Person:
Chun, Sung

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Chun

First Name

Sung

Name

Chun, Sung
Author's Publications: search.filters.isAuthorOfPublication.91524e99-b823-4eae-991b-9d99e4e130a6

Search Results

Now showing 1 - 4 of 4
  • Thumbnail Image
    Publication
    Limited statistical evidence for shared genetic effects of eQTLs and autoimmune disease-associated loci in three major immune cell types
    (2017) Chun, Sung; Casparino, Alexandra; Patsopoulos, Nikolaos; Croteau-Chonka, Damien; Raby, Benjamin; De Jager, Philip; Sunyaev, Shamil; Cotsapas, Chris
  • Thumbnail Image
    Publication
    Genes with monoallelic expression contribute disproportionately to genetic diversity in humans
    (2016) Savova, Virginia; Chun, Sung; Sohail, Mashaal; McCole, Ruth; Witwicki, Robert; Gai, Lisa; Lenz, Tobias L.; Wu, C.-ting; Sunyaev, Shamil; Gimelbrant, Alexander
    An unexpectedly large number of human autosomal genes are subject to monoallelic expression (MAE). Our analysis of 4,227 such genes reveals surprisingly high genetic variation across human populations. This increased diversity is unlikely to reflect relaxed purifying selection. Remarkably, MAE genes exhibit elevated recombination rate and increased density of hypermutable sequence contexts. However, these factors do not fully account for the increased diversity. We find that the elevated nucleotide diversity of MAE genes is also associated with greater allelic age: their variants tend to be older and are enriched in polymorphisms shared with Neanderthals and chimpanzees. Both synonymous and nonsynonymous alleles in MAE genes have elevated average population frequencies. We also observed strong enrichment of the MAE signature among genes reported to evolve under balancing selection. We propose that an important biological function of widespread MAE might be generation of cell-to-cell heterogeneity; the increased genetic variation contributes to this heterogeneity.
  • Thumbnail Image
    Publication
    Genome-wide patterns and properties of de novo mutations in humans
    (2015) Francioli, Laurent C.; Polak, Paz P.; Koren, Amnon; Menelaou, Androniki; Chun, Sung; Renkens, Ivo; van Duijn, Cornelia M.; Swertz, Morris; Wijmenga, Cisca; van Ommen, Gertjan; Slagboom, P. Eline; Boomsma, Dorret I.; Ye, Kai; Guryev, Victor; Arndt, Peter F.; Kloosterman, Wigard P.; de Bakker, Paul I. W.; Sunyaev, Shamil
    Mutations create variation in the population, fuel evolution, and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect 1–10. Here, we analyze 11,020 de novo mutations from whole-genomes of 250 families. We show that de novo mutations in offspring of older fathers are not only more numerous 11–13 but also occur more frequently in early-replicating, genic regions. Functional regions exhibit higher mutation rates due to CpG dinucleotides and reveal signatures of transcription-coupled repair, while mutation clusters with a unique signature point to a novel mutational mechanism. Mutation and recombination rates independently associate with nucleotide diversity, and regional variation in human-chimpanzee divergence is only partly explained by mutation rate heterogeneity. Finally, we provide a genome-wide mutation rate map for medical and population genetics applications. Our results reveal novel insights and refine long-standing hypotheses about human mutagenesis.
  • Thumbnail Image
    Publication
    Using whole-genome sequences of the LG/J and SM/J inbred mouse strains to prioritize quantitative trait genes and nucleotides
    (BioMed Central, 2015) Nikolskiy, Igor; Conrad, Donald F; Chun, Sung; Fay, Justin C; Cheverud, James M; Lawson, Heather A
    Background: The laboratory mouse is the most commonly used model for studying variation in complex traits relevant to human disease. Here we present the whole-genome sequences of two inbred strains, LG/J and SM/J, which are frequently used to study variation in complex traits as diverse as aging, bone-growth, adiposity, maternal behavior, and methamphetamine sensitivity. Results: We identified small nucleotide variants (SNVs) and structural variants (SVs) in the LG/J and SM/J strains relative to the reference genome and discovered novel variants in these two strains by comparing their sequences to other mouse genomes. We find that 39% of the LG/J and SM/J genomes are identical-by-descent (IBD). We characterized amino-acid changing mutations using three algorithms: LRT, PolyPhen-2 and SIFT. We also identified polymorphisms between LG/J and SM/J that fall in regulatory regions and highly informative transcription factor binding sites (TFBS). We intersected these functional predictions with quantitative trait loci (QTL) mapped in advanced intercrosses of these two strains. We find that QTL are both over-represented in non-IBD regions and highly enriched for variants predicted to have a functional impact. Variants in QTL associated with metabolic (231 QTL identified in an F16 generation) and developmental (41 QTL identified in an F34 generation) traits were interrogated and we highlight candidate quantitative trait genes (QTG) and nucleotides (QTN) in a QTL on chr13 associated with variation in basal glucose levels and in a QTL on chr6 associated with variation in tibia length. Conclusions: We show how integrating genomic sequence with QTL reduces the QTL search space and helps researchers prioritize candidate genes and nucleotides for experimental follow-up. Additionally, given the LG/J and SM/J phylogenetic context among inbred strains, these data contribute important information to the genomic landscape of the laboratory mouse. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1592-3) contains supplementary material, which is available to authorized users.