short Tandem Repeats (STRs) and/or Single Nucleotide Polymorphisms (SNPs). We present the plateau method for direct SNP DNA mixture deconvolution into sub-profiles based on differences in contributors’ DNA concentrations in the mixtures in the absence of matching reference profiles. The Plateau method can detect profiles of individuals whose contribution is as low as 1/200 in a DNA mixture (patent pending)1.

scholarly journals 11 Million SNP Reference Profiles for Identity Searching Across Ethnicities, Kinship, and Admixture

2018 ◽  
Author(s):  
Brian S. Helfer ◽  
Darrell O. Ricke
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
High Throughput ◽  
Family Relationships ◽  
In Silico ◽  
High Throughput Sequencing ◽  
Genetic Data ◽  
Nucleotide Polymorphisms ◽  
Mixture Analysis ◽  
Single Nucleotide ◽  
Public Repositories

AbstractHigh throughput sequencing (HTS) of single nucleotide polymorphisms (SNPs) provides additional applications for DNA forensics including identification, mixture analysis, kinship prediction, and biogeographic ancestry prediction. Public repositories of human genetic data are being rapidly generated and released, but the majorities of these samples are de-identified to protect privacy, and have little or no individual metadata such as appearance (photos), ethnicity, relatives, etc. A reference in silico dataset has been generated to enable development and testing of new DNA forensics algorithms. This dataset provides 11 million SNP profiles for individuals with defined ethnicities and family relationships spanning eight generations with admixture for a panel with 39,108 SNPs.

scholarly journals The Glucocorticoid Receptor Polymorphism Landscape in Patients With Diamond Blackfan Anemia Reveals an Association Between Two Clinically Relevant Single Nucleotide Polymorphisms and Time to Diagnosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Annalisa Lonetti ◽  
Valentina Indio ◽  
Irma Dianzani ◽  
Ugo Ramenghi ◽  
Lydie Da Costa ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Glucocorticoid Receptor ◽  
Compensatory Mechanism ◽  
Nucleotide Polymorphisms ◽  
Disease Manifestation ◽  
Single Nucleotide ◽  
Diamond Blackfan Anemia ◽  
Glucocorticoid Response ◽  
Minor Alleles ◽  
Population Demographic

NR3C1, the gene encoding the glucocorticoid receptor, is polymorphic presenting numerous single nucleotide polymorphisms (SNPs) some of which are emerging as leading cause in the variability of manifestation and/or response to glucocorticoids in human diseases. Since 60–80% of patients with Diamond Blackfan anemia (DBA), an inherited pure red cell aplasia induced by mutations in ribosomal protein genes became transfusion independent upon treatment with glucocorticoids, we investigated whether clinically relevant NR3C1 SNPs are associated with disease manifestation in DBA. The eight SNPs rs10482605, rs10482616, rs7701443, rs6189/rs6190, rs860457, rs6198, rs6196, and rs33388/rs33389 were investigated in a cohort of 91 European DBA patients. Results were compared with those observed in healthy volunteers (n=37) or present in public genome databases of Italian and European populations. Although, cases vs. control analyses suggest that the frequency of some of the minor alleles is significantly altered in DBA patients with respect to healthy controls or to the Italian or other European registries, lack of consistency among the associations across different sets suggests that overall the frequency of these SNPs in DBA is not different from that of the general population. Demographic data (47 females and 31 males) and driver mutations (44 S and 29 L genes and eight no-known mutation) are known for 81 patients while glucocorticoid response is known, respectively, for 81 (36 responsive and 45 non-responsive) and age of disease onsets for 79 (55 before and 24 after 4months of age) patients. Neither gender nor leading mutations were associated with the minor alleles or with disease manifestation. In addition, none of the SNPs met the threshold in the response vs. non-responsive groups. However, two SNPs (rs6196 and rs860457) were enriched in patients manifesting the disease before 4months of age. Although the exact biomechanistical consequences of these SNPs are unknown, the fact that their configuration is consistent with that of regulatory regions suggests that they regulate changes in glucocorticoid response during ontogeny. This hypothesis was supported by phosphoproteomic profiling of erythroid cells expanded ex vivo indicating that glucocorticoids activate a ribosomal signature in cells from cord blood but not in those from adult blood, possibly providing a compensatory mechanism to the driving mutations observed in DBA before birth.

scholarly journals Investigation of Genetic Relationships within Miscanthus using SNP Markers Identified using SLAF-Seq

2021 ◽  
Author(s):  
ZHIYONG Chen ◽  
Yancen He ◽  
Yasir Iqbal ◽  
Yanlan Shi ◽  
Hongmei Huang ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Genetic Relationships ◽  
Female Parent ◽  
Snp Markers ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Breeding Programs ◽  
Sequencing Method ◽  
Specific Locus

Abstract Background: Miscanthus, which is a leading dedicated-energy grass in Europe and in parts of Asia, is expected to play a key role in the development of the future bioeconomy. However, due to its complex genetic background, it is difficult to investigate phylogenetic relationships and the evolution of gene function in this genus. Here, we investigated 50 Miscanthus germplasms: 1 female parent (M. lutarioriparius), 30 candidate male parents (M. lutarioriparius, M. sinensis, and M. sacchariflorus), and 19 offspring. We used high-throughput Specific-Locus Amplified Fragment sequencing (SLAF-seq) to identify informative single nucleotide polymorphisms (SNPs) in all germplasms.Results: We identified 800,081 SLAF tags, of which 160,368 were polymorphic. Each tag was 264–364 bp long. The obtained SNPs were used to investigate genetic relationships within Miscanthus. We constructed a phylogenetic tree of the 50 germplasms using the obtained SNPs, and found that the germplasms fell into two clades: one clade of M. sinensis only and one clade that included the offspring, M. lutarioriparius, and M. sacchariflorus. Genetic cluster analysis indicated that M. lutarioriparius germplasm C3 was the most likely male parent of the offspring.Conclusions: As a high-throughput sequencing method, SLAF-seq can be used to identify informative SNPs in Miscanthus germplasms and to rapidly characterize genetic relationships within this genus. Our results will support the development of breeding programs utilizing Miscanthus cultivars with elite biomass- or fiber-production potential.

scholarly journals Effect of single-nucleotide polymorphisms on the breeding value of fertility and breeding value of beef in Hungarian Simmental cattle

2018 ◽  
Vol 66 (2) ◽  
pp. 215-225 ◽  
Author(s):  
István Anton ◽  
Balázs Húth ◽  
Imre Füller ◽  
György Gábor ◽  
Gabriella Holló ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Mixed Model ◽  
Breeding Value ◽  
Nucleotide Polymorphisms ◽  
Molecular Tools ◽  
Single Nucleotide ◽  
Chip Data ◽  
Minor Alleles ◽  
Simmental Cattle ◽  
Data Screening

The objective of this study was to estimate the effect of single-nucleotide polymorphisms (SNPs) on the breeding value of fertility (BVF) and the breeding value of beef (BVB) in Hungarian Simmental cattle. Genotypes were determined on a high-density Illumina Bovine DNA Chip. Data screening and data identification were performed by multi-locus mixed-model. Statistical analyses were carried out to find associations between individual genotypes and the investigated quality values. Three loci showed considerable association with BVF (–log10 P = 9.5, 9.9 and 14.5, respectively) on chromosomes 9, 28 and 29, respectively. The frequencies of their minor alleles (MAF) were 0.375, 0.355 and 0.354, respectively. Two loci showed association with BVB (–log10 P = 25.3 and 22.7) on chromosomes 2 and 11, respectively (their MAF were 0.438 and 0.229). The abovementioned loci provide a straightforward possibility to assist selection by molecular tools.

scholarly journals Associations of Polymorphisms in the Apolipoprotein APOA1-C3-A5 Gene Cluster with Acute Coronary Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Yan Ding ◽  
Ming An Zhu ◽  
Zhi Xiao Wang ◽  
Jing Zhu ◽  
Jing Bo Feng ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Acute Coronary Syndromes ◽  
Lipid Homeostasis ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Coronary Syndrome ◽  
Minor Alleles ◽  
Coronary Syndromes

Background. Acute coronary syndromes (ACSs) are clinically cardiovascular events associated with dyslipidemia in common. Single nucleotide polymorphisms (SNPs) and haplotypes in the APOA1/C3/A5 gene cluster are associated with diabetes and familial combined hyperlipidaemia (FCH). Little is known about whether the polymorphisms in these genes affect lipid homeostasis in patients with ACSs. The present paper aimed to examine these associations with 4 SNPs in the APOA1 −75G>A, the APOC3 −455T>C, and APOA5 −1131T>C, c.553G>Tvariant to ACSs in Chinese Han.Methods. Chinese Han of 229 patients with ACSs and 254 unrelated controls were analyzed. Four SNPs in APOA1/C3/A5 cluster were genotyped and lipid was determined.Results. Our data show that minor allelic frequencies of APOC3 −455T>C, APOA5 −1131T>C, and c.553G>Tpolymorphisms in patients with ACSs were significantly higher than control group (P<0.05). Furthermore, the 3 polymorphic sites were strongly of linkage disequilibrium, and minor alleles of 3 SNP sites had higher TG level than wild alleles (P<0.05), APOC3 −455C and APOA5 c.553T allele carriers also had lower level of HDL-C.Conclusions. The minor alleles of APOC3 −455T>C, APOA5 −1131T>C, and c.553G>Tpolymorphisms are closely associated with ACSs.

scholarly journals Fast P(RMNE): Fast Forensic DNA Probability of Random Man Not Excluded Calculation

2017 ◽  
Author(s):  
Darrell O. Ricke ◽  
Steven Schwartz
Keyword(s):  
Tandem Repeats ◽  
High Throughput Sequencing ◽  
Massively Parallel Sequencing ◽  
Computation Time ◽  
Data Sets ◽  
Computationally Efficient ◽  
Forensic Dna ◽  
Dna Index ◽  
Dna Mixture ◽  
New Formula

AbstractHigh throughput sequencing (HTS) of DNA forensic samples is expanding from the sizing of short tandem repeats (STRs) to massively parallel sequencing (MPS). HTS panels are expanding from the FBI 20 core Combined DNA Index System (CODIS) loci to include SNPs. The calculation of random man not excluded, P(RMNE), is used in DNA mixture analysis to estimate the probability that a person is present in a DNA mixture. This calculation encounters calculation artifacts with expansion to larger panel sizes. Increasing the floating-point precision of the calculations allows for increased panel sizes but with a corresponding increase in computation time. The Taylor series higher precision libraries used fail on some input data sets leading to algorithm unreliability. Herein, a new formula is introduced for calculating P(RMNE) that scales to larger SNP panel sizes while being computationally efficient (patent pending)[1].

scholarly journals Re-Identification of Individuals in Genomic Data-Sharing Beacons via Allele Inference

2017 ◽  
Author(s):  
Nora von Thenen ◽  
Erman Ayday ◽  
A. Ercument Cicek
Keyword(s):  
Data Sharing ◽  
Genomic Data ◽  
Nucleotide Polymorphisms ◽  
Privacy Risk ◽  
High Confidence ◽  
Single Nucleotide ◽  
Order Markov Chain ◽  
Adversary Model ◽  
Very High ◽  
Membership Information

AbstractGenomic datasets are often associated with sensitive phenotypes. Therefore, the leak of membership information is a major privacy risk. Genomic beacons aim to provide a secure, easy to implement, and standardized interface for data sharing by only allowing yes/no queries on the presence of specific alleles in the dataset. Previously deemed secure against re-identification attacks, beacons were shown to be vulnerable despite their stringent policy. Recent studies have demonstrated that it is possible to determine whether the victim is in the dataset, by repeatedly querying the beacon for his/her single nucleotide polymorphisms (SNPs). In this work, we propose a novel re-identification attack and show that the privacy risk is more serious than previously thought. Using the proposed attack, even if the victim systematically hides informative SNPs (i.e., SNPs with very low minor allele frequency -MAF-), it is possible to infer the alleles at positions of interest as well as the beacon query results with very high confidence. Our method is based on the fact that alleles at different loci are not necessarily independent. We use the linkage disequilibrium and a high-order Markov chain-based algorithm for the inference. We show that in a simulated beacon with 65 individuals from the CEU population, we can infer membership of individuals with 95% confidence with only 5 queries, even when SNPs with MAF less than 0.05 are hidden. This means, we need less than 0.5% of the number of queries that existing works require, to determine beacon membership under the same conditions. We further show that countermeasures such as hiding certain parts of the genome or setting a query budget for the user would fail to protect the privacy of the participants under our adversary model.

Computational detection, analysis and interpretations of genomic variants in human diseases associated GENEMDM 2

2021 ◽  
Vol 7 (2) ◽  
pp. 141-154
Keyword(s):  
Computational Methods ◽  
High Throughput Sequencing ◽  
Cancer Susceptibility ◽  
In Silico Analysis ◽  
Human Diseases ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide Variants ◽  
Mdm2 Gene ◽  
Single Nucleotide ◽  
Computational Tools

Most of the mutations described in human MDM2 are tolerated without significantly disrupting the corresponding structural or molecular function. However, some of them are associated with a variety of human diseases, including cancer. Numerous computational methods have been developed to predict the effects of missense single nucleotide variants (SNVs). The non-synonymous single nucleotide polymorphisms affect the function of XRCC1, which impairs the ability to repair DNA and therefore increases the risk of diseases such as cancer. In this study, sequence and structure-based computational tools were used to screen the total listed coding SNPs of the MDM2 gene in order to recognize and describe them. The potential 6 ns SNP of MDM2 were identified from 29 ns SNP by consistent analysis using computational tools PolyPhen 2, SIFT, PANTHER and cSNP. The computational methods were used to systematically classify functional mutations in the regulatory and coding regions that modify the expression and function of the MDM2 enzyme. The HOPE project also made it possible to elaborate the structural effects of the substitutions of amino acids. In silico analysis predicted that rs759244097 is harmful. This study concluded that identifying this SNP will help to determine an individual's cancer susceptibility, prognosis and further treatment. Furthermore, current high-throughput sequencing efforts and the need for extensive interpretation of protein sequence variants requires more efficient and accurate computational methods in the coming years.

Single Nucleotide Polymorphisms in Carnosinase Genes (CNDP1 and CNDP2) are Associated With Power Athletic Status

2017 ◽  
Vol 27 (6) ◽  
pp. 533-542 ◽  
Author(s):  
João Paulo Limongi França Guilherme ◽  
Antonio Herbert Lancha
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Endurance Athletes ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Athletic Status ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
Minor Alleles ◽  
Representative Cohort

Carnosine (β-alanyl-L-histidine), abundantly found in skeletal muscle, plays an important role during exercise, especially for high-intensity contractions. Variability in muscle carnosine content between individuals exists and may also be explained by different genetic bases, although no study has addressed the association of polymorphisms in genes related to carnosine metabolism in athletes. This study aimed to investigate the frequency of single nucleotide polymorphisms (SNPs) in the carnosinase genes (CNDP1 and CNDP2) in a large Brazilian cohort of athletes and nonathletes. Eight SNPs were compared between a representative cohort of elite athletes from Brazil (n = 908) and a paired group of nonathletes (n = 967). The athletes were stratified into three groups: endurance (n = 328), power (n = 415), and combat (n = 165). The CNDP2 rs6566810 (A/A genotype) is overrepresented in endurance athletes, but only in international-level endurance athletes. Three SNPs (CNDP2 rs3764509, CNDP2-CNDP1 rs2346061, and CNDP1 rs2887) were overrepresented in power athletes compared with nonathletes. Carriers of the minor allele had an increased odds ratio of being a power athlete. For the rs2346061, no significant difference was observed in genotype frequencies between power and combat sports athletes, but for rs2887 the power and combat groups showed an inverse genotype distribution. In conclusion, we found that minor alleles carriers for CNDP2 rs3764509 (G-allele), CNDP2-CNDP1 rs2346061 (C-allele), and CNDP1 rs2887 (A-allele) are more likely to be a power athlete. These polymorphisms may be novel genetic markers for power athletes. Furthermore, these results are suggestive of a distinct CNDP genotype for sporting development.

Sign in / Sign up

Export Citation Format

Share Document