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Laying a solid foundation for Manhattan : 'setting the functional basis for the post-GWAS era' / by Xiaoyang Zhang

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Author	Zhang, Xiaoyang.
Title	Laying a solid foundation for Manhattan : 'setting the functional basis for the post-GWAS era' / by Xiaoyang Zhang
Date	2013
Abstract	Genome-wide association studies (GWAS) have identified more than 8,900 genetic variants, mainly single nucleotide polymorphisms (SNPs), associated with hundreds of human traits and diseases, which define risk-associated loci (Hindorff et al., 2012 Hindorff et al., 2009). Previous efforts focusing on risk loci mapping to coding regions have reported that genetic risk-variants can affect protein sequence, transcriptional rate and alternative splicing to influence protein function (Gregory et al., 2012 Kimchi-Sarfaty et al., 2007 Kooner et al., 2008). However, the functional nature of risk-associated loci remains for the most part unknown mainly due to the fact that few fall within coding sequences. The vast majority of risk-associated loci map to non-coding intergenic and intronic regions (The 1000 Genome Project Consortium, 2010 Frazer et al., 2009). Recent largescale efforts of genome-wide annotation for transcribed and protein associated genomic regions revealed that over 80% of the human genome is functional (Dunham et al. 2012). This annotation has contributed to post-GWAS studies by facilitating the identification of the functional targets for risk-associated loci. Our studies reveal that genetic variants within risk-associated loci from the noncoding regions can modulate the activity of cis-regulatory elements, such as enhancers, by directly modulating the binding affinity of transcription factors. Here, we present our recent findings and discuss their implication for the post-GWAS era.
Description	vi, 115 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	Michae D. Cole, Mathieu Lubien, Jason H. Moore, Pierre-Etienne Jacques
College	Dartmouth Medical School. Department of Genetics.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1018

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