Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 228
Filtrar
1.
Sci Adv ; 7(6)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33547071

RESUMO

To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.

2.
Genome Biol ; 22(1): 18, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402197

RESUMO

BACKGROUND: Although the genomes of monozygotic twins are practically identical, their methylomes may evolve divergently throughout their lifetime as a consequence of factors such as the environment or aging. Particularly for young and healthy monozygotic twins, DNA methylation divergence, if any, may be restricted to stochastic processes occurring post-twinning during embryonic development and early life. However, to what extent such stochastic mechanisms can systematically provide a stable source of inter-individual epigenetic variation remains uncertain until now. RESULTS: We enriched for inter-individual stochastic variation by using an equivalence testing-based statistical approach on whole blood methylation microarray data from healthy adolescent monozygotic twins. As a result, we identified 333 CpGs displaying similarly large methylation variation between monozygotic co-twins and unrelated individuals. Although their methylation variation surpasses measurement error and is stable in a short timescale, susceptibility to aging is apparent in the long term. Additionally, 46% of these CpGs were replicated in adipose tissue. The identified sites are significantly enriched at the clustered protocadherin loci, known for stochastic methylation in developing neurons. We also confirmed an enrichment in monozygotic twin DNA methylation discordance at these loci in whole genome bisulfite sequencing data from blood and adipose tissue. CONCLUSIONS: We have isolated a component of stochastic methylation variation, distinct from genetic influence, measurement error, and epigenetic drift. Biomarkers enriched in this component may serve in the future as the basis for universal epigenetic fingerprinting, relevant for instance in the discrimination of monozygotic twin individuals in forensic applications, currently impossible with standard DNA profiling.

3.
Forensic Sci Int Genet ; 50: 102412, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33260052

RESUMO

The prediction of appearance traits by use of solely genetic information has become an established approach and a number of statistical prediction models have already been developed for this purpose. However, given limited knowledge on appearance genetics, currently available models are incomplete and do not include all causal genetic variants as predictors. Therefore such prediction models may benefit from the inclusion of additional information that acts as a proxy for this unknown genetic background. Use of priors, possibly informed by trait category prevalence values in biogeographic ancestry groups, in a Bayesian framework may thus improve the prediction accuracy of previously predicted externally visible characteristics, but has not been investigated as of yet. In this study, we assessed the impact of using trait prevalence-informed priors on the prediction performance in Bayesian models for eye, hair and skin color as well as hair structure and freckles in comparison to the respective prior-free models. Those prior-free models were either similarly defined either very close to the already established ones by using a reduced predictive marker set. However, these differences in the number of the predictive markers should not affect significantly our main outcomes. We observed that such priors often had a strong effect on the prediction performance, but to varying degrees between different traits and also different trait categories, with some categories barely showing an effect. While we found potential for improving the prediction accuracy of many of the appearance trait categories tested by using priors, our analyses also showed that misspecification of those prior values often severely diminished the accuracy compared to the respective prior-free approach. This emphasizes the importance of accurate specification of prevalence-informed priors in Bayesian prediction modeling of appearance traits. However, the existing literature knowledge on spatial prevalence is sparse for most appearance traits, including those investigated here. Due to the limitations in appearance trait prevalence knowledge, our results render the use of trait prevalence-informed priors in DNA-based appearance trait prediction currently infeasible.

4.
Forensic Sci Int Genet ; 50: 102395, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33070049

RESUMO

Predicting appearance phenotypes from genotypes is relevant for various areas of human genetic research and applications such as genetic epidemiology, human history, anthropology, and particularly in forensics. Many appearance phenotypes, and thus their underlying genotypes, are highly correlated, with pigmentation traits serving as primary examples. However, all available genetic prediction models, including those for pigmentation traits currently used in forensic DNA phenotyping, ignore phenotype correlations. Here, we investigated the impact of appearance phenotype correlations on genetic appearance prediction in the exemplary case of three pigmentation traits. We used data for categorical eye, hair and skin colour as well as 41 DNA markers utilized in the recently established HIrisPlex-S system from 762 individuals with complete phenotype and genotype information. Based on these data, we performed genetic prediction modelling of eye, hair and skin colour via three different strategies, namely the established approach of predicting phenotypes solely based on genotypes while not considering phenotype correlations, and two novel approaches that considered phenotype correlations, either incorporating truly observed correlated phenotypes or DNA-predicted correlated phenotypes in addition to the DNA predictors. We found that using truly observed correlated pigmentation phenotypes as additional predictors increased the DNA-based prediction accuracies for almost all eye, hair and skin colour categories, with the largest increase for intermediate eye colour, brown hair colour, dark to black skin colour, and particularly for dark skin colour. Outcomes of dedicated computer simulations suggest that this prediction accuracy increase is due to the additional genetic information that is implicitly provided by the truly observed correlated pigmentation phenotypes used, yet not covered by the DNA predictors applied. In contrast, considering DNA-predicted correlated pigmentation phenotypes as additional predictors did not improve the performance of the genetic prediction of eye, hair and skin colour, which was in line with the results from our computer simulations. Hence, in practical applications of DNA-based appearance prediction where no phenotype knowledge is available, such as in forensic DNA phenotyping, it is not advised to use DNA-predicted correlated phenotypes as predictors in addition to the DNA predictors. In the very least, this is not recommended for the pigmentation traits and the established pigmentation DNA predictors tested here.

5.
Clin Epigenetics ; 12(1): 157, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092652

RESUMO

BACKGROUND: Tobacco smoking is a well-known modifiable risk factor for many chronic diseases, including cardiovascular disease (CVD). One of the proposed underlying mechanism linking smoking to disease is via epigenetic modifications, which could affect the expression of disease-associated genes. Here, we conducted a three-way association study to identify the relationship between smoking-related changes in DNA methylation and gene expression and their associations with cardio-metabolic traits. RESULTS: We selected 2549 CpG sites and 443 gene expression probes associated with current versus never smokers, from the largest epigenome-wide association study and transcriptome-wide association study to date. We examined three-way associations, including CpG versus gene expression, cardio-metabolic trait versus CpG, and cardio-metabolic trait versus gene expression, in the Rotterdam study. Subsequently, we replicated our findings in The Cooperative Health Research in the Region of Augsburg (KORA) study. After correction for multiple testing, we identified both cis- and trans-expression quantitative trait methylation (eQTM) associations in blood. Specifically, we found 1224 smoking-related CpGs associated with at least one of the 443 gene expression probes, and 200 smoking-related gene expression probes to be associated with at least one of the 2549 CpGs. Out of these, 109 CpGs and 27 genes were associated with at least one cardio-metabolic trait in the Rotterdam Study. We were able to replicate the associations with cardio-metabolic traits of 26 CpGs and 19 genes in the KORA study. Furthermore, we identified a three-way association of triglycerides with two CpGs and two genes (GZMA; CLDND1), and BMI with six CpGs and two genes (PID1; LRRN3). Finally, our results revealed the mediation effect of cg03636183 (F2RL3), cg06096336 (PSMD1), cg13708645 (KDM2B), and cg17287155 (AHRR) within the association between smoking and LRRN3 expression. CONCLUSIONS: Our study indicates that smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic risk factors. These findings may provide additional insights into the molecular mechanisms linking smoking to the development of CVD.

6.
Genes (Basel) ; 11(6)2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604780

RESUMO

The study of DNA to predict externally visible characteristics (EVCs) and the biogeographical ancestry (BGA) from unknown samples is gaining relevance in forensic genetics. Technical developments in Massively Parallel Sequencing (MPS) enable the simultaneous analysis of hundreds of DNA markers, which improves successful Forensic DNA Phenotyping (FDP). The EU-funded VISAGE (VISible Attributes through GEnomics) Consortium has developed various targeted MPS-based lab tools to apply FDP in routine forensic analyses. Here, we present an evaluation of the VISAGE Basic tool for appearance and ancestry prediction based on PowerSeq chemistry (Promega) on a MiSeq FGx System (Illumina). The panel consists of 153 single nucleotide polymorphisms (SNPs) that provide information about EVCs (41 SNPs for eye, hair and skin color from HIrisPlex-S) and continental BGA (115 SNPs; three overlap with the EVCs SNP set). The assay was evaluated for sensitivity, repeatability and genotyping concordance, as well as its performance with casework-type samples. This targeted MPS assay provided complete genotypes at all 153 SNPs down to 125 pg of input DNA and 99.67% correct genotypes at 50 pg. It was robust in terms of repeatability and concordance and provided useful results with casework-type samples. The results suggest that this MPS assay is a useful tool for basic appearance and ancestry prediction in forensic genetics for users interested in applying PowerSeq chemistry and MiSeq for this purpose.

7.
Forensic Sci Int Genet ; 48: 102336, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32619960

RESUMO

Forensic DNA phenotyping is gaining interest as the number of applications increases within the forensic genetics community. The possibility of providing investigative leads in addition to conventional DNA profiling for human identification provides new insights into otherwise "cold" police investigations. The ability of reporting on the bio-geographical ancestry (BGA), appearance characteristics and age based on DNA obtained from a crime scene sample of an unknown donor makes the exploration of such markers and the development of new methods meaningful for criminal investigations. The VISible Attributes through GEnomics (VISAGE) Consortium aims to disseminate and broaden the use of predictive markers and develop fully optimized and validated prototypes for forensic casework implementation. Here, the first VISAGE appearance and ancestry tool development, performance and validation is reported. A total of 153 SNPs (96.84 % assay conversion rate) were successfully incorporated into a single multiplex reaction using the AmpliSeq™ design pipeline, and applied for massively parallel sequencing with the Ion S5 platform. A collaborative effort involving six VISAGE laboratory partners was devised to perform all validation tests. An extensive validation plan was carefully organized to explore the assay's overall performance with optimum and low-input samples, as well as with challenging and casework mock samples. In addition, forensic validation studies such as concordance and mixture tests recurring to the Coriell sample set with known genotypes were performed. Finally, inhibitor tolerance and specificity were also evaluated. Results showed a robust, highly sensitive assay with good overall concordance between laboratories.

8.
Hum Mutat ; 41(9): 1680-1696, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32579758

RESUMO

Short tandem repeat polymorphisms on the male-specific part of the human Y-chromosome (Y-STRs) are valuable tools in many areas of human genetics. Although their paternal inheritance and moderate mutation rate (~10-3 mutations per marker per meiosis) allow detecting paternal relationships, they typically fail to separate male relatives. Previously, we identified 13 Y-STR markers with untypically high mutation rates (>10-2 ), termed rapidly mutating (RM) Y-STRs, and showed that they improved male relative differentiation over standard Y-STRs. By applying a newly developed in silico search approach to the Y-chromosome reference sequence, we identified 27 novel RM Y-STR candidates. Genotyping them in 1,616 DNA-confirmed father-son pairs for mutation rate estimation empirically highlighted 12 novel RM Y-STRs. Their capacity to differentiate males related by 1, 2, and 3 meioses was 27%, 47%, and 61%, respectively, while for all 25 currently known RM Y-STRs, it was 44%, 69%, and 83%. Of the 647 Y-STR mutations observed in total, almost all were single repeat changes, repeat gains, and losses were well balanced; allele length and fathers' age were positively correlated with mutation rate. We expect these new RM Y-STRs, together with the previously known ones, to significantly improving male relative differentiation in future human genetic applications.

9.
Dtsch Arztebl Int ; 117(15): 269-270, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32449893
10.
Forensic Sci Int Genet ; 47: 102280, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32244163

RESUMO

Human blood traces are amongst the most commonly encountered biological stains collected at crime scenes. Identifying the body site of origin of a forensic blood trace can provide crucial information in many cases, such as in sexual and violent assaults. However, means for reliably and accurately identifying from which body site a forensic blood trace originated are missing, but would be highly valuable in crime scene investigations. With this study, we introduce a taxonomy-independent deep neural network approach based on massively parallel microbiome sequencing, which delivers accurate body site of origin classification of forensically-relevant blood samples, such as menstrual, nasal, fingerprick, and venous blood. A total of 50 deep neural networks were trained using a large 16S rRNA gene sequencing dataset from 773 reference samples, including 220 female urogenital tract, 190 nasal cavity, 213 skin, and 150 venous blood samples. Validation was performed with de-novo generated 16S rRNA gene massively parallel sequencing (MPS) data from 94 blood test samples of four different body sites, and achieved high classification accuracy with AUC values at 0.992 for menstrual blood (N = 23), 0.978 for nasal blood (N = 16), 0.978 for fingerprick blood (N = 30), and 0.990 for venous blood (N = 25). The obtained highly accurate classification of menstrual blood was independent of the day of the menses, as established in additional 86 menstrual blood test samples. Accurate body site of origin classification was also revealed for 45 fresh and aged mock casework blood samples from all four body sites. Our novel microbiome approach works based on the assumption that a sample is from blood, as can be obtained in forensic practise from prior presumptive blood testing, and provides accurate information on the specific body source of blood, with high potentials for future forensic applications.

11.
Forensic Sci Int Genet ; 46: 102266, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32145446

RESUMO

Previous studies suggested that Sudden Infant Death Syndrome (SIDS) can partially be genetically explained by cardiac arrhythmias; however, the number of individuals and populations investigated remain limited. We report the first SIDS study on cardiac arrhythmias genes from the Netherlands, a country with the lowest SIDS incidence likely due to parent education on awareness of environmental risk factors. By using targeted massively parallel sequencing (MPS) in 142 Dutch SIDS cases, we performed a complete exon screening of all 173 exons from 9 cardiac arrhythmias genes SCN5A, KCNQ1, KCNH2, KCNE1, KCNE2, CACNA1C, CAV3, ANK2 and KCNJ2 (∼34,000 base pairs), that were selected to harbour previously established SIDS-associated DNA variants. Motivated by the poor DNA quality from the paraffin embedded material used, the application of a conservative sequencing quality control protocol resulted in 102 SIDS cases surviving quality control. Amongst the 102 SIDS cases, we identified a total of 40 DNA variants in 8 cardiac arrhythmia genes found in 60 (58.8 %) cases. Statistical analyses using ancestry-adjusted reference population data and multiple test correction revealed that 13 (32.5 %) of the identified DNA variants in 6 cardiac arrhythmia genes were significantly associated with SIDS, which were observed in 15 (14.7 %) SIDS cases. These 13, and another three, DNA variants were classified as likely pathogenic for cardiac arrhythmias using the American College of Medical Genetics guidelines for interpretation of sequence variants. The 16 likely pathogenic DNA variants were found in 16 (15.7 %) SIDS cases, including i) 3 novel DNA variants not recorded in public databases ii) 7 known DNA variants for which significant SIDS association established here was previously unknown, and iii) 6 known DNA variants for which LQTS association was reported previously. By having replicated previously reported SIDS-associated DNA variants located in cardiac arrhythmia genes and by having highlighting novel SIDS-associated DNA variants in such genes, our findings provide additional empirical evidence for the partial genetic explanation of SIDS by cardiac arrhythmias. On a wider note, our study outcome stresses the need for routine post-mortem genetic screening of assumed SIDS cases, particularly for cardiac arrhythmia genes. When put in practise, it will allow preventing further sudden deaths (not only in infants) in the affected families, thereby allowing forensic molecular autopsy not only to provide answers on the cause of death, but moreover to save lives.

12.
Eur J Hum Genet ; 28(3): 287-299, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31488894

RESUMO

Previous studies indicated existing, albeit limited, genetic-geographic population substructure in the Dutch population based on genome-wide data and a lack of this for mitochondrial SNP based data. Despite the aforementioned studies, Y-chromosomal SNP data from the Netherlands remain scarce and do not cover the territory of the Netherlands well enough to allow a reliable investigation of genetic-geographic population substructure. Here we provide the first substantial dataset of detailed spatial Y-chromosomal haplogroup information in 2085 males collected across the Netherlands and supplemented with previously published data from northern Belgium. We found Y-chromosomal evidence for genetic-geographic population substructure, and several Y-haplogroups demonstrating significant clinal frequency distributions in different directions. By means of prediction surface maps we could visualize (complex) distribution patterns of individual Y-haplogroups in detail. These results highlight the value of a micro-geographic approach and are of great use for forensic and epidemiological investigations and our understanding of the Dutch population history. Moreover, the previously noted absence of genetic-geographic population substructure in the Netherlands based on mitochondrial DNA in contrast to our Y-chromosome results, hints at different population histories for women and men in the Netherlands.

13.
Eur J Hum Genet ; 28(3): 399, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31645767

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

14.
Elife ; 82019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31763980

RESUMO

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10-8), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (padjusted < 2.1 × 10-3). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.


Assuntos
Face/anatomia & histologia , Loci Gênicos/genética , Desenvolvimento Maxilofacial/genética , Fenótipo , Adolescente , Adulto , Pontos de Referência Anatômicos , Padronização Corporal/genética , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Ontologia Genética , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Adulto Jovem
15.
Forensic Sci Int Genet ; 43: 102152, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31518964

RESUMO

Forensic DNA Phenotyping (FDP) provides the ability to predict externally visible characteristics from minute amounts of crime scene DNA, which can help find unknown perpetrators who are typically unidentifiable via conventional forensic DNA profiling. Fundamental human genetics research has led to a better understanding of the specific DNA variants responsible for physical appearance characteristics, particularly eye, hair, and skin color. Recently, we introduced the HIrisPlex-S system for the simultaneous prediction of eye, hair, and skin color based on 41 DNA variants generated from two forensically validated SNaPshot multiplex assays using capillary electrophoresis (CE). Here we introduce massively parallel sequencing (MPS) solutions for the HIrisPlex-S (HPS) system on two MPS platforms commonly used in forensics, Ion Torrent and MiSeq, that cover all 41 DNA variants in a single assay, respectively. Additionally, we present the forensic developmental validation of the two HPS-MPS assays. The Ion Torrent MPS assay, based on Ion AmpliSeq technology, illustrated the successful generation of full HIrisPlex-S genotypic profiles from 100 pg of input control DNA, while the MiSeq MPS assay based on an in-house design yielded complete profiles from 250 pg of input DNA. Assessing simulated forensic casework samples such as saliva, hair (bulb), blood, semen, and low quantity touch DNA, as well as artificially damaged DNA samples, concordance testing, and samples from numerous species, all illustrated the ability of both versions of the HIrisPlex-S MPS assay to produce results that motivate forensic applications. By also providing an integrated bioinformatics analysis pipeline, MPS data can now be analyzed and a file generated for upload to the publically accessible HIrisPlex online webtool (https://hirisplex.erasmusmc.nl). In addition, we updated the website to accept VCF input data for those with genome sequence data. We thus provide a user-friendly and semi-automated MPS workflow from DNA sample to individual eye, hair, and skin color prediction probabilities. Furthermore, we present a 2-person mixture separation tool that not only assesses genotype reliability with regards genotyping confidence but also provides the most fitting mixture scenario for both minor and major contributors, including profile separation. We envision this MPS implementation of the HIrisPlex-S system for eye, hair, and skin color prediction from DNA as a starting point for further expanding MPS-based forensic DNA phenotyping. This may include the future addition of SNPs predictive for more externally visible characteristics, as well as SNPs for bio-geographic ancestry inference, provided the statistical framework for DNA prediction of these traits is in place.


Assuntos
Cor de Olho/genética , Técnicas de Genotipagem/instrumentação , Cor de Cabelo/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Polimorfismo de Nucleotídeo Único , Pigmentação da Pele/genética , Animais , DNA/genética , Genótipo , Humanos , Fenótipo , Reação em Cadeia da Polimerase , Especificidade da Espécie
16.
Eur J Epidemiol ; 34(11): 1055-1074, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494793

RESUMO

Inferring a person's smoking habit and history from blood is relevant for complementing or replacing self-reports in epidemiological and public health research, and for forensic applications. However, a finite DNA methylation marker set and a validated statistical model based on a large dataset are not yet available. Employing 14 epigenome-wide association studies for marker discovery, and using data from six population-based cohorts (N = 3764) for model building, we identified 13 CpGs most suitable for inferring smoking versus non-smoking status from blood with a cumulative Area Under the Curve (AUC) of 0.901. Internal fivefold cross-validation yielded an average AUC of 0.897 ± 0.137, while external model validation in an independent population-based cohort (N = 1608) achieved an AUC of 0.911. These 13 CpGs also provided accurate inference of current (average AUCcrossvalidation 0.925 ± 0.021, AUCexternalvalidation0.914), former (0.766 ± 0.023, 0.699) and never smoking (0.830 ± 0.019, 0.781) status, allowed inferring pack-years in current smokers (10 pack-years 0.800 ± 0.068, 0.796; 15 pack-years 0.767 ± 0.102, 0.752) and inferring smoking cessation time in former smokers (5 years 0.774 ± 0.024, 0.760; 10 years 0.766 ± 0.033, 0.764; 15 years 0.767 ± 0.020, 0.754). Model application to children revealed highly accurate inference of the true non-smoking status (6 years of age: accuracy 0.994, N = 355; 10 years: 0.994, N = 309), suggesting prenatal and passive smoking exposure having no impact on model applications in adults. The finite set of DNA methylation markers allow accurate inference of smoking habit, with comparable accuracy as plasma cotinine use, and smoking history from blood, which we envision becoming useful in epidemiology and public health research, and in medical and forensic applications.


Assuntos
Cotinina/sangue , Metilação de DNA , DNA/sangue , Epigenômica/métodos , Fumar/efeitos adversos , Adulto , Área Sob a Curva , Biomarcadores/sangue , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fumar/genética , Abandono do Hábito de Fumar
17.
Forensic Sci Int Genet ; 42: 8-13, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31207428

RESUMO

Predicting adult height from DNA has important implications in forensic DNA phenotyping. In 2014, we introduced a prediction model consisting of 180 height-associated SNPs based on data from 10,361 Northwestern Europeans enriched with tall individuals (770 > 1.88 standard deviation), which yielded a mid-ranged accuracy (AUC = 0.75 for binary prediction of tall stature and R2 = 0.12 for quantitative prediction of adult height). Here, we provide an update on DNA-based height predictability considering an enlarged list of subsequently-published height-associated SNPs using data from the same set of 10,361 Europeans. A prediction model based on the full set of 689 SNPs showed an improved accuracy relative to previous models for both tall stature (AUC = 0.79) and quantitative height (R2 = 0.21). A feature selection analysis revealed a subset of 412 most informative SNPs while the corresponding prediction model retained most of the accuracy (AUC = 0.76 and R2 = 0.19) achieved with the full model. Over all, our study empirically exemplifies that the accuracy for predicting human appearance phenotypes with very complex underlying genetic architectures, such as adult height, can be improved by increasing the number of phenotype-associated DNA variants. Our work also demonstrates that a careful sub-selection allows for a considerable reduction of the number of DNA predictors that achieve similar prediction accuracy as provided by the full set. This is forensically relevant due to restrictions in the number of SNPs simultaneously analyzable with forensically suitable DNA technologies in the current days of targeted massively parallel sequencing in forensic genetics.


Assuntos
Estatura/genética , DNA/genética , Grupo com Ancestrais do Continente Europeu/genética , Marcadores Genéticos , Polimorfismo de Nucleotídeo Único , Humanos , Modelos Logísticos , Modelos Genéticos , Fenótipo
19.
Nat Ecol Evol ; 3(6): 986-987, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31068681

RESUMO

In the version of this Article originally published, there were errors in the colour ordering of the legend in Fig. 5b, and in the positions of the target and surrogate populations in Fig. 5c. This has now been corrected. The conclusions of the study are in no way affected. The errors have been corrected in the HTML and PDF versions of the article.

20.
Forensic Sci Int Genet ; 41: 93-106, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063905

RESUMO

Y-chromosomal haplogroups assigned from male-specific Y-chromosomal single nucleotide polymorphisms (Y-SNPs) allow paternal lineage identification and paternal bio-geographic ancestry inference, both being relevant in forensic genetics. However, most previously developed forensic Y-SNP tools did not provide Y haplogroup resolution on the high level needed in forensic applications, because the limited multiplex capacity of the DNA technologies used only allowed the inclusion of a relatively small number of Y-SNPs. In a proof-of-principle study, we recently demonstrated that high-resolution Y haplogrouping is feasible via two AmpliSeq PCR analyses and simultaneous massively parallel sequencing (MPS) of 530 Y-SNPs allowing the inference of 432 Y-haplogroups. With the current study, we present a largely improved Y-SNP MPS lab tool that we specifically designed for the analysis of low quality and quantity DNA often confronted with in forensic DNA analysis. Improvements include i) Y-SNP marker selection based on the "minimal reference phylogeny for the human Y chromosome" (PhyloTree Y), ii) strong increase of the number of targeted Y-SNPs allowing many more Y haplogroups to be inferred, iii) focus on short amplicon length enabling successful analysis of degraded DNA, and iv) combination of all amplicons in a single AmpliSeq PCR and simultaneous sequencing allowing single DNA aliquot use. This new MPS tool simultaneously analyses 859 Y-SNPs and allows inferring 640 Y haplogroups. Preliminary forensic developmental validation testing revealed that this tool performs highly accurate, is sensitive and robust. We also provide a revised software tool for analysing the sequencing data produced by the new MPS lab tool including final Y haplogroup assignment. We envision the tools introduced here for high-resolution Y-chromosomal haplogrouping to determine a man's paternal lineage and/or paternal bio-geographic ancestry to become widely used in forensic Y-chromosome DNA analysis and other applications were Y haplogroup information from low quality / quantity DNA samples is required.


Assuntos
Cromossomos Humanos Y , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , DNA/análise , Degradação Necrótica do DNA , Genética Forense/métodos , Humanos , Masculino , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...