Fine-scale detection of population-specific linkage disequilibrium using haplotype entropy in the human genome

Mizuno, Hideaki; Atwal, Gurinder; Haijian Wang; Levine, Arnold J.; Vazquez, Alexei
January 2010
BMC Genetics;2010, Vol. 11, p27
Academic Journal
Background: The creation of a coherent genomic map of recent selection is one of the greatest challenges towards a better understanding of human evolution and the identification of functional genetic variants. Several methods have been proposed to detect linkage disequilibrium (LD), which is indicative of natural selection, from genome-wide profiles of common genetic variations but are designed for large regions. Results: To find population-specific LD within small regions, we have devised an entropy-based method that utilizes differences in haplotype frequency between populations. The method has the advantages of incorporating multilocus association, conciliation with low allele frequencies, and independence from allele polarity, which are ideal for short haplotype analysis. The comparison of HapMap SNPs data from African and Caucasian populations with a median resolution size of ∼23 kb gave us novel candidates as well as known selection targets. Enrichment analysis for the yielded genes showed associations with diverse diseases such as cardiovascular, immunological, neurological, and skeletal and muscular diseases. A possible scenario for a selective force is discussed. In addition, we have developed a web interface (ENIGMA, available at http://gibk21.bse.kyutech.ac.jp/ENIGMA/index.html), which allows researchers to query their regions of interest for population-specific LD. Conclusion: The haplotype entropy method is powerful for detecting population-specific LD embedded in short regions and should contribute to further studies aiming to decipher the evolutionary histories of modern humans.


Related Articles

  • SNPs on chromosome 5p15.3 associated with myocardial infarction in Japanese population. Aoki, Asako; Ozaki, Kouichi; Sato, Hiroshi; Takahashi, Atsushi; Kubo, Michiaki; Sakata, Yasuhiko; Onouchi, Yoshihiro; Kawaguchi, Takahisa; Lin, Tsung-Hsien; Takano, Hitoshi; Yasutake, Masahiro; Hsu, Po-Chao; Ikegawa, Shiro; Kamatani, Naoyuki; Tsunoda, Tatsuhiko; Juo, Suh-Hang H; Hori, Masatsugu; Komuro, Issei; Mizuno, Kyoichi; Nakamura, Yusuke // Journal of Human Genetics;Jan2011, Vol. 56 Issue 1, p47 

    Myocardial infarction (MI) occurs as the result of complex interactions of multiple genetic and environmental factors. By conducting a genome wide association study in a Japanese population using 210 785 single nucleotide polymorphism (SNP) markers, we identified a novel susceptible locus for MI...

  • Finding disease genes: a fast and flexible approach for analyzing high-throughput data. Stewart, William C. L.; Drill, Esther N.; Greenberg, David A. // European Journal of Human Genetics;Oct2011, Vol. 19 Issue 10, p1090 

    Linkage disequilibrium (LD) is the non-random distribution of alleles across the genome, and it can create serious problems for modern linkage studies. In particular, computational feasibility is often obtained at the expense of power, precision, and/or accuracy. In our new approach, we combine...

  • Utilizing linkage disequilibrium information from Indian Genome Variation Database for mapping mutations: SCA12 case study. BAHL, SAMIRA; AHMED, IKHLAK; MUKERJI, MITALI // Journal of Genetics;Apr2009, Vol. 88 Issue 1, p55 

    Stratification in heterogeneous populations poses an enormous challenge in linkage disequilibrium (LD) based identification of causal loci using surrogate markers. In this study, we demonstrate the enormous potential of endogamous Indian populations for mapping mutations in candidate genes using...

  • Genome-wide analysis of zygotic linkage disequilibrium and its components in crossbred cattle. Qi Jiang1; Zhiquan Wang1; Moore1, Stephen S.; Rong-Cai Yang1 // BMC Genetics;2012, Vol. 13 Issue 1, p65 

    Background: Linkage disequilibrium (LD) between genes at linked or independent loci can occur at gametic and zygotic levels known asgametic LD and zygotic LD, respectively. Gametic LD is well known for its roles in fine-scale mapping of quantitative trait loci, genomic selection and evolutionary...

  • Linkage disequilibrium and age of HLA region SNPs in relation to classic HLA gene alleles within Europe. Evseeva, Irina; Nicodemus, Kristin K.; Bonilla, Carolina; Tonks, Susan; Bodmer, Walter F. // European Journal of Human Genetics;Aug2010, Vol. 18 Issue 8, p924 

    The HLA region on chromosome 6 is gene-rich and under selective pressure because of the high proportion of immunity-related genes. Linkage disequilibrium (LD) patterns and allele frequencies in this region are highly differentiated across broad geographical populations, making it a region of...

  • Estimating linkage disequilibria. Barton, N. H. // Heredity;Feb2011, Vol. 106 Issue 2, p205 

    In this article, the author analyzes the linkage disequilibrium (LD) in population genetics. The author states that linkage disequilibria is derived from non-random association of alleles at two or more loci which are broken down by recombination at the same or different chromosomes which...

  • Isolated populations as treasure troves in genetic epidemiology: the case of the Basques. Garagnani, Paolo; Laayouni, Hafid; González-Neira, Anna; Sikora, Martin; Luiselli, Donata; Bertranpetit, Jaume; Calafell, Francesc // European Journal of Human Genetics;Nov2009, Vol. 17 Issue 11, p1490 

    The Basques are a culturally isolated population, living across the western border between France and Spain and speaking a non-Indo-European language. They show outlier allele frequencies in the ABO, RH, and HLA loci. To test whether Basques are a genetic isolate with the features that would...

  • Comparison of multimarker logistic regression models, with application to a genomewide scan of schizophrenia. Wason, James M. S.; Dudbridge, Frank // BMC Genetics;2010, Vol. 11, p80 

    Background: Genome-wide association studies (GWAS) are a widely used study design for detecting genetic causes of complex diseases. Current studies provide good coverage of common causal SNPs, but not rare ones. A popular method to detect rare causal variants is haplotype testing. A disadvantage...

  • Development of 30 Novel Polymorphic Expressed Sequence Tags (EST)-Derived Microsatellite Markers for the Miiuy Croaker, Miichthys miiuy. Tianjun Xu; Dianqiao Sun; Yuena Sun; Rixin Wang // International Journal of Molecular Sciences;Jun2011, Vol. 12 Issue 6, p4021 

    Expressed sequence tags (ESTs) can be used to identify microsatellite markers. We developed 30 polymorphic microsatellite markers from 5053 ESTs of the Miichthys miiuy. Out of 123 EST derived microsatellites for which PCR primers were designed, 30 loci were polymorphic in 30 individuals from a...


Read the Article


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

Try another library?
Sign out of this library

Other Topics