Dataset Information

In The Blood: Connecting Variant to Function In Human Hematopoiesis.

ABSTRACT: Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with a range of human diseases and traits. However, understanding the mechanisms by which these genetic variants have an impact on associated diseases and traits, often referred to as the variant-to-function (V2F) problem, remains a significant hurdle. Solving the V2F challenge requires us to identify causative genetic variants, relevant cell types/states, target genes, and mechanisms by which variants can cause diseases or alter phenotypic traits. We discuss emerging functional approaches that are being applied to tackle the V2F problem for blood cell traits, illuminating how human genetic variation can impact on key mechanisms in hematopoiesis, as well as highlighting future prospects for this nascent field.

SUBMITTER: Nandakumar SK

PROVIDER: S-EPMC7363574 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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In The Blood: Connecting Variant to Function In Human Hematopoiesis.

Nandakumar Satish K SK Liao Xiaotian X Sankaran Vijay G VG

Trends in genetics : TIG 20200610 8

Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with a range of human diseases and traits. However, understanding the mechanisms by which these genetic variants have an impact on associated diseases and traits, often referred to as the variant-to-function (V2F) problem, remains a significant hurdle. Solving the V2F challenge requires us to identify causative genetic variants, relevant cell types/states, target genes, and mechanisms by which variant ...[more]

PMID: 32534791

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Project description:A successful reciprocal evaluation of social signals serves as a prerequisite for social coherence and empathy. In a previous fMRI study we studied naturalistic communication situations by presenting video clips to our participants and recording their behavioral responses regarding empathy and its components. In two conditions, all three channels transported congruent emotional or neutral information, respectively. Three conditions selectively presented two emotional channels and one neutral channel and were thus bimodally emotional. We reported channel-specific emotional contributions in modality-related areas, elicited by dynamic video clips with varying combinations of emotionality in facial expressions, prosody, and speech content. However, to better understand the underlying mechanisms accompanying a naturalistically displayed human social interaction in some key regions that presumably serve as specific processing hubs for facial expressions, prosody, and speech content, we pursued a reanalysis of the data. Here, we focused on two different descriptions of temporal characteristics within these three modality-related regions [right fusiform gyrus (FFG), left auditory cortex (AC), left angular gyrus (AG) and left dorsomedial prefrontal cortex (dmPFC)]. By means of a finite impulse response (FIR) analysis within each of the three regions we examined the post-stimulus time-courses as a description of the temporal characteristics of the BOLD response during the video clips. Second, effective connectivity between these areas and the left dmPFC was analyzed using dynamic causal modeling (DCM) in order to describe condition-related modulatory influences on the coupling between these regions. The FIR analysis showed initially diminished activation in bimodally emotional conditions but stronger activation than that observed in neutral videos toward the end of the stimuli, possibly by bottom-up processes in order to compensate for a lack of emotional information. The DCM analysis instead showed a pronounced top-down control. Remarkably, all connections from the dmPFC to the three other regions were modulated by the experimental conditions. This observation is in line with the presumed role of the dmPFC in the allocation of attention. In contrary, all incoming connections to the AG were modulated, indicating its key role in integrating multimodal information and supporting comprehension. Notably, the input from the FFG to the AG was enhanced when facial expressions conveyed emotional information. These findings serve as preliminary results in understanding network dynamics in human emotional communication and empathy.

Dataset Information

In The Blood: Connecting Variant to Function In Human Hematopoiesis.

Publications

In The Blood: Connecting Variant to Function In Human Hematopoiesis.

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