Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24287333
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Using chromatin marks to interpret and localize genetic associations to complex
human traits and diseases
#MMPMID24287333
Trynka G
; Raychaudhuri S
Curr Opin Genet Dev
2013[Dec]; 23
(6
): 635-41
PMID24287333
show ga
While studies to associate genomic variants to complex traits have gradually
become increasingly productive, the molecular mechanisms that underlie these
associations are rarely understood. Because only a small fraction of
trait-associated variants can be linked to coding sequences, investigators have
speculated that many of the underlying causal alleles influence non-coding gene
regulatory sites. Recent studies have successfully identified examples of
mechanisms for non-coding alleles at individual loci. Now, genome-wide chromatin
assays have resulted in maps of dozens of genomic annotations of the non-coding
genome across multiple different tissues, cell types and cell lines. This gives a
tremendous opportunity to integrate these annotations with complex trait signals
to globally interpret associated variants, and prioritize likely causal alleles.
Here, we review the examples of mechanisms by which non-coding, common alleles
result in phenotypes. We discuss the efforts to integrate common trait-associated
variants with genomic annotations. Finally, we highlight some caveats of these
approaches and outline future directions for improvement.
|Alleles
[MESH]
|Chromatin/*genetics
[MESH]
|Chromosome Mapping/*methods
[MESH]
|Genetic Predisposition to Disease/*genetics
[MESH]
free
free
free
