Functional interpretation of non‐coding sequence variation: Concepts and challenges

Paul, Dirk S.; Soranzo, Nicole; Beck, Stephan

doi:10.1002/bies.201300126

Cited by 54 publications

(39 citation statements)

References 92 publications

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“…Determining the biological ramifications of noncoding variation will become increasingly important as whole-genome sequencing becomes routine, and it is already crucial in interpreting association studies because the majority of common variants lie outside protein-coding regions (117). This is true for most variants in genes such as KIAA0319, DCDC2, DYX1C1, ROBO1, ATP2C2, CMIP, and CNTNAP2 that have been associated with language-related phenotypes.…”

Section: Identifying Variants Of Functional Significancementioning

confidence: 98%

Understanding Language from a Genomic Perspective

2015

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Language is a defining characteristic of the human species, but its foundations remain mysterious. Heritable disorders offer a gateway into biological underpinnings, as illustrated by the discovery that FOXP2 disruptions cause a rare form of speech and language impairment. The genetic architecture underlying language-related disorders is complex, and although some progress has been made, it has proved challenging to pinpoint additional relevant genes with confidence. Next-generation sequencing and genome-wide association studies are revolutionizing understanding of the genetic bases of other neurodevelopmental disorders, like autism and schizophrenia, and providing fundamental insights into the molecular networks crucial for typical brain development. We discuss how a similar genomic perspective, brought to the investigation of language-related phenotypes, promises to yield equally informative discoveries. Moreover, we outline how follow-up studies of genetic findings using cellular systems and animal models can help to elucidate the biological mechanisms involved in the development of brain circuits supporting language.

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Section: Identifying Variants Of Functional Significancementioning

confidence: 98%

Understanding Language from a Genomic Perspective

2015

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“…Thus, the molecular function of SNPs needs to be interpreted in other ways. 6,7 In recent years, the Encyclopedia of DNA Elements (ENCODE) project and the Functional ANnoTation Of the Mammalian genome (FANTOM) consortium have advanced our understanding on the principles of genome organization and function, and have identified a large number of novel transcripts, namely noncoding RNAs (ncRNAs). 8 The ncRNAs were previously thought as transcriptional noises from junk DNA, but now they consist of a class of functional RNA molecules that do not translate into proteins.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA variations in cardiometabolic diseases

Dechamethakun

Muramatsu

2016

J Hum Genet

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Cardiometabolic diseases are characterized as a combination of multiple risk factors for cardiovascular disease (CVD) and metabolic diseases including diabetes mellitus, dyslipidemia, hypertension and abdominal obesity. This cluster of abnormalities individually and interdependently leads to atherosclerosis and CVD morbidity and mortality. In the past decade, genome-wide association studies (GWASs) have identified a series of cardiometabolic disease-associated variants that can collectively explain a small proportion of the variability. Intriguingly, the susceptibility variants imputed from GWASs usually do not reside in the coding regions, suggesting a crucial role of the noncoding elements of the genome. In recent years, emerging evidence suggests that noncoding RNA (ncRNA) is functional for physiology and pathophysiology of human diseases. These include microRNAs and long noncoding RNAs (lncRNAs) that are now implicated in human diseases. The ncRNAs can interact with each other and with proteins, to interfere gene expressions, leading to the development of many human disorders. Although evidence suggests the functional role of lncRNAs in cardiometabolic traits, the molecular mechanisms of gene regulation underlying cardiometabolic diseases remain to be better defined. Here, we summarize the recent discoveries of lncRNA variations in the context of cardiometabolic diseases.

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“…This finding suggests that crosstalk between epigenetic regulatory mechanisms (Table 1) and genetic variants present at these sites, which may represent noncoding RNA (ncRNA) genes, promoters, enhancers, and other functional genomic elements, underpins the onset, progression, and therapeutic responsiveness of these disorders. Thus, scientific and technological innovations are now focused on interrogating these additional layers of biological complexity [13].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Mechanisms Underlying the Pathogenesis of Neurogenetic Diseases

Qureshi

Mehler

2014

Neurotherapeutics

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There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other healthrelated phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

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Functional interpretation of non‐coding sequence variation: Concepts and challenges

Cited by 54 publications

References 92 publications

Understanding Language from a Genomic Perspective

Understanding Language from a Genomic Perspective

Long noncoding RNA variations in cardiometabolic diseases

Epigenetic Mechanisms Underlying the Pathogenesis of Neurogenetic Diseases

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