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1.
Genet Epidemiol ; 43(7): 800-814, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31433078

RESUMO

The power of genetic association analyses can be increased by jointly meta-analyzing multiple correlated phenotypes. Here, we develop a meta-analysis framework, Meta-MultiSKAT, that uses summary statistics to test for association between multiple continuous phenotypes and variants in a region of interest. Our approach models the heterogeneity of effects between studies through a kernel matrix and performs a variance component test for association. Using a genotype kernel, our approach can test for rare-variants and the combined effects of both common and rare-variants. To achieve robust power, within Meta-MultiSKAT, we developed fast and accurate omnibus tests combining different models of genetic effects, functional genomic annotations, multiple correlated phenotypes, and heterogeneity across studies. In addition, Meta-MultiSKAT accommodates situations where studies do not share exactly the same set of phenotypes or have differing correlation patterns among the phenotypes. Simulation studies confirm that Meta-MultiSKAT can maintain the type-I error rate at the exome-wide level of 2.5 × 10-6 . Further simulations under different models of association show that Meta-MultiSKAT can improve the power of detection from 23% to 38% on average over single phenotype-based meta-analysis approaches. We demonstrate the utility and improved power of Meta-MultiSKAT in the meta-analyses of four white blood cell subtype traits from the Michigan Genomics Initiative (MGI) and SardiNIA studies.

2.
Genet Epidemiol ; 43(1): 112-117, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30565766

RESUMO

It is unclear whether insertions and deletions (indels) are more likely to influence complex traits than abundant single-nucleotide polymorphisms (SNPs). We sought to understand which category of variation is more likely to impact health. Using the SardiNIA study as an exemplar, we characterized 478,876 common indels and 8,246,244 common SNPs in up to 5,949 well-phenotyped individuals from an isolated valley in Sardinia. We assessed association between 120 traits, resulting in 89 nonoverlapping-associated loci.We evaluated whether indels were enriched among credible sets of potential causal variants. These credible sets included 1,319 SNPs and 88 indels. We did not find indels to be significantly enriched. Indels were the most likely causal variant in seven loci, including one locus associated with monocyte count where an indel with causality and mechanism previously demonstrated (rs200748895:TGCTG/T) had a 0.999 posterior probability. Overall, our results show a very modest and nonsignificant enrichment for common indels in associated loci.


Assuntos
Mutação INDEL/genética , Polimorfismo de Nucleotídeo Único/genética , Loci Gênicos , Humanos , Itália , Anotação de Sequência Molecular
3.
Am J Hum Genet ; 103(5): 691-706, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30388399

RESUMO

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

4.
Nat Genet ; 50(10): 1426-1434, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30224645

RESUMO

The population of the Mediterranean island of Sardinia has made important contributions to genome-wide association studies of complex disease traits and, based on ancient DNA studies of mainland Europe, Sardinia is hypothesized to be a unique refuge for early Neolithic ancestry. To provide new insights on the genetic history of this flagship population, we analyzed 3,514 whole-genome sequenced individuals from Sardinia. Sardinian samples show elevated levels of shared ancestry with Basque individuals, especially samples from the more historically isolated regions of Sardinia. Our analysis also uniquely illuminates how levels of genetic similarity with mainland ancient DNA samples varies subtly across the island. Together, our results indicate that within-island substructure and sex-biased processes have substantially impacted the genetic history of Sardinia. These results give new insight into the demography of ancestral Sardinians and help further the understanding of sharing of disease risk alleles between Sardinia and mainland populations.

5.
BMC Genomics ; 18(1): 747, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28934930

RESUMO

BACKGROUND: We developed a novel software package, XCAVATOR, for the identification of genomic regions involved in copy number variants/alterations (CNVs/CNAs) from short and long reads whole-genome sequencing experiments. RESULTS: By using simulated and real datasets we showed that our tool, based on read count approach, is capable to predict the boundaries and the absolute number of DNA copies CNVs/CNAs with high resolutions. To demonstrate the power of our software we applied it to the analysis Illumina and Pacific Bioscencies data and we compared its performance to other ten state of the art tools. CONCLUSION: All the analyses we performed demonstrate that XCAVATOR is capable to detect germline and somatic CNVs/CNAs outperforming all the other tools we compared. XCAVATOR is freely available at http://sourceforge.net/projects/xcavator/ .


Assuntos
Variações do Número de Cópias de DNA/genética , Técnicas de Genotipagem/métodos , Sequenciamento Completo do Genoma , Polimorfismo de Nucleotídeo Único , Software
6.
Am J Hum Genet ; 100(6): 865-884, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28552196

RESUMO

Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.


Assuntos
Antropometria , Genoma Humano , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas/genética , Análise de Sequência de DNA/métodos , Estatura/genética , Estudos de Coortes , Metilação de DNA/genética , Bases de Dados Genéticas , Feminino , Variação Genética , Humanos , Lipodistrofia/genética , Masculino , Metanálise como Assunto , Obesidade/genética , Mapeamento Físico do Cromossomo , Caracteres Sexuais , Síndrome , Reino Unido
7.
Nat Genet ; 49(5): 700-707, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28394350

RESUMO

Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicing. We identified 21,183 expression quantitative trait loci (eQTLs) and 6,768 splicing quantitative trait loci (sQTLs), including 619 new QTLs. We identified high-frequency QTLs and found evidence of selection near genes involved in malarial resistance and increased multiple sclerosis risk, reflecting the epidemiological history of Sardinia. Using family relationships, we identified 809 segregating expression outliers (median z score of 2.97), averaging 13.3 genes per individual. Outlier genes were enriched for proximal rare variants, providing a new approach to study large-effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.


Assuntos
Perfilação da Expressão Gênica/métodos , Variação Genética , Estudo de Associação Genômica Ampla/métodos , Locos de Características Quantitativas/genética , Processamento Alternativo , Mapeamento Cromossômico , Saúde da Família , Feminino , Predisposição Genética para Doença/genética , Genética Populacional , Genótipo , Humanos , Itália , Masculino , Polimorfismo de Nucleotídeo Único , Sítio de Iniciação de Transcrição
8.
Bioinformatics ; 33(9): 1399-1401, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28453676

RESUMO

Availability and Implementation: fastMitoCalc is available at https://lgsun.irp.nia.nih.gov/hsgu/software/mitoAnalyzer/index.html. Contact: jun.ding@nih.gov. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Dosagem de Genes , Genoma Mitocondrial , Genômica/métodos , Análise de Sequência de DNA/métodos , Software , Genoma Humano , Humanos
9.
N Engl J Med ; 376(17): 1615-1626, 2017 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-28445677

RESUMO

BACKGROUND: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. METHODS: Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. RESULTS: A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. CONCLUSIONS: A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).


Assuntos
Fator Ativador de Células B/genética , Mutação INDEL , Lúpus Eritematoso Sistêmico/genética , Esclerose Múltipla/genética , Autoimunidade , Fator Ativador de Células B/metabolismo , Estudos de Casos e Controles , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Itália , Lúpus Eritematoso Sistêmico/imunologia , MicroRNAs , Esclerose Múltipla/imunologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Risco , Análise de Sequência de RNA , Transcrição Genética
10.
Mol Biol Evol ; 34(5): 1230-1239, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28177087

RESUMO

Sardinians are "outliers" in the European genetic landscape and, according to paleogenomic nuclear data, the closest to early European Neolithic farmers. To learn more about their genetic ancestry, we analyzed 3,491 modern and 21 ancient mitogenomes from Sardinia. We observed that 78.4% of modern mitogenomes cluster into 89 haplogroups that most likely arose in situ. For each Sardinian-specific haplogroup (SSH), we also identified the upstream node in the phylogeny, from which non-Sardinian mitogenomes radiate. This provided minimum and maximum time estimates for the presence of each SSH on the island. In agreement with demographic evidence, almost all SSHs coalesce in the post-Nuragic, Nuragic and Neolithic-Copper Age periods. For some rare SSHs, however, we could not dismiss the possibility that they might have been on the island prior to the Neolithic, a scenario that would be in agreement with archeological evidence of a Mesolithic occupation of Sardinia.


Assuntos
DNA Mitocondrial/genética , Genoma Mitocondrial/genética , DNA Antigo/análise , Demografia , Grupos Étnicos/genética , Grupo com Ancestrais do Continente Europeu/genética , Evolução Molecular , Variação Genética/genética , Genética Populacional/métodos , Haplótipos/genética , Humanos , Ilhas , Itália/etnologia , Filogenia , Análise de Sequência de DNA/métodos
11.
Nat Genet ; 48(10): 1284-1287, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27571263

RESUMO

Genotype imputation is a key component of genetic association studies, where it increases power, facilitates meta-analysis, and aids interpretation of signals. Genotype imputation is computationally demanding and, with current tools, typically requires access to a high-performance computing cluster and to a reference panel of sequenced genomes. Here we describe improvements to imputation machinery that reduce computational requirements by more than an order of magnitude with no loss of accuracy in comparison to standard imputation tools. We also describe a new web-based service for imputation that facilitates access to new reference panels and greatly improves user experience and productivity.


Assuntos
Algoritmos , Genótipo , Simulação por Computador , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Internet
12.
Nat Genet ; 48(10): 1279-83, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27548312

RESUMO

We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.


Assuntos
Genótipo , Haplótipos , Polimorfismo de Nucleotídeo Único , Alelos , Técnicas Genéticas , Estudo de Associação Genômica Ampla , Humanos , Internet , Valores de Referência
13.
Nat Genet ; 47(11): 1352-1356, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26366551

RESUMO

We report sequencing-based whole-genome association analyses to evaluate the impact of rare and founder variants on stature in 6,307 individuals on the island of Sardinia. We identify two variants with large effects. One variant, which introduces a stop codon in the GHR gene, is relatively frequent in Sardinia (0.87% versus <0.01% elsewhere) and in the homozygous state causes Laron syndrome involving short stature. We find that this variant reduces height in heterozygotes by an average of 4.2 cm (-0.64 s.d.). The other variant, in the imprinted KCNQ1 gene (minor allele frequency (MAF) = 7.7% in Sardinia versus <1% elsewhere) reduces height by an average of 1.83 cm (-0.31 s.d.) when maternally inherited. Additionally, polygenic scores indicate that known height-decreasing alleles are at systematically higher frequencies in Sardinians than would be expected by genetic drift. The findings are consistent with selection for shorter stature in Sardinia and a suggestive human example of the proposed 'island effect' reducing the size of large mammals.


Assuntos
Estatura/genética , Variação Genética , Síndrome de Laron/genética , Seleção Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte/genética , Feminino , Efeito Fundador , Frequência do Gene , Estudo de Associação Genômica Ampla/métodos , Genótipo , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Ilhas , Itália , Canal de Potássio KCNQ1/genética , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Nat Genet ; 47(11): 1264-71, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26366553

RESUMO

We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.


Assuntos
Genoma Humano/genética , Estudo de Associação Genômica Ampla/métodos , Técnicas de Genotipagem/métodos , Hemoglobinas/genética , Análise de Sequência de DNA/métodos , Adulto , Feminino , Variação Genética , Genótipo , Humanos , Ilhas , Itália , Masculino , Pessoa de Meia-Idade , Família Multigênica , Polimorfismo de Nucleotídeo Único , alfa-Globinas/genética , Globinas beta/genética
15.
Nat Genet ; 47(11): 1272-1281, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26366554

RESUMO

We report ∼17.6 million genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from previous sequencing-based compilations and are enriched for predicted functional consequences. Furthermore, ∼76,000 variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. We observe 14 signals, including 2 major new loci, for lipid levels and 19 signals, including 2 new loci, for inflammatory markers. The new associations would have been missed in analyses based on 1000 Genomes Project data, underlining the advantages of large-scale sequencing in this founder population.


Assuntos
Biomarcadores/sangue , Variação Genética , Genoma Humano/genética , Estudo de Associação Genômica Ampla/métodos , Lipídeos/sangue , Análise de Sequência de DNA/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Efeito Fundador , Frequência do Gene , Genética Populacional , Genótipo , Geografia , Haplótipos , Humanos , Mediadores da Inflamação/sangue , Itália , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
17.
PLoS Genet ; 11(7): e1005306, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26172475

RESUMO

DNA sequencing identifies common and rare genetic variants for association studies, but studies typically focus on variants in nuclear DNA and ignore the mitochondrial genome. In fact, analyzing variants in mitochondrial DNA (mtDNA) sequences presents special problems, which we resolve here with a general solution for the analysis of mtDNA in next-generation sequencing studies. The new program package comprises 1) an algorithm designed to identify mtDNA variants (i.e., homoplasmies and heteroplasmies), incorporating sequencing error rates at each base in a likelihood calculation and allowing allele fractions at a variant site to differ across individuals; and 2) an estimation of mtDNA copy number in a cell directly from whole-genome sequencing data. We also apply the methods to DNA sequence from lymphocytes of ~2,000 SardiNIA Project participants. As expected, mothers and offspring share all homoplasmies but a lesser proportion of heteroplasmies. Both homoplasmies and heteroplasmies show 5-fold higher transition/transversion ratios than variants in nuclear DNA. Also, heteroplasmy increases with age, though on average only ~1 heteroplasmy reaches the 4% level between ages 20 and 90. In addition, we find that mtDNA copy number averages ~110 copies/lymphocyte and is ~54% heritable, implying substantial genetic regulation of the level of mtDNA. Copy numbers also decrease modestly but significantly with age, and females on average have significantly more copies than males. The mtDNA copy numbers are significantly associated with waist circumference (p-value = 0.0031) and waist-hip ratio (p-value = 2.4×10-5), but not with body mass index, indicating an association with central fat distribution. To our knowledge, this is the largest population analysis to date of mtDNA dynamics, revealing the age-imposed increase in heteroplasmy, the relatively high heritability of copy number, and the association of copy number with metabolic traits.


Assuntos
Variações do Número de Cópias de DNA/genética , DNA Mitocondrial/genética , Dosagem de Genes/genética , Linfócitos/citologia , Obesidade/genética , Envelhecimento , Algoritmos , Sequência de Bases , Distribuição da Gordura Corporal , Índice de Massa Corporal , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Análise de Sequência de DNA , Fatores Sexuais , Circunferência da Cintura/genética , Relação Cintura-Quadril
18.
BMC Res Notes ; 8: 174, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-25926048

RESUMO

BACKGROUND: Next-Generation Sequencing methods have led to a great increase in phylogenetically useful markers within the male specific portion of the Y chromosome, but previous studies have limited themselves to the study of the X-degenerate regions. METHODS: DNA was extracted from peripheral blood samples of adult males whose paternal grandfathers were born in Sardinia. The DNA samples were sequenced, genotyped and subsequently analysed for variant calling for approximately 23.1 Mbp of the Y chromosome. A phylogenetic tree was built using Network 4.6 software. RESULTS: From low coverage whole genome sequencing of 1,194 Sardinian males, we extracted 20,155 phylogenetically informative single nucleotide polymorphisms from the whole euchromatic region, including the X-degenerate, X-transposed, and Ampliconic regions, along with variants in other unclassified chromosome intervals and in the readable sequences of the heterochromatic region. CONCLUSIONS: The non X-degenerate classes contain a significant portion of the phylogenetic variation of the whole chromosome and their inclusion in the analysis, almost doubling the number of informative polymorphisms, refining the known molecular phylogeny of the human Y chromosome.


Assuntos
Cromossomos Humanos Y/genética , Filogenia , Polimorfismo de Nucleotídeo Único/genética , Adulto , Geografia , Haplótipos/genética , Humanos , Itália , Masculino
19.
Eur J Hum Genet ; 23(7): 975-83, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25293720

RESUMO

The utility of genotype imputation in genome-wide association studies is increasing as progressively larger reference panels are improved and expanded through whole-genome sequencing. Developing general guidelines for optimally cost-effective imputation, however, requires evaluation of performance issues that include the relative utility of study-specific compared with general/multipopulation reference panels; genotyping with various array scaffolds; effects of different ethnic backgrounds; and assessment of ranges of allele frequencies. Here we compared the effectiveness of study-specific reference panels to the commonly used 1000 Genomes Project (1000G) reference panels in the isolated Sardinian population and in cohorts of European ancestry including samples from Minnesota (USA). We also examined different combinations of genome-wide and custom arrays for baseline genotypes. In Sardinians, the study-specific reference panel provided better coverage and genotype imputation accuracy than the 1000G panels and other large European panels. In fact, even gene-centered custom arrays (interrogating ~200 000 variants) provided highly informative content across the entire genome. Gain in accuracy was also observed for Minnesotans using the study-specific reference panel, although the increase was smaller than in Sardinians, especially for rare variants. Notably, a combined panel including both study-specific and 1000G reference panels improved imputation accuracy only in the Minnesota sample, and only at rare sites. Finally, we found that when imputation is performed with a study-specific reference panel, cutoffs different from the standard thresholds of MACH-Rsq and IMPUTE-INFO metrics should be used to efficiently filter badly imputed rare variants. This study thus provides general guidelines for researchers planning large-scale genetic studies.


Assuntos
Genoma Humano/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Análise Custo-Benefício , Grupo com Ancestrais do Continente Europeu/genética , Frequência do Gene , Genética Populacional , Estudo de Associação Genômica Ampla/economia , Genótipo , Haplótipos , Humanos , Itália , Minnesota , Projetos de Pesquisa , Análise de Sequência de DNA/economia
20.
PLoS Genet ; 10(5): e1004353, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24809476

RESUMO

Genome sequencing of the 5,300-year-old mummy of the Tyrolean Iceman, found in 1991 on a glacier near the border of Italy and Austria, has yielded new insights into his origin and relationship to modern European populations. A key finding of that study was an apparent recent common ancestry with individuals from Sardinia, based largely on the Y chromosome haplogroup and common autosomal SNP variation. Here, we compiled and analyzed genomic datasets from both modern and ancient Europeans, including genome sequence data from over 400 Sardinians and two ancient Thracians from Bulgaria, to investigate this result in greater detail and determine its implications for the genetic structure of Neolithic Europe. Using whole-genome sequencing data, we confirm that the Iceman is, indeed, most closely related to Sardinians. Furthermore, we show that this relationship extends to other individuals from cultural contexts associated with the spread of agriculture during the Neolithic transition, in contrast to individuals from a hunter-gatherer context. We hypothesize that this genetic affinity of ancient samples from different parts of Europe with Sardinians represents a common genetic component that was geographically widespread across Europe during the Neolithic, likely related to migrations and population expansions associated with the spread of agriculture.


Assuntos
Fósseis , Genética Populacional , Genoma Humano , Europa (Continente) , Feminino , Humanos , Polimorfismo de Nucleotídeo Único
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