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1.
BMC Genomics ; 22(1): 442, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118867

RESUMO

BACKGROUND: Rutabaga or swede (Brassica napus ssp. napobrassica (L.) Hanelt) varies in root and leaf shape and colour, flesh colour, foliage growth habits, maturity date, seed quality parameters, disease resistance and other traits. Despite these morphological differences, no in-depth molecular analyses of genetic diversity have been conducted in this crop. Understanding this diversity is important for conservation and broadening the use of this resource. RESULTS: This study investigated the genetic diversity within and among 124 rutabaga accessions from five Nordic countries (Norway, Sweden, Finland, Denmark and Iceland) using a 15 K single nucleotide polymorphism (SNP) Brassica array. After excluding markers that did not amplify genomic DNA, monomorphic and low coverage site markers, the accessions were analyzedwith 6861 SNP markers. Allelic frequency statistics, including polymorphism information content (PIC), minor allele frequency (MAF) and mean expected heterozygosity ([Formula: see text]e) and population differentiation statistics such as Wright's F-statistics (FST) and analysis of molecular variance (AMOVA) indicated that the rutabaga accessions from Norway, Sweden, Finland and Denmark were not genetically different from each other. In contrast, accessions from these countries were significantly different from the accessions from Iceland (P < 0.05). Bayesian analysis with the software STRUCTURE placed 66.9% of the rutabaga accessions into three to four clusters, while the remaining 33.1% constituted admixtures. Three multivariate analyses: principal coordinate analysis (PCoA), the unweighted pair group method with arithmetic mean (UPGMA) and neighbour-joining (NJ) clustering methods grouped the 124 accessions into four to six subgroups. CONCLUSION: Overall, the correlation of the accessions with their geographic origin was very low, except for the accessions from Iceland. Thus, Icelandic rutabaga accessions can offer valuable germplasm for crop improvement.


Assuntos
Brassica napus , Genética Populacional , Polimorfismo de Nucleotídeo Único , Teorema de Bayes , Brassica napus/genética , Dinamarca , Finlândia , Variação Genética , Islândia , Biologia Molecular , Noruega , Suécia
2.
An Acad Bras Cienc ; 93(2): e20200452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076039

RESUMO

Microsatellite primers pairs were developed for the Neotropical tree Roupala montana var. brasiliensis for use in studies on genetic diversity, mating system, and gene flow. Forty-two primer pairs were developed, resulting in 27 polymorphic loci, with two to 27 alleles per locus. The primer pairs were validated against 34 R. montana var. brasiliensis adult trees from four populations. The observed (H o) and expected (H e)heterozygosities ranged among loci from 0.061 to 0.930 (mean of 0.544) and from 0.116 to 0.950 (mean of 0.700), respectively. Null alleles were observed for ten loci. No genotypic linkage disequilibrium was detected in any pair of loci. This set of loci is suitable for population genetic studies of the species.


Assuntos
Repetições de Microssatélites , Proteaceae/genética , Genética Populacional , Genótipo , Polimorfismo Genético
3.
BMC Genomics ; 22(1): 388, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039278

RESUMO

BACKGROUND: Elucidating the effects of geography and selection on genetic variation is critical for understanding the relative importance of adaptation in driving differentiation and identifying the environmental factors underlying its occurrence. Adaptive genetic variation is common in tree species, especially widely distributed long-lived species. Pseudotaxus chienii can occupy diverse habitats with environmental heterogeneity and thus provides an ideal material for investigating the process of population adaptive evolution. Here, we characterize genetic and expression variation patterns and investigate adaptive genetic variation in P. chienii populations. RESULTS: We generated population transcriptome data and identified 13,545 single nucleotide polymorphisms (SNPs) in 5037 unigenes across 108 individuals from 10 populations. We observed lower nucleotide diversity (π = 0.000701) among the 10 populations than observed in other gymnosperms. Significant negative correlations between expression diversity and nucleotide diversity in eight populations suggest that when the species adapts to the surrounding environment, gene expression and nucleotide diversity have a reciprocal relationship. Genetic structure analyses indicated that each distribution region contains a distinct genetic group, with high genetic differentiation among them due to geographical isolation and local adaptation. We used FST outlier, redundancy analysis, and latent factor mixed model methods to detect molecular signatures of local adaptation. We identified 244 associations between 164 outlier SNPs and 17 environmental variables. The mean temperature of the coldest quarter, soil Fe and Cu contents, precipitation of the driest month, and altitude were identified as the most important determinants of adaptive genetic variation. Most candidate unigenes with outlier signatures were related to abiotic and biotic stress responses, and the monoterpenoid biosynthesis and ubiquitin-mediated proteolysis KEGG pathways were significantly enriched in certain populations and deserve further attention in other long-lived trees. CONCLUSIONS: Despite the strong population structure in P. chienii, genomic data revealed signatures of divergent selection associated with environmental variables. Our research provides SNPs, candidate unigenes, and biological pathways related to environmental variables to facilitate elucidation of the genetic variation in P. chienii in relation to environmental adaptation. Our study provides a promising tool for population genomic analyses and insights into the molecular basis of local adaptation.


Assuntos
Taxaceae , Transcriptoma , Adaptação Fisiológica/genética , Biologia Computacional , Deriva Genética , Genética Populacional , Humanos , Polimorfismo de Nucleotídeo Único
4.
Nat Commun ; 12(1): 2684, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976138

RESUMO

Shigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring the spread of resistant clones, including those that have recently emerged, at local and global scales.


Assuntos
Disenteria Bacilar/diagnóstico , Genoma Bacteriano/genética , Genômica/métodos , Shigella sonnei/genética , Antibacterianos/farmacologia , Austrália , Azitromicina/farmacologia , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Disenteria Bacilar/microbiologia , Inglaterra , Genética Populacional , Genótipo , Geografia , Saúde Global , Humanos , Testes de Sensibilidade Microbiana/métodos , Filogenia , Polimorfismo de Nucleotídeo Único , Shigella sonnei/classificação , Shigella sonnei/fisiologia , Estados Unidos , Sequenciamento Completo do Genoma
5.
Nat Commun ; 12(1): 2491, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941780

RESUMO

Mycobacterium kansasii can cause serious pulmonary disease. It belongs to a group of closely-related species of non-tuberculous mycobacteria known as the M. kansasii complex (MKC). Here, we report a population genomics analysis of 358 MKC isolates from worldwide water and clinical sources. We find that recombination, likely mediated by distributive conjugative transfer, has contributed to speciation and on-going diversification of the MKC. Our analyses support municipal water as a main source of MKC infections. Furthermore, nearly 80% of the MKC infections are due to closely-related M. kansasii strains, forming a main cluster that apparently originated in the 1900s and subsequently expanded globally. Bioinformatic analyses indicate that several genes involved in metabolism (e.g., maintenance of the methylcitrate cycle), ESX-I secretion, metal ion homeostasis and cell surface remodelling may have contributed to M. kansasii's success and its ongoing adaptation to the human host.


Assuntos
Água Potável/microbiologia , Genoma Bacteriano/genética , Pneumopatias/epidemiologia , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Mycobacterium kansasii/genética , Metabolismo Energético/genética , Variação Genética/genética , Genética Populacional/métodos , Genômica , Humanos , Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium kansasii/isolamento & purificação , Virulência/genética , Microbiologia da Água
6.
BMC Genomics ; 22(1): 351, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001009

RESUMO

The past years have seen the rise of genomic biobanks and mega-scale meta-analysis of genomic data, which promises to reveal the genetic underpinnings of health and disease. However, the over-representation of Europeans in genomic studies not only limits the global understanding of disease risk but also inhibits viable research into the genomic differences between carriers and patients. Whilst the community has agreed that more diverse samples are required, it is not enough to blindly increase diversity; the diversity must be quantified, compared and annotated to lead to insight. Genetic annotations from separate biobanks need to be comparable and computable and to operate without access to raw data due to privacy concerns. Comparability is key both for regular research and to allow international comparison in response to pandemics. Here, we evaluate the appropriateness of the most common genomic tools used to depict population structure in a standardized and comparable manner. The end goal is to reduce the effects of confounding and learn from genuine variation in genetic effects on phenotypes across populations, which will improve the value of biobanks (locally and internationally), increase the accuracy of association analyses and inform developmental efforts.


Assuntos
Bancos de Espécimes Biológicos , Pandemias , Genética Populacional , Humanos , Privacidade
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(5): 503-505, 2021 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-33974267

RESUMO

OBJECTIVE: To investigate the genetic polymorphisms of 21 non-combined DNA index system short tandem repeat (STR) loci in Hainan Li population. METHODS: DNA samples from 339 unrelated healthy individuals of Li population from Hainan Province were extracted and amplified with fluorescence labeled multiplex PCR system. PCR products were electrophoresed on an ABI3130 Genetic Analyzer following the manufacturer's instructions. Allele designation was performed with a GeneMapper ID-X by comparison with the allele ladder provided by the corresponding kit. RESULTS: A total of 173 alleles and 489 genotypes were observed for the 21 STR loci, respectively. The frequencies of alleles and genotypes were 0.0010-0.5434 and 0.0020-0.3274, respectively. The heterozygosity varied from 0.639 to 0.833. Discrimination power (DP) was 0.803-0.948, power of exclusion for trio-paternity was 0.416-0.584, power of exclusion for duo-paternity was 0.140-0.238, the polymorphism information content(PIC) was 0.57-0.81, respectively. The total discrimination power (TDP), cumulative probability of exclusion for trio-paternity testing(CPE-trio) and cumulative probability of exclusion for duo-paternity testing (CPE-duo) were 0.999 999 999 999 99, 0.999 999 883 211 752, and 0.987 266, respectively. CONCLUSION: The 21 STR loci are highly polymorphic and informative in the studied population and can be employed as supplementary loci in duo-paternity testing or cases with variant circumstances.


Assuntos
Grupo com Ancestrais do Continente Asiático , Repetições de Microssatélites , Grupo com Ancestrais do Continente Asiático/genética , China , DNA , Frequência do Gene , Genética Populacional , Humanos , Repetições de Microssatélites/genética , Polimorfismo Genético
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(4): 351-360, 2021 Apr 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33967080

RESUMO

OBJECTIVES: Due to the genetic feature of high diversity than other DNA markers, short tandem repeat (STR) plays key roles in forensic, anthropology, and population genetics. Newly introduced multiple STR kit is more valuable because of the greatly improved discriminatory power with the increase in the number of STR loci. The genetic polymorphic data are essential for the application and research in specific population. This study aims to investigate the genetic polymorphism of Han population residing in Yuncheng district, Shanxi Province, to evaluate the application of 23 STR loci in forensic personal identification and paternity test, and to explore the genetic relationship of Han population between Yuncheng and other populations. METHODS: A total of 23 STR loci were amplified from 525 healthy unrelated individuals from the Han nationality in Yuncheng, Shanxi Province using the AGCU EX25 amplification kit. The products were detected and separated by ABI 3500 Genetic Analyzer. Alleles were genotyped by GeneMapper ID (Version 3.2) software, and corresponding frequencies and forensic parameters were calculated. We calculated the genetic distance and plotted the neighboring-joining tree with other 13 population. RESULTS: The allele frequency of the 23 STRs ranged from 0.0010 to 0.5090. No deviation from Hardy-Weinberg equilibrium (P>0.05) and linkage disequilibrium was observed. The cumulative discriminatory power (CPD), cumulative power of exclusion for trios (CPEtrio)and cumulative Power of exclusion for duos (CPEduo) with total 23 STRs were 1-1.305 263 374 8×10-27, 1-2.583 152 052 2×10-10 and 1-1.193 637 500 4×10-6, respectively. Comprehensive population comparison showed that Shanxi Yuncheng Han nationality was genetically closer to populations of the same linguistic family or geographically close proximity, such as Shaanxi Weinan Han, Liaoning Han, and Ningbo Han nationality while relatively far away from different linguistic ethnic groups and geographically distant populations like Xinjiang Uygur and Guangdong Han nationality. CONCLUSIONS: These 23 STRs are highly genetic polymorphic and informative in the Han population of Yuncheng, Shanxi Province, which can provide basic data for forensic personal identification, paternity testing, and population genetic research.


Assuntos
Grupo com Ancestrais do Continente Asiático , Repetições de Microssatélites , Grupo com Ancestrais do Continente Asiático/genética , China , Grupos Étnicos/genética , Frequência do Gene , Loci Gênicos , Genética Populacional , Humanos , Repetições de Microssatélites/genética , Polimorfismo Genético
9.
Nat Commun ; 12(1): 3045, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031378

RESUMO

Conservation breeding programs such as zoos play a major role in preventing extinction, but their sustainability may be impeded by neutral and adaptive population genetic change. These changes are difficult to detect for a single species or context, and impact global conservation efforts. We analyse pedigree data from 15 vertebrate species - over 30,000 individuals - to examine offspring survival over generations of captive breeding. Even accounting for inbreeding, we find that the impacts of increasing generations in captivity are highly variable across species, with some showing substantial increases or decreases in offspring survival over generations. We find further differences between dam and sire effects in first- versus multi-generational analysis. Crucially, our multispecies analysis reveals that responses to captivity could not be predicted from species' evolutionary (phylogenetic) relationships. Even under best-practice captive management, generational fitness changes that cannot be explained by known processes (such as inbreeding depression), are occurring.


Assuntos
Cruzamento , Genética Populacional , Feminino , Humanos , Endogamia , Masculino , Linhagem , Filogenia , Estudos Retrospectivos , Análise de Sobrevida
10.
BMC Infect Dis ; 21(1): 439, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33985447

RESUMO

BACKGROUND: Genetic diversity in Plasmodium falciparum populations can be used to describe the resilience and spatial distribution of the parasite in the midst of intensified intervention efforts. This study used microsatellite analysis to evaluate the genetic diversity and population dynamics of P. falciparum parasites circulating in three ecological zones of Ghana. METHODS: A total of 1168 afebrile children aged between 3 to 13 years were recruited from five (5) Primary schools in 3 different ecological zones (Sahel (Tamale and Kumbungu), Forest (Konongo) and Coastal (Ada and Dodowa)) of Ghana. Asymptomatic malaria parasite carriage was determined using microscopy and PCR, whilst fragment analysis of 6 microsatellite loci was used to determine the diversity and population structure of P. falciparum parasites. RESULTS: Out of the 1168 samples examined, 16.1 and 39.5% tested positive for P. falciparum by microscopy and nested PCR respectively. The genetic diversity of parasites in the 3 ecological zones was generally high, with an average heterozygosity (He) of 0.804, 0.787 and 0.608 the rainy (peak) season for the Sahel, Forest and Coastal zones respectively. The mean He for the dry (off-peak) season were 0.562, 0.693 and 0.610 for the Sahel, Forest and Coastal zones respectively. Parasites from the Forest zone were more closely related to those from the Sahel than from the Coastal zone, despite the Coastal zone being closer in physical distance to the Forest zone. The fixation indexes among study sites ranged from 0.049 to 0.112 during the rainy season and 0.112 to 0.348 during the dry season. CONCLUSION: A large asymptomatic parasite reservoir was found in the school children during both rainy and dry seasons, especially those in the Forest and Sahel savannah zones where parasites were also found to be related compared to those from the Coastal zone. Further studies are recommended to understand why despite the roll out of several malaria interventions in Ghana, high transmission still persist.


Assuntos
Portador Sadio/parasitologia , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Adolescente , Portador Sadio/epidemiologia , Criança , Pré-Escolar , DNA de Protozoário/genética , Feminino , Variação Genética , Genética Populacional , Gana/epidemiologia , Humanos , Malária Falciparum/epidemiologia , Masculino , Repetições de Microssatélites/genética , Plasmodium falciparum/citologia , Plasmodium falciparum/isolamento & purificação , Estações do Ano
11.
Nat Commun ; 12(1): 2080, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33828095

RESUMO

South Eastern Bantu-speaking (SEB) groups constitute more than 80% of the population in South Africa. Despite clear linguistic and geographic diversity, the genetic differences between these groups have not been systematically investigated. Based on genome-wide data of over 5000 individuals, representing eight major SEB groups, we provide strong evidence for fine-scale population structure that broadly aligns with geographic distribution and is also congruent with linguistic phylogeny (separation of Nguni, Sotho-Tswana and Tsonga speakers). Although differential Khoe-San admixture plays a key role, the structure persists after Khoe-San ancestry-masking. The timing of admixture, levels of sex-biased gene flow and population size dynamics also highlight differences in the demographic histories of individual groups. The comparisons with five Iron Age farmer genomes further support genetic continuity over ~400 years in certain regions of the country. Simulated trait genome-wide association studies further show that the observed population structure could have major implications for biomedical genomics research in South Africa.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Demografia , Fluxo Gênico , Estudo de Associação Genômica Ampla , Idioma , Cromossomos Humanos Y/genética , Grupos Étnicos , Feminino , Frequência do Gene , Variação Genética , Genética Populacional , Genômica , Geografia , Haplótipos , Humanos , Linguística , Masculino , Filogenia , África do Sul
12.
Nat Genet ; 53(5): 752-760, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33846635

RESUMO

Lettuce (Lactuca sativa) is an important vegetable crop worldwide. Cultivated lettuce is believed to be domesticated from L. serriola; however, its origins and domestication history remain to be elucidated. Here, we sequenced a total of 445 Lactuca accessions, including major lettuce crop types and wild relative species, and generated a comprehensive map of lettuce genome variations. In-depth analyses of population structure and demography revealed that lettuce was first domesticated near the Caucasus, which was marked by loss of seed shattering. We also identified the genetic architecture of other domestication traits and wild introgressions in major resistance clusters in the lettuce genome. This study provides valuable genomic resources for crop breeding and sheds light on the domestication history of cultivated lettuce.


Assuntos
Domesticação , Ecótipo , Genoma de Planta , Alface/genética , Melhoramento Vegetal , Análise de Sequência de DNA , Loci Gênicos , Variação Genética , Genética Populacional , Humanos , Família Multigênica , Filogenia , Característica Quantitativa Herdável , Seleção Genética
13.
Am J Bot ; 108(4): 680-693, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33881773

RESUMO

PREMISE: The genetic structure between plant populations is facilitated by the spatial population arrangement and limited dispersal of seed and pollen. Saxifraga acerifolia, a local endemic species in Japan, is a habitat specialist that is confined to waterfalls in riparian environments. Its sister species, Saxifraga fortunei, is a generalist that is widely distributed along riverbanks. Here, we examined sympatric populations of the two Saxifraga species to test whether the differences in habitat preference and colonization process influenced regional and local genetic structures. METHODS: To reveal genetic structures, we examined chloroplast microsatellite variations and genome-wide nucleotide polymorphisms obtained by genotyping by sequencing. We also estimated the gene flow among and within populations and performed landscape genetic analyses to evaluate seed and pollen movement and the extent of genetic isolation related to geographic distance and/or habitat differences. RESULTS: We found strong genetic structure in the specialist S. acerifolia, even on a small spatial scale (<1 km part); each population on a different waterfall in one river system had a completely different predominant haplotype. By contrast, the generalist S. fortunei showed no clear genetic differentiation. CONCLUSIONS: Our findings suggest that the level of genetic isolation was increased in S. acerifolia by the spatially fragmented habitat and limited seed and pollen dispersal over waterfalls. Habitat differentiation between the sister taxa could have contributed to the different patterns of gene flow and then shaped the contrasting genetic structures.


Assuntos
Variação Genética , Saxifragaceae , Ecossistema , Fluxo Gênico , Genética Populacional , Japão , Repetições de Microssatélites/genética , Saxifragaceae/genética , Simpatria
14.
BMC Genomics ; 22(1): 273, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858341

RESUMO

BACKGROUND: Messenger RNA sequencing is becoming more common in studies of non-model species and is most often used for gene expression-based investigations. However, the method holds potential for numerous other applications as well-including analyses of alternative splicing, population structure, and signatures of selection. To maximize the utility of mRNA data sets, distinct analyses may be combined such as by exploring dynamics between gene expression with signatures of selection in the context of population structure. Here, we compare two published data sets describing two populations of a minnow species endemic to the San Francisco Estuary (Sacramento splittail, Pogonichthys macrolepidotus): a microsatellite data set showing population structure, and an mRNA whole transcriptome data set obtained after the two populations were exposed to a salinity challenge. We compared measures of population structure and genetic variation using single nucleotide polymorphisms (SNPs) called from mRNA from the whole transcriptome sequencing study with those patterns determined from microsatellites. For investigating plasticity and evolution, intra- and inter-population transcriptome plasticity was investigated with differential gene expression, differential exon usage, and gene expression variation. Outlier SNP analysis was also performed on the mRNA data set and signatures of selection and phenotypic plasticity were investigated on an individual-gene basis. RESULTS: We found that mRNA sequencing revealed patterns of population structure consistent with those found with microsatellites, but with lower magnitudes of genetic variation and population differentiation consistent with widespread purifying selection expected when using mRNA. In addition, within individual genes, phenotypic plasticity or signatures of selection were found in almost mutual exclusion (except heatr6, nfu1, slc22a6, sya, and mmp13). CONCLUSIONS: These results show that an mRNA sequencing data set may have multiple uses, including describing population structure and for investigating the mechanistic interplay of evolution and plasticity in adaptation. MRNA sequencing thus complements traditional sequencing methods used for population genetics, in addition to its utility for describing phenotypic plasticity.


Assuntos
Cyprinidae , Genética Populacional , Animais , Repetições de Microssatélites/genética , Polimorfismo de Nucleotídeo Único , Seleção Genética , Análise de Sequência de RNA , Sequenciamento Completo do Exoma
16.
Am J Hum Genet ; 108(4): 656-668, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33770507

RESUMO

Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.


Assuntos
Análise Mutacional de DNA/economia , Análise Mutacional de DNA/normas , Variação Genética/genética , Genética Populacional/economia , África , Análise Mutacional de DNA/métodos , Genética Populacional/métodos , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Equidade em Saúde , Humanos , Microbiota , Sequenciamento Completo do Genoma/economia , Sequenciamento Completo do Genoma/normas
17.
BMC Bioinformatics ; 22(1): 114, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750289

RESUMO

BACKGROUND: Y-chromosome DNA (Y-DNA) has been used for tracing paternal lineages and offers a clear path from an individual to a known, or likely, direct paternal ancestor. The advance of next-generation sequencing (NGS) technologies increasingly improves the resolution of the non-recombining region of the Y-chromosome (NRY). However, a lack of suitable computer tools prevents the use of NGS data from the Y-DNA studies. RESULTS: We developed Y-LineageTracker, a high-throughput analysis framework that not only utilizes state-of-the-art methodologies to automatically determine NRY haplogroups and identify microsatellite variants of Y-chromosome on a fine scale, but also optimizes comprehensive Y-DNA analysis methods for NGS data. Notably, Y-LineageTracker integrates the NRY haplogroup and Y-STR analysis modules with recognized strategies to robustly suggest an interpretation for paternal genetics and evolution. NRY haplogroup module mainly covers haplogroup classification, clustering analysis, phylogeny construction, and divergence time estimation of NRY haplogroups, and Y-STR module mainly includes Y-STR genotyping, statistical calculation, network analysis, and estimation of time to the most recent common ancestor (TMRCA) based on Y-STR haplotypes. Performance comparison indicated that Y-LineageTracker outperformed existing Y-DNA analysis tools for the high performance and satisfactory visualization effect. CONCLUSIONS: Y-LineageTracker is an open-source and user-friendly command-line tool that provide multiple functions to efficiently analyze Y-DNA from NGS data at both Y-SNP and Y-STR level. Additionally, Y-LineageTracker supports various formats of input data and produces high-quality figures suitable for publication. Y-LineageTracker is coded with Python3 and supports Windows, Linux, and macOS platforms, and can be installed manually or via the Python Package Index (PyPI). The source code, examples, and manual of Y-LineageTracker are freely available at https://www.picb.ac.cn/PGG/resource.php or CodeOcean ( https://codeocean.com/capsule/7424381/tree ).


Assuntos
Cromossomos Humanos Y , Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , Cromossomos Humanos Y/genética , Genética Populacional , Haplótipos , Humanos , Repetições de Microssatélites
18.
Am J Hum Genet ; 108(4): 620-631, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33691092

RESUMO

Phenotype prediction is a key goal for medical genetics. Unfortunately, most genome-wide association studies are done in European populations, which reduces the accuracy of predictions via polygenic scores in non-European populations. Here, we use population genetic models to show that human demographic history and negative selection on complex traits can result in population-specific genetic architectures. For traits where alleles with the largest effect on the trait are under the strongest negative selection, approximately half of the heritability can be accounted for by variants in Europe that are absent from Africa, leading to poor performance in phenotype prediction across these populations. Further, under such a model, individuals in the tails of the genetic risk distribution may not be identified via polygenic scores generated in another population. We empirically test these predictions by building a model to stratify heritability between European-specific and shared variants and applied it to 37 traits and diseases in the UK Biobank. Across these phenotypes, ∼30% of the heritability comes from European-specific variants. We conclude that genetic association studies need to include more diverse populations to enable the utility of phenotype prediction in all populations.


Assuntos
Predisposição Genética para Doença , Genética Populacional , Modelos Genéticos , Herança Multifatorial/genética , Fenótipo , Seleção Genética/genética , África/etnologia , Simulação por Computador , Conjuntos de Dados como Assunto , Europa (Continente)/etnologia , Variação Genética/genética , Humanos , Crescimento Demográfico , Reino Unido
19.
Am J Hum Genet ; 108(3): 395-399, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33667393

RESUMO

This article is based on the address given by the author at the 2020 virtual meeting of the American Society of Human Genetics (ASHG) on October 26, 2020. The video of the original address can be found at the ASHG website.


Assuntos
Consanguinidade , Genética Médica/tendências , Genética Populacional/tendências , Genoma Humano/genética , Humanos , Anotação de Sequência Molecular
20.
Mol Genet Genomics ; 296(3): 631-651, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33650010

RESUMO

Trans-Eurasian cultural and genetic exchanges have significantly influenced the demographic dynamics of Eurasian populations. The Hexi Corridor, located along the southeastern edge of the Eurasian steppe, served as an important passage of the ancient Silk Road in Northwest China and intensified the transcontinental exchange and interaction between populations on the Central Plain and in Western Eurasia. Historical and archeological records indicate that the Western Eurasian cultural elements were largely brought into North China via this geographical corridor, but there is debate on the extent to which the spread of barley/wheat agriculture into North China and subsequent Bronze Age cultural and technological mixture/shifts were achieved by the movement of people or dissemination of ideas. Here, we presented higher-resolution genome-wide autosomal and uniparental Y/mtDNA SNP or STR data for 599 northwestern Han Chinese individuals and conducted 2 different comprehensive genetic studies among Neolithic-to-present-day Eurasians. Genetic studies based on lower-resolution STR markers via PCA, STRUCTURE, and phylogenetic trees showed that northwestern Han Chinese individuals had increased genetic homogeneity relative to northern Mongolic/Turkic/Tungusic speakers and Tibeto-Burman groups. The genomic signature constructed based on modern/ancient DNA further illustrated that the primary ancestry of the northwestern Han was derived from northern millet farmer ancestors, which was consistent with the hypothesis of Han origin in North China and more recent northwestward population expansion. This was subsequently confirmed via excess shared derived alleles in f3/f4 statistical analyses and by more northern East Asian-related ancestry in the qpAdm/qpGraph models. Interestingly, we identified one western Eurasian admixture signature that was present in northwestern Han but absent from southern Han, with an admixture time dated to approximately 1000 CE (Tang and Song dynasties). Generally, we provided supporting evidence that historic Trans-Eurasian communication was primarily maintained through population movement, not simply cultural diffusion. The observed population dynamics in northwestern Han Chinese not only support the North China origin hypothesis but also reflect the multiple sources of the genetic diversity observed in this population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Genoma/genética , China , Cromossomos Humanos Y/genética , DNA Antigo , DNA Mitocondrial/genética , Grupos Étnicos/genética , Genética Populacional/métodos , Estudo de Associação Genômica Ampla/métodos , Migração Humana , Humanos , Filogenia , Polimorfismo de Nucleotídeo Único/genética
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