Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 76
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nat Neurosci ; 22(10): 1617-1623, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31551603

RESUMO

Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.

2.
J Cogn Neurosci ; : 1-20, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31560270

RESUMO

When engaged in dynamic visuospatial tasks, the brain copes with perceptual and cognitive processing challenges. During multiple-object tracking (MOT), the number of objects to be tracked (i.e., load) imposes attentional demands, but so does spatial interference from irrelevant objects (i.e., close encounters). Presently, it is not clear whether the effect of load on accuracy solely depends on the number of close encounters. If so, the same cognitive and physiological mechanisms deal with increasing load by preparing for and dealing with spatial interference. However, this has never been directly tested. Such knowledge is important to understand the neurophysiology of dynamic visual attention and resolve conflicting views within visual cognition concerning sources of capacity limitations. We varied the processing challenge in MOT task in two ways: the number of targets and the minimum spatial proximity between targets and distractors. In a first experiment, we measured task-induced pupil dilations and saccades during MOT. In a separate cohort, we measured fMRI activity. In both cohorts, increased load and close encounters (i.e., close spatial proximity) led to reduced accuracy in an additive manner. Load was associated with pupil dilations, whereas close encounters were not. Activity in dorsal attentional areas and frequency of saccades were proportionally larger both with higher levels of load and close encounters. Close encounters recruited additionally ventral attentional areas that may reflect orienting mechanisms. The activity in two brainstem nuclei, ventral tegmental area/substantia nigra and locus coeruleus, showed clearly dissociated patterns. Our results constitute convergent evidence indicating that different mechanisms underlie processing challenges due to load and object spacing.

3.
Am J Hum Genet ; 105(2): 334-350, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374203

RESUMO

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected ("concordant") direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive ("discordant") relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10-8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms-early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways-that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness.

4.
Schizophr Bull ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31206164

RESUMO

BACKGROUND: Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. METHODS: We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases. RESULTS: PRS for both population IQ (P = 4.39 × 10-28) and EA (P = 1.27 × 10-26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS. CONCLUSIONS: Cognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.

6.
Int J Psychophysiol ; 140: 1-7, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30894328

RESUMO

Dynamic non-luminance-mediated changes in pupil diameter have frequently been shown to be a reliable index for the level of arousal, mental effort, and activity in the locus coeruleus, the brainstem's noradrenergic arousal center. While pupillometry has most commonly been used to assess the level of arousal in particular psychological states or the level of engagement in cognitive tasks, some recent studies have found a relationship between average resting-state (i.e. baseline) pupil sizes and individuals' working memory capacity (WMC), indicating that individuals with higher WMC on average have larger pupils than individuals with relatively lower WMC. In the present study, we measured pupil size continuously in 212 participants during rest (i.e. while fixating) and estimated WMC in all participants by administering the Letter-Number Sequencing (LNS) task from WAIS-III. We were unable to replicate the relation between average pupil size and WMC. However, the novel finding was that higher WMC was associated with higher variability in resting-state pupil size. The present results are relevant for the current debate on the role of noradrenergic activity on working memory capacity.

7.
Cogn Affect Behav Neurosci ; 19(4): 1094, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30815846

RESUMO

The article Task context load induces reactive cognitive control.

8.
Mol Psychiatry ; 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30705424

RESUMO

Prior to and following the publication of this article the authors noted that the complete list of authors was not included in the main article and was only present in Supplementary Table 1. The author list in the original article has now been updated to include all authors, and Supplementary Table 1 has been removed. All other supplementary files have now been updated accordingly. Furthermore, in Table 1 of this Article, the replication cohort for the row Close relative in data set, n (%) was incorrect. All values have now been corrected to 0(0%). The publishers would like to apologise for this error and the inconvenience it may have caused.

9.
Cogn Affect Behav Neurosci ; 19(4): 945-965, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30659515

RESUMO

Cognitive control is a highly dynamic process that relies on flexible engagement of prefrontal areas and of neuromodulatory systems in order to adapt to changing demands. A range of internal and external factors come into play when individuals engage in a task requiring cognitive control. Here we investigated whether increased working memory (WM) demands would induce a flexible change in cognitive control mode in young healthy individuals. We developed a novel variant of the well-known AX-continuous performance task (AX-CPT). We manipulated the cognitive demands of maintaining task-relevant contextual information and studied the impact of this manipulation on behavior and brain activity. We expected that low WM load would allow for a more effortful, proactive strategy, while high WM load would induce a strategy of less effortful, stimulus-driven reactive control. In line with our hypothesis, a web-based experiment revealed that increased load was associated with more reactive behavioral responses, and this finding was independently replicated in behavioral data acquired in the MRI scanner. The results from brain activity showed that the right dorsolateral prefrontal cortex was activated by cues in the proactive mode and by probes in the reactive mode. The analysis of task-induced brain stem activity indicated that both the dopaminergic and noradrenergic systems are involved in updating context representations, and that, respectively, these systems mediate a gating signal to the control network and are involved in the dynamic regulation of task engagement.

10.
Brain Behav ; 9(1): e01170, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30548825

RESUMO

INTRODUCTION: Eye movements and spatial attention are closely related, and eye-tracking can provide valuable information in research on visual attention. We investigated the pathology of overt attention in right hemisphere (RH) stroke patients differing in their severity of neglect symptoms by using eye-tracking during a dynamic attention task. METHODS: Eye movements were recorded in 26 RH stroke patients (13 with and 13 without unilateral spatial neglect, and a matched group of 26 healthy controls during a Multiple Object Tracking task. We assessed the frequency and spatial distributions of fixations, as well as frequencies of eye movements to the left and to the right side of visual space so as to investigate individuals' efficiency of visual processing, distribution of attentional processing resources, and oculomotoric orienting mechanisms. RESULTS: Both patient groups showed increased fixation frequencies compared to controls. A spatial bias was found in neglect patients' fixation distribution, depending on neglect severity (indexed by scores on the Behavioral Inattention Test). Patients with more severe neglect had more fixations within the right field, while patients with less severe neglect had more fixations within their left field. Eye movement frequencies were dependent on direction in the neglect patient group, as they made more eye movements toward the right than toward the left. CONCLUSION: The patient groups' higher fixation rates suggest that patients are generally less efficient in visual processing. The spatial bias in fixation distribution, dependent on neglect severity, suggested that patients with less severe neglect were able to use compensational mechanisms in their contralesional space. The observed relation between eye movement rates and directions observed in neglect patients provides a measure of the degree of difficulty these patients may encounter during dynamic situations in daily life and supports the idea that directional oculomotor hypokinesia may be a relevant component in this syndrome.


Assuntos
Medições dos Movimentos Oculares , Hipocinesia , Transtornos da Percepção , Acidente Vascular Cerebral , Adulto , Idoso , Movimentos Oculares , Feminino , Fixação Ocular , Humanos , Hipocinesia/diagnóstico , Hipocinesia/etiologia , Hipocinesia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Transtornos da Percepção/diagnóstico , Transtornos da Percepção/etiologia , Transtornos da Percepção/fisiopatologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia
11.
J Clin Exp Neuropsychol ; : 1-20, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30426866

RESUMO

INTRODUCTION: Unilateral spatial neglect is typically associated with a spatial attention deficit, as neglect patients fail to respond to objects in their contralesional hemispace. However, growing evidence suggests that also nonspatial attention impairments (e.g., arousal) play a role and influences the recovery from this syndrome. METHOD: Nonspatial and spatial attentional functions were assessed in 13 right-hemisphere stroke patients with neglect, 13 right-hemisphere stroke patients without neglect, and 26 healthy control participants, by investigating pupillary responses and performance on a multiple object tracking task (MOT)-that is, a dynamic task of divided attention where cognitive load can be manipulated precisely. The task was alternately presented in the left and right hemispace to assess spatial attention functioning. RESULTS: Results revealed smaller pupillary dilations in both patient groups than in controls, suggesting reduced attentional resources or arousal, and while patients without neglect and controls revealed significant effects of cognitive load on their pupillary responses, neglect patients did not. Both MOT and visual search (VS) tasks revealed spatial symptoms of neglect, while MOT performance measures additionally indicated reduced cognitive functioning in the ipsilateral hemispace. Moreover, the MOT task revealed severely reduced divided attention in neglect patients, as they only managed to track one target in the contralesional hemispace and occasionally two targets at the time in the ipsilesional hemispace. CONCLUSION: Our results suggest that a stroke may lead to reduced attentional resources. Furthermore, as neglect patients showed no indications in their pupillary responses that they were able to regulate the allocation of resources in accordance with the varying task demands, it appears they additionally had impaired mechanisms for adjusting arousal levels. Our findings suggest that neglect involves nonspatial as well as spatial attention impairments, as also ipsilesional performance was reduced in this group.

12.
Mol Psychiatry ; 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30279459

RESUMO

The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.

13.
Iperception ; 9(5): 2041669518795932, 2018 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30202509

RESUMO

Some evolutionary psychologists have hypothesized that animals have priority in human attention. That is, they should be detected and selected more efficiently than other types of objects, especially man-made ones. Such a priority mechanism should automatically deploy more attentional resources and dynamic monitoring toward animal stimuli than nonanimals. Consequently, we postulated that variations of the multiple object or identity tracking and multiple event monitoring tasks should be particularly suitable paradigms for addressing the animate monitoring hypothesis, given their dynamic properties and dependency on divided attention. We used images of animals and artifacts and found neither a substantial sign of improvement in tracking the positions associated with animal stimuli nor a significant distracting effect of animals. We also failed to observe a significant prioritization in orders of response for positions associated with animals. While we observed an advantage for animals in event monitoring, this appeared to be dependent on properties of the task, as confirmed in further experiments. Moreover, we observed a small but inconclusive advantage for animals in identity accuracy. Thus, under certain conditions, some bias toward animals could be observed, but the evidence was weak and inconclusive. To conclude, effect sizes were generally small and not conclusively in favor of the expected attentional bias for animals. We found moderate to strong evidence that images of animals do not improve positional tracking, do not act as more effective distractors, are not selected prior to artifacts in the response phase, and are not easier to monitor for changes in size.

14.
Artigo em Inglês | MEDLINE | ID: mdl-29992484

RESUMO

During the execution of a cognitive task, the brain maintains contextual information to guide behavior and achieve desired goals. The AX-Continuous Performance Task is used to study proactive versus reactive cognitive control. Young adults tend to behave proactively in standard testing conditions. However, it remains unclear how interindividual variability (e.g., in cognitive and motivational factors) may drive people into more reactive or proactive control under the same task demands. We investigated the use of control strategies in a large population of healthy young adults. We computed the proactive behavioral index and consequently divided participants into proactive, reactive, and intermediate groups. We found that reactive participants were generally slower, presented lower context sensitivity, and larger response variability. Pupillary changes and blink rate index cognitive effort allocation. We measured, concomitantly to the task, the pupil size and frequency of blinks associated with the cue maintenance and response intervals. During the cue period, nonfrequent, nontarget cues led to increased pupil dilation and number of blinks in all participants. During the response interval, we found more errors and increased pupil dilation to the probe when all participants had to overcome a response bias generated by the frequent cue. Only reactive participants showed larger response-related pupil when they had to overcome a response bias related to the frequent probe. Contrary to expectations, groups did not differ in ocular measures in the cue period. In conclusion, interindividual differences in cognitive control between healthy adults can be mapped onto different patterns of effort allocation indexed by the pupil.

15.
Twin Res Hum Genet ; 21(5): 394-397, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30001766

RESUMO

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from 'inflation in the FDR [false discovery rate]', as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not 'more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence'.

16.
Transl Psychiatry ; 8(1): 114, 2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29884845

RESUMO

Despite great interest in using magnetic resonance imaging (MRI) for studying the effects of genes on brain structure in humans, current approaches have focused almost entirely on predefined regions of interest and had limited success. Here, we used multivariate methods to define a single neuroanatomical score of how William's Syndrome (WS) brains deviate structurally from controls. The score is trained and validated on measures of T1 structural brain imaging in two WS cohorts (training, n = 38; validating, n = 60). We then associated this score with single nucleotide polymorphisms (SNPs) in the WS hemi-deleted region in five cohorts of neurologically and psychiatrically typical individuals (healthy European descendants, n = 1863). Among 110 SNPs within the 7q11.23 WS chromosomal region, we found one associated locus (p = 5e-5) located at GTF2IRD1, which has been implicated in animal models of WS. Furthermore, the genetic signals of neuroanatomical scores are highly enriched locally in the 7q11.23 compared with summary statistics based on regions of interest, such as hippocampal volumes (n = 12,596), and also globally (SNP-heritability = 0.82, se = 0.25, p = 5e-4). The role of genetic variability in GTF2IRD1 during neurodevelopment extends to healthy subjects. Our approach of learning MRI-derived phenotypes from clinical populations with well-established brain abnormalities characterized by known genetic lesions may be a powerful alternative to traditional region of interest-based studies for identifying genetic variants regulating typical brain development.

17.
Nat Commun ; 9(1): 2098, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29844566

RESUMO

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

18.
Transl Psychiatry ; 7(12): 1289, 2017 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-29249828

RESUMO

We have tested published methods for capturing allelic heterogeneity and identifying loci of joint effects to uncover more of the "hidden heritability" of schizophrenia (SCZ). We used two tools, cojo-GCTA and multi-SNP, to analyze meta-statistics from the latest genome-wide association study (GWAS) on SCZ by the Psychiatric Genomics Consortium (PGC). Stepwise regression on markers with p values <10-7 in cojo-GCTA identified 96 independent signals. Eighty-five passed the genome-wide significance threshold. Cross-validation of cojo-GCTA by CLUMP was 76%, i.e., 26 of the loci identified by the PGC using CLUMP were found to be dependent on another locus by cojo-GCTA. The overlap between cojo-GCTA and multi-SNP was better (up to 92%). Three markers reached genome-wide significance (5 × 10-8) in a joint effect model. In addition, two loci showed possible allelic heterogeneity within 1-Mb genomic regions, while CLUMP analysis had identified 16 such regions. Cojo-GCTA identified fewer independent loci than CLUMP and seems to be more conservative, probably because it accounts for long-range LD and interaction effects between markers. These findings also explain why fewer loci with possible allelic heterogeneity remained significant after cojo-GCTA analysis. With multi-SNP, 86 markers were selected at the threshold 10-7. Multi-SNP identifies fewer independent signals, due to splitting of the data and use of smaller samples. We recommend that cojo-GCTA and multi-SNP are used for post-GWAS analysis of all traits to call independent loci. We conclude that only a few loci in SCZ show joint effects or allelic heterogeneity, but this could be due to lack of power for that data set.


Assuntos
Alelos , Loci Gênicos , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Bases de Dados Genéticas , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Locos de Características Quantitativas
19.
Cell Rep ; 21(9): 2597-2613, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29186694

RESUMO

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Nootrópicos/farmacologia , Cefotaxima/análogos & derivados , Cefotaxima/farmacologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Feminino , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Sinapses/efeitos dos fármacos , Sinapses/metabolismo
20.
Nature ; 548(7665): 87-91, 2017 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-28746312

RESUMO

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark.


Assuntos
Variação Genética/genética , Genética Populacional/normas , Genoma Humano/genética , Genômica/normas , Análise de Sequência de DNA/normas , Adulto , Alelos , Criança , Cromossomos Humanos Y/genética , Dinamarca , Feminino , Haplótipos/genética , Humanos , Complexo Principal de Histocompatibilidade/genética , Masculino , Idade Materna , Taxa de Mutação , Idade Paterna , Mutação Puntual/genética , Padrões de Referência
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA