Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31.278
Filtrar
1.
Nat Commun ; 13(1): 4482, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918324

RESUMO

Whole-genome recoding has been shown to enable nonstandard amino acids, biocontainment and viral resistance in bacteria. Here we take the first steps to extend this to human cells demonstrating exceptional base editing to convert TAG to TAA for 33 essential genes via a single transfection, and examine base-editing genome-wide (observing ~40 C-to-T off-target events in essential gene exons). We also introduce GRIT, a computational tool for recoding. This demonstrates the feasibility of recoding, and highly multiplex editing in mammalian cells.


Assuntos
Edição de Genes , Genoma Humano , Animais , Sistemas CRISPR-Cas/genética , Códon de Terminação , Éxons , Genes Essenciais , Genoma Humano/genética , Humanos , Mamíferos/genética
2.
Nat Commun ; 13(1): 4384, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927245

RESUMO

Graph-based genome reference representations have seen significant development, motivated by the inadequacy of the current human genome reference to represent the diverse genetic information from different human populations and its inability to maintain the same level of accuracy for non-European ancestries. While there have been many efforts to develop computationally efficient graph-based toolkits for NGS read alignment and variant calling, methods to curate genomic variants and subsequently construct genome graphs remain an understudied problem that inevitably determines the effectiveness of the overall bioinformatics pipeline. In this study, we discuss obstacles encountered during graph construction and propose methods for sample selection based on population diversity, graph augmentation with structural variants and resolution of graph reference ambiguity caused by information overload. Moreover, we present the case for iteratively augmenting tailored genome graphs for targeted populations and demonstrate this approach on the whole-genome samples of African ancestry. Our results show that population-specific graphs, as more representative alternatives to linear or generic graph references, can achieve significantly lower read mapping errors and enhanced variant calling sensitivity, in addition to providing the improvements of joint variant calling without the need of computationally intensive post-processing steps.


Assuntos
Análise de Dados , Sequenciamento de Nucleotídeos em Larga Escala , Genoma Humano/genética , Genômica/métodos , Humanos , Análise de Sequência de DNA/métodos , Software
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(8): 814-818, 2022 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-35929928

RESUMO

OBJECTIVE: Through a retrospective large sample analysis of copy number variants in single center, we explored the technical standards for the interpretation and reporting of constitutional copy-number variants (CNVs) jointly proposed by the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) in 2019, analyzing its impact on CNVs ratings and the improvement in the consistency of the classification of CNVs in clinical laboratories. METHODS: 236 CNVs that assessed as pathogenic, uncertain significant (including likely pathogenic, uncertain and likely benign) by the 2011 ACMG guidelines between August 2018 and December 2019 in our center were re-analyzed. Four working group members of the center reclassified and evaluated 235 CNVs according to 2019 ACMG guidelines. RESULTS: The consistency of clinical significance classification of CNVs was 91% and the α test coefficient was 0.98 among four working group members. Compared with the 2011 and 2019 ACMG technical standards for the CNVs classification, evaluation of pathogenicity and uncertain significant is basically consistent. 90% (45/50) of likely pathogenic and likely benign CNVs were Re-evaluated as variants of uncertain significance, and the difference is significant. CONCLUSION: The new version ACMG/ClinGen guidelines for the evaluation of CNVs developed semi-quantitative point-based scoring system and help to improve the consistency in clinical classifications. It can also make the interpretation of CNVs more standardized and transparent.


Assuntos
Variações do Número de Cópias de DNA , Genoma Humano , Testes Genéticos , Variação Genética , Humanos , Mutação , Estudos Retrospectivos
4.
PLoS Comput Biol ; 18(8): e1010393, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35947558

RESUMO

Somatic mutations in cancer genomes are associated with DNA replication timing (RT) and chromatin accessibility (CA), however these observations are based on normal tissues and cell lines while primary cancer epigenomes remain uncharacterised. Here we use machine learning to model megabase-scale mutation burden in 2,500 whole cancer genomes and 17 cancer types via a compendium of 900 CA and RT profiles covering primary cancers, normal tissues, and cell lines. CA profiles of primary cancers, rather than those of normal tissues, are most predictive of regional mutagenesis in most cancer types. Feature prioritisation shows that the epigenomes of matching cancer types and organ systems are often the strongest predictors of regional mutation burden, highlighting disease-specific associations of mutational processes. The genomic distributions of mutational signatures are also shaped by the epigenomes of matched cancer and tissue types, with SBS5/40, carcinogenic and unknown signatures most accurately predicted by our models. In contrast, fewer associations of RT and regional mutagenesis are found. Lastly, the models highlight genomic regions with overrepresented mutations that dramatically exceed epigenome-derived expectations and show a pan-cancer convergence to genes and pathways involved in development and oncogenesis, indicating the potential of this approach for coding and non-coding driver discovery. The association of regional mutational processes with the epigenomes of primary cancers suggests that the landscape of passenger mutations is predominantly shaped by the epigenomes of cancer cells after oncogenic transformation.


Assuntos
Cromatina , Neoplasias , Carcinogênese/genética , Cromatina/genética , Genoma Humano/genética , Humanos , Mutagênese , Mutação/genética , Neoplasias/genética , Neoplasias/patologia , Oncogenes
5.
Transl Psychiatry ; 12(1): 317, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933470

RESUMO

The association between extent of chronic cannabis use (CCU-extent) and cognitive impairment among adolescents has been the subject of controversial debate. Linking DNA methylation to CCU-extent could help to understand cannabis associated changes in cognitive performance. We analyzed cognitive task performances, CpG methylation in peripheral whole-blood samples and self-reported past-year CCU-extent of n = 18 adolescents (n = 9 psychiatric outpatients with chronic cannabis use (CCU), n = 9 without) who were matched for age, gender and psychiatric disorders. Patients with CCU were at least 24 h abstinent when cognitive tasks were performed. A Principal Component Analysis (PCA) was carried out to identify group differences in whole genome DNA methylation. Mediation analyses were performed between CCU-extent associated CpG sites and CCU-extent associated variables of cognitive tasks. PCA results indicated large differences in whole genome DNA methylation levels between the groups that did not reach statistical significance. Six CpG sites revealed reduced methylation associated with CCU-extent. Furthermore, CCU-extent was associated with lower scores in verbal learning. All six CpG sites mediated the effects between CCU-extent and verbal learning free recall. Our results indicate that CCU is associated with certain patterns in the methylome. Furthermore, CCU-extent associated impairments in memory function are mediated via differential methylation of the six CCU-associated CpG sits. Six identified CpG are located in genes previously described in the context of neurodegeneration, hippocampus-dependent learning and neurogenesis. However, these results have to be carefully interpreted due to a small sample size. Replication studies are warranted.


Assuntos
Cannabis , Alucinógenos , Adolescente , Ilhas de CpG , DNA , Metilação de DNA , Genoma Humano , Humanos , Aprendizagem Verbal
6.
Cell ; 185(16): 3041-3055.e25, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35917817

RESUMO

Rare copy-number variants (rCNVs) include deletions and duplications that occur infrequently in the global human population and can confer substantial risk for disease. In this study, we aimed to quantify the properties of haploinsufficiency (i.e., deletion intolerance) and triplosensitivity (i.e., duplication intolerance) throughout the human genome. We harmonized and meta-analyzed rCNVs from nearly one million individuals to construct a genome-wide catalog of dosage sensitivity across 54 disorders, which defined 163 dosage sensitive segments associated with at least one disorder. These segments were typically gene dense and often harbored dominant dosage sensitive driver genes, which we were able to prioritize using statistical fine-mapping. Finally, we designed an ensemble machine-learning model to predict probabilities of dosage sensitivity (pHaplo & pTriplo) for all autosomal genes, which identified 2,987 haploinsufficient and 1,559 triplosensitive genes, including 648 that were uniquely triplosensitive. This dosage sensitivity resource will provide broad utility for human disease research and clinical genetics.


Assuntos
Variações do Número de Cópias de DNA , Genoma Humano , Variações do Número de Cópias de DNA/genética , Dosagem de Genes , Haploinsuficiência/genética , Humanos
7.
PLoS One ; 17(8): e0271097, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35960716

RESUMO

The ancestry of each locus of the genome can be estimated (local ancestry) based on sequencing or genotyping information together with reference panels of ancestral source populations. The length of those ancestry-specific genomic segments are commonly used to understand migration waves and admixture events. In short time scales, it is often of interest to determine the existence of the most recent unadmixed ancestor from a specific population t generations ago. We built a hypothesis test to determine if an individual has an ancestor belonging to a target ancestral population t generations ago based on these lengths of the ancestry-specific segments at an individual level. We applied this test on a data set that includes 20 Uruguayan admixed individuals to estimate for each one how many generations ago the most recent indigenous ancestor lived. As this method tests each individual separately, it is particularly suited to small sample sizes, such as our study or ancient genome samples.


Assuntos
Genética Populacional , Polimorfismo de Nucleotídeo Único , Genoma Humano , Humanos , Uruguai
8.
Mol Biol Evol ; 39(8)2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35920169

RESUMO

The Massim, a cultural region that includes the southeastern tip of mainland Papua New Guinea (PNG) and nearby PNG offshore islands, is renowned for a trading network called Kula, in which different valuable items circulate in different directions among some of the islands. Although the Massim has been a focus of anthropological investigation since the pioneering work of Malinowski in 1922, the genetic background of its inhabitants remains relatively unexplored. To characterize the Massim genomically, we generated genome-wide SNP data from 192 individuals from 15 groups spanning the entire region. Analyzing these together with comparative data, we found that all Massim individuals have variable Papuan-related (indigenous) and Austronesian-related (arriving ∼3,000 years ago) ancestries. Individuals from Rossel Island in southern Massim, speaking an isolate Papuan language, have the highest amount of a distinct Papuan ancestry. We also investigated the recent contact via sharing of identical by descent (IBD) genomic segments and found that Austronesian-related IBD tracts are widely distributed geographically, but Papuan-related tracts are shared exclusively between the PNG mainland and Massim, and between the Bismarck and Solomon Archipelagoes. Moreover, the Kula-practicing groups of the Massim show higher IBD sharing among themselves than do groups that do not participate in Kula. This higher sharing predates the formation of Kula, suggesting that extensive contact between these groups since the Austronesian settlement may have facilitated the formation of Kula. Our study provides the first comprehensive genome-wide assessment of Massim inhabitants and new insights into the fascinating Kula system.


Assuntos
Genoma Humano , Humanos , Papua Nova Guiné
9.
BMC Genomics ; 23(1): 487, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787153

RESUMO

Investigating the functions and activities of genes requires proper annotation of the transcribed units. However, transcript assembly efforts have produced a surprisingly large variation in the number of transcripts, and especially so for noncoding transcripts. This heterogeneity in assembled transcript sets might be partially explained by sequencing depth. Here, we used real and simulated short-read sequencing data as well as long-read data to systematically investigate the impact of sequencing depths on the accuracy of assembled transcripts. We assembled and analyzed transcripts from 671 human short-read data sets and four long-read data sets. At the first level, there is a positive correlation between the number of reads and the number of recovered transcripts. However, the effect of the sequencing depth varied based on cell or tissue type, the type of read and the nature and expression levels of the transcripts. The detection of coding transcripts saturated rapidly with both short and long-reads, however, there was no sign of early saturation for noncoding transcripts at any sequencing depth. Increasing long-read sequencing depth specifically benefited transcripts containing transposable elements. Finally, we show how single-cell RNA-seq can be guided by transcripts assembled from bulk long-read samples, and demonstrate that noncoding transcripts are expressed at similar levels to coding transcripts but are expressed in fewer cells. This study highlights the impact of sequencing depth on transcript assembly.


Assuntos
Elementos de DNA Transponíveis , Genoma Humano , Teste de Histocompatibilidade , Humanos , Sequenciamento Completo do Exoma
10.
Sci Rep ; 12(1): 11928, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831384

RESUMO

Scarless genome editing of induced pluripotent stem cells (iPSCs) is crucial for the precise modeling of genetic disease. Here we present CRISPR Del/Rei, a two-step deletion-reinsertion strategy with high editing efficiency and simple PCR-based screening that generates isogenic clones in ~ 2 months. We apply our strategy to edit iPSCs at 3 loci with only rare off target editing.


Assuntos
Edição de Genes , Células-Tronco Pluripotentes Induzidas , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Genoma Humano , Humanos
11.
Genes (Basel) ; 13(7)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35885907

RESUMO

Diagnostic genetics within the United Kingdom National Health Service (NHS) has undergone many stepwise improvements in technology since the completion of the human genome project in 2003. Although Sanger sequencing has remained a cornerstone of the diagnostic sequencing arena, the human genome reference sequence has enabled next-generation sequencing (more accurately named 'second-generation sequencing'), to rapidly surpass it in scale and potential. This mini review discusses such developments from the viewpoint of the Stickler's higher specialist service, detailing the considerations and improvements to diagnostic sequencing implemented since 2003.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Medicina Estatal , Genoma Humano , Humanos , Síndrome , Tecnologia
12.
Sci Rep ; 12(1): 12457, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864128

RESUMO

The 2018 Hearing Loss Expert Panel (HL-EP)-specific guidelines specified from the universal 2015 ACMG/AMP guidelines are proposed to be used in genetic HL, which prompted this study. A genetic HL cohort comprising 135 unrelated probands with available exome sequencing data was established. Overall, 169 variants were prioritized as candidates and interpreted using the 2015 ACMG/AMP and 2018 HL-EP guidelines. Changes in rule application and variant classification between the guidelines were compared. The concordance rate of variant classification of each variant between the guidelines was 71.60%, with significant difference. The proportion of pathogenic variants increased from 13.02% (2015) to 29.59% (2018). Variant classifications of autosomal recessive (AR) variants that previously belonged to VUS or likely pathogenic in the 2015 guidelines were changed toward pathogenic in the 2018 guidelines more frequently than those of autosomal dominant variants (29.17% vs. 6.38%, P = 0.005). Stratification of the PM3 and PP1 rules in the 2018 guidelines led to more substantial escalation than that in the 2015 guidelines. We compared the disease-specific guidelines (2018) with the universal guidelines (2015) using real-world data. Owing to the sophistication of case-level data, the HL-specific guidelines have more explicitly classified AR variants toward "likely pathogenic" or "pathogenic", serving as potential references for other recessive genetic diseases.


Assuntos
Surdez , Perda Auditiva , Monofosfato de Adenosina , Surdez/genética , Testes Genéticos , Variação Genética , Genoma Humano , Perda Auditiva/diagnóstico , Perda Auditiva/genética , Humanos
13.
Curr Biol ; 32(14): 3095-3109.e5, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35839766

RESUMO

Southern East Asia is the dispersal center regarding the prehistoric settlement and migrations of modern humans in Asia-Pacific regions. However, the settlement pattern and population structure of paleolithic humans in this region remain elusive, and ancient DNA can provide direct information. Here, we sequenced the genome of a Late Pleistocene hominin (MZR), dated ∼14.0 thousand years ago from Red Deer Cave located in Southwest China, which was previously reported possessing mosaic features of modern and archaic hominins. MZR is the first Late Pleistocene genome from southern East Asia. Our results indicate that MZR is a modern human who represents an early diversified lineage in East Asia. The mtDNA of MZR belongs to an extinct basal lineage of the M9 haplogroup, reflecting a rich matrilineal diversity in southern East Asia during the Late Pleistocene. Combined with the published data, we detected clear genetic stratification in ancient southern populations of East/Southeast Asia and some degree of south-versus-north divergency during the Late Pleistocene, and MZR was identified as a southern East Asian who exhibits genetic continuity to present day populations. Markedly, MZR is linked deeply to the East Asian ancestry that contributed to First Americans.


Assuntos
Cervos , Hominidae , Animais , China , Fósseis , Genoma Humano , Humanos
14.
Hum Mutat ; 43(8): 973-975, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35839310

RESUMO

The journal Human Mutation has as its principal focus variants in the human genome, covering the entire spectrum from methods used to detect variants, to ways of answering the ultimate question: "What are the consequences of carrying a variant for the health of the individual?" This comprehensive collection of articles provides an excellent perspective of the advancements in variant effect prediction in recent years, as well as some caveats and cautions in this developing field. We believe that this resource will help to drive further evolution of the variant effect prediction process toward more robust understanding of genotype-phenotype relationships through reliable variant classification.


Assuntos
Genoma Humano , Genoma Humano/genética , Humanos , Mutação , Fenótipo
15.
Nature ; 607(7920): 799-807, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35859169

RESUMO

The APOBEC3 family of cytosine deaminases has been implicated in some of the most prevalent mutational signatures in cancer1-3. However, a causal link between endogenous APOBEC3 enzymes and mutational signatures in human cancer genomes has not been established, leaving the mechanisms of APOBEC3 mutagenesis poorly understood. Here, to investigate the mechanisms of APOBEC3 mutagenesis, we deleted implicated genes from human cancer cell lines that naturally generate APOBEC3-associated mutational signatures over time4. Analysis of non-clustered and clustered signatures across whole-genome sequences from 251 breast, bladder and lymphoma cancer cell line clones revealed that APOBEC3A deletion diminished APOBEC3-associated mutational signatures. Deletion of both APOBEC3A and APOBEC3B further decreased APOBEC3 mutation burdens, without eliminating them. Deletion of APOBEC3B increased APOBEC3A protein levels, activity and APOBEC3A-mediated mutagenesis in some cell lines. The uracil glycosylase UNG was required for APOBEC3-mediated transversions, whereas the loss of the translesion polymerase REV1 decreased overall mutation burdens. Together, these data represent direct evidence that endogenous APOBEC3 deaminases generate prevalent mutational signatures in human cancer cells. Our results identify APOBEC3A as the main driver of these mutations, indicate that APOBEC3B can restrain APOBEC3A-dependent mutagenesis while contributing its own smaller mutation burdens and dissect mechanisms that translate APOBEC3 activities into distinct mutational signatures.


Assuntos
Desaminases APOBEC , Mutagênese , Neoplasias , Desaminases APOBEC/deficiência , Desaminases APOBEC/genética , Desaminases APOBEC/metabolismo , Linhagem Celular Tumoral , DNA Polimerase Dirigida por DNA/metabolismo , Deleção de Genes , Genoma Humano , Humanos , Mutagênese/genética , Neoplasias/enzimologia , Neoplasias/genética , Neoplasias/patologia , Uracila-DNA Glicosidase/metabolismo
16.
Nature ; 607(7920): 732-740, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35859178

RESUMO

Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data1,2. Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank3. This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. This large set of variants allows us to characterize selection based on sequence variation within a population through a depletion rank score of windows along the genome. Depletion rank analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UK Biobank: a large British Irish cohort, a smaller African cohort and a South Asian cohort. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation.


Assuntos
Bancos de Espécimes Biológicos , Bases de Dados Genéticas , Variação Genética , Genoma Humano , Genômica , Sequenciamento Completo do Genoma , África/etnologia , Ásia/etnologia , Estudos de Coortes , Sequência Conservada , Éxons/genética , Genoma Humano/genética , Haplótipos/genética , Humanos , Mutação INDEL , Irlanda/etnologia , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único/genética , Reino Unido
17.
Viruses ; 14(7)2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35891351

RESUMO

Human endogenous retroviruses (HERVs) are viral "fossils" in the human genome that originated from the ancient integration of exogenous retroviruses. Although HERVs have sporadically been reported in nonhuman primate genomes, their deep origination in pan-primates remains to be explored. Hence, based on the in silico genomic mining of full-length HERVs in 49 primates, we performed the largest systematic survey to date of the distribution, phylogeny, and functional predictions of HERVs. Most importantly, we obtained conclusive evidence of nonhuman origin for most contemporary HERVs. We found that various supergroups, including HERVW9, HUERSP, HSERVIII, HERVIPADP, HERVK, and HERVHF, were widely distributed in Strepsirrhini, Platyrrhini (New World monkeys) and Catarrhini (Old World monkeys and apes). We found that numerous HERVHFs are spread by vertical transmission within Catarrhini and one HERVHF was traced in 17 species, indicating its ancient nature. We also discovered that 164 HERVs were likely involved in genomic rearrangement and 107 HERVs were potentially coopted in the form of noncoding RNAs (ncRNAs) in humans. In summary, we provided comprehensive data on the deep origination of modern HERVs in pan-primates.


Assuntos
Retrovirus Endógenos , Animais , Cercopithecidae , Retrovirus Endógenos/genética , Evolução Molecular , Genoma Humano , Humanos , Filogenia , Platirrinos
19.
BMC Genomics ; 23(1): 497, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804296

RESUMO

BACKGROUND: Emerging infectious disease-causing RNA viruses, such as the SARS-CoV-2 and Ebola viruses, are thought to rely on bats as natural reservoir hosts. Since these zoonotic viruses pose a great threat to humans, it is important to characterize the bat genome from multiple perspectives. Unsupervised machine learning methods for extracting novel information from big sequence data without prior knowledge or particular models are highly desirable for obtaining unexpected insights. We previously established a batch-learning self-organizing map (BLSOM) of the oligonucleotide composition that reveals novel genome characteristics from big sequence data. RESULTS: In this study, using the oligonucleotide BLSOM, we conducted a comparative genomic study of humans and six bat species. BLSOM is an explainable-type machine learning algorithm that reveals the diagnostic oligonucleotides contributing to sequence clustering (self-organization). When unsupervised machine learning reveals unexpected and/or characteristic features, these features can be studied in more detail via the much simpler and more direct standard distribution map method. Based on this combined strategy, we identified the Mb-level enrichment of CG dinucleotide (Mb-level CpG islands) around the termini of bat long-scaffold sequences. In addition, a class of CG-containing oligonucleotides were enriched in the centromeric and pericentromeric regions of human chromosomes. Oligonucleotides longer than tetranucleotides often represent binding motifs for a wide variety of proteins (e.g., transcription factor binding sequences (TFBSs)). By analyzing the penta- and hexanucleotide composition, we observed the evident enrichment of a wide range of hexanucleotide TFBSs in centromeric and pericentromeric heterochromatin regions on all human chromosomes. CONCLUSION: Function of transcription factors (TFs) beyond their known regulation of gene expression (e.g., TF-mediated looping interactions between two different genomic regions) has received wide attention. The Mb-level TFBS and CpG islands are thought to be involved in the large-scale nuclear organization, such as centromere and telomere clustering. TFBSs, which are enriched in centromeric and pericentromeric heterochromatin regions, are thought to play an important role in the formation of nuclear 3D structures. Our machine learning-based analysis will help us to understand the differential features of nuclear 3D structures in the human and bat genomes.


Assuntos
COVID-19 , Quirópteros/genética , Genoma Humano/genética , SARS-CoV-2/fisiologia , Animais , COVID-19/transmissão , Quirópteros/virologia , Ilhas de CpG , Genômica/métodos , Heterocromatina/química , Heterocromatina/genética , Humanos , Conformação Molecular , Oligonucleotídeos/química , Aprendizado de Máquina não Supervisionado
20.
Int J Mol Sci ; 23(13)2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35806097

RESUMO

Modern PCR-based analytical techniques have reached sensitivity levels that allow for obtaining complete forensic DNA profiles from even tiny traces containing genomic DNA amounts as small as 125 pg. Yet these techniques have reached their limits when it comes to the analysis of traces such as fingerprints or single cells. One suggestion to overcome these limits has been the usage of whole genome amplification (WGA) methods. These methods aim at increasing the copy number of genomic DNA and by this means generate more template DNA for subsequent analyses. Their application in forensic contexts has so far remained mostly an academic exercise, and results have not shown significant improvements and even have raised additional analytical problems. Until very recently, based on these disappointments, the forensic application of WGA seems to have largely been abandoned. In the meantime, however, novel improved methods are pointing towards a perspective for WGA in specific forensic applications. This review article tries to summarize current knowledge about WGA in forensics and suggests the forensic analysis of single-donor bioparticles and of single cells as promising applications.


Assuntos
Impressões Digitais de DNA , Genoma Humano , DNA/análise , DNA/genética , Impressões Digitais de DNA/métodos , Humanos , Repetições de Microssatélites , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...