TITLE

SNPs in Multi-Species Conserved Sequences (MCS) as useful markers in association studies: a practical approach

AUTHOR(S)
McCauley, Jacob L; Kenealy, Shannon J; Margulies, Elliott H; Schnetz-Boutaud, Nathalie; Gregory, Simon G; Hauser, Stephen L; Oksenberg, Jorge R; Pericak-Vance, Margaret A; Haines, Jonathan L; Mortlock, Douglas P
PUB. DATE
January 2007
SOURCE
BMC Genomics;2007, Vol. 8, p266
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Although genes play a key role in many complex diseases, the specific genes involved in most complex diseases remain largely unidentified. Their discovery will hinge on the identification of key sequence variants that are conclusively associated with disease. While much attention has been focused on variants in protein-coding DNA, variants in noncoding regions may also play many important roles in complex disease by altering gene regulation. Since the vast majority of noncoding genomic sequence is of unknown function, this increases the challenge of identifying "functional" variants that cause disease. However, evolutionary conservation can be used as a guide to indicate regions of noncoding or coding DNA that are likely to have biological function, and thus may be more likely to harbor SNP variants with functional consequences. To help bias marker selection in favor of such variants, we devised a process that prioritizes annotated SNPs for genotyping studies based on their location within Multi-species Conserved Sequences (MCSs) and used this process to select SNPs in a region of linkage to a complex disease. This allowed us to evaluate the utility of the chosen SNPs for further association studies. Previously, a region of chromosome 1q43 was linked to Multiple Sclerosis (MS) in a genome-wide screen. We chose annotated SNPs in the region based on location within MCSs (termed MCS-SNPs). We then obtained genotypes for 478 MCS-SNPs in 989 individuals from MS families. Results: Analysis of our MCS-SNP genotypes from the 1q43 region and comparison to HapMap data confirmed that annotated SNPs in MCS regions are frequently polymorphic and show subtle signatures of selective pressure, consistent with previous reports of genome-wide variation in conserved regions. We also present an online tool that allows MCS data to be directly exported to the UCSC genome browser so that MCS-SNPs can be easily identified within genomic regions of interest. Conclusion: Our results showed that MCS can easily be used to prioritize markers for follow-up and candidate gene association studies. We believe that this novel approach demonstrates a paradigm for expediting the search for genes contributing to complex diseases.
ACCESSION #
28858886

 

Related Articles

  • Statistical Estimation of Correlated Genome Associations to a Quantitative Trait Network. Seyoung Kim; Xing, Eric P. // PLoS Genetics;Aug2009, Vol. 5 Issue 8, p1 

    Many complex disease syndromes, such as asthma, consist of a large number of highly related, rather than independent, clinical or molecular phenotypes. This raises a new technical challenge in identifying genetic variations associated simultaneously with correlated traits. In this study, we...

  • Construction of a high-density linkage map of Italian ryegrass (Lolium multiflorum Lam.) using restriction fragment length polymorphism, amplified fragment length polymorphism, and telomeric repeat associated sequence markers. Inoue, Maiko; Zhensheng Gao; Hirata, Mariko; Fujimori, Masahiro; Hongwei Cai // Genome;Feb2004, Vol. 47 Issue 1, p57 

    To construct a high-density molecular linkage map of Italian ryegrass (Lolium multiflorum Lam.), we used a two-way pseudo-testcross F1 population consisting of 82 individuals to analyze three types of markers: restriction fragment length polymorphism markers, which we detected by using genomic...

  • An interspecific linkage map of SSR and intronic polymorphism markers in tomato. Shirasawa, Kenta; Asamizu, Erika; Fukuoka, Hiroyuki; Ohyama, Akio; Sato, Shusei; Nakamura, Yasukazu; Tabata, Satoshi; Sasamoto, Shigemi; Wada, Tsuyuko; Kishida, Yoshie; Tsuruoka, Hisano; Fujishiro, Tsunakazu; Yamada, Manabu; Isobe, Sachiko // Theoretical & Applied Genetics;Aug2010, Vol. 121 Issue 4, p731 

    Despite the collection and availability of abundant tomato genome sequences, PCR-based markers adapted to large scale analysis have not been developed in tomato species. Therefore, using public genome sequence data in tomato, we developed three types of DNA markers: expressed sequence tag...

  • Genome-wide association analysis of GAW17 data using an empirical Bayes variable selection. Pungpapong, Vitara; Wang, Libo; Lin, Yanzhu; Zhang, Dabao; Zhang, Min // BMC Proceedings;2011 Supplement 9, Vol. 5 Issue Suppl 9, p1 

    Next-generation sequencing technologies enable us to explore rare functional variants. However, most current statistical techniques are too underpowered to capture signals of rare variants in genome-wide association studies. We propose a supervised coalescing of single-nucleotide polymorphisms...

  • Animal Markers Assisted Selection in South America: A Point of View. Rogberg-Muñoz, Andrés; Prando, Alberto; Baldo, Andrés; Peral-García, Pilar; Giovambattista, Guillermo // Recent Patents on DNA & Gene Sequences;Jun2008, Vol. 2 Issue 3, p133 

    Genetic identification has been continuously evolving during the last century. The recent development of whole-genome projects allowed the discovery and characterization of a large number of single nucleotide polymorphisms (SNP). A number of high-throughput DNA methods has decreased the cost of...

  • STR markers for detecting heterogeneity in Indian population. Jain, Shalu; Panigrahi, Inusha; Sheth, Jayesh; Agarwal, Sarita // Molecular Biology Reports;Jan2012, Vol. 39 Issue 1, p461 

    Short tandem repeats are highly polymorphic sequences of nucleotides, which are abundant in eukaryotic genome. They form approximately 3% of the total human genome and occur on average in every 10, 000 nucleotides. Due to their small dimension, low mutation, and high level of polymorphism, these...

  • Confirmation and fine-mapping of a major QTL for resistance to infectious pancreatic necrosis in Atlantic salmon (Salmo salar): population-level associations between markers and trait. Moen, Thomas; Baranski, Matthew; Sonesson, Anna K.; Kjøglum, Sissel // BMC Genomics;2009, Vol. 10, p368 

    Background: Infectious pancreatic necrosis (IPN) is one of the most prevalent and economically devastating diseases in Atlantic salmon (Salmo salar) farming worldwide. The disease causes large mortalities at both the fry- and post-smolt stages. Family selection for increased IPN resistance is...

  • Development and implementation of high-throughput SNP genotyping in barley. Close, Timothy J.; Bhat, Prasanna R.; Lonardi, Stefano; Yonghui Wu; Rostoks, Nils; Ramsay, Luke; Druka, Arnis; Stein, Nils; Svensson, Jan T.; Wanamaker, Steve; Bozdag, Serdar; Roose, Mikeal L.; Moscou, Matthew J.; Shiaoman Chao; Varshney, Rajeev K.; Szűcs, Péter; Sato, Kazuhiro; Hayes, Patrick M.; Matthews, David E.; Kleinhofs, Andris // BMC Genomics;2009, Vol. 10, p582 

    Background: High density genetic maps of plants have, nearly without exception, made use of marker datasets containing missing or questionable genotype calls derived from a variety of genic and non-genic or anonymous markers, and been presented as a single linear order of genetic loci for each...

  • Using linkage analysis of large pedigrees to guide association analyses. Choi, Seung-Hoan; Chunyu Liu; Dupuis, Josée; Logue, Mark W.; Gyungah Jun // BMC Proceedings;2011 Supplement 9, Vol. 5 Issue Suppl 9, p1 

    To date, genome-wide association studies have yielded discoveries of common variants that partly explain familial aggregation of diseases and traits. Researchers are now turning their attention to less common variants because the price of sequencing has dropped drastically. However, because...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics