|Title||Interpreting noncoding genetic variation in complex traits and human disease.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Ward, LD, Kellis, M|
|Date Published||2012 Nov|
|Keywords||complex disease, gene regulation|
Association studies provide genome-wide information about the genetic basis of complex disease, but medical research has focused primarily on protein-coding variants, owing to the difficulty of interpreting noncoding mutations. This picture has changed with advances in the systematic annotation of functional noncoding elements. Evolutionary conservation, functional genomics, chromatin state, sequence motifs and molecular quantitative trait loci all provide complementary information about the function of noncoding sequences. These functional maps can help with prioritizing variants on risk haplotypes, filtering mutations encountered in the clinic and performing systems-level analyses to reveal processes underlying disease associations. Advances in predictive modeling can enable data-set integration to reveal pathways shared across loci and alleles, and richer regulatory models can guide the search for epistatic interactions. Lastly, new massively parallel reporter experiments can systematically validate regulatory predictions. Ultimately, advances in regulatory and systems genomics can help unleash the value of whole-genome sequencing for personalized genomic risk assessment, diagnosis and treatment.
|Alternate Journal||Nat. Biotechnol.|
Interpreting noncoding genetic variation in complex traits and human disease.
For years, I've worked on their bones. Now I'm working on their genes. Read more about the science studying these ancient people.
From a finger bone of an ancient human came the record of a completely unexpected population. My lab is working on the science of the Denisova genome.
The advent of agriculture caused natural selection to speed up greatly in humans. We're uncovering some of the ways that populations have rapidly changed during the last 10,000 years.