Browsing by Author "Choi, Jungmin"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus
    (CELL PRESS, 2018-01-01) Furey, Charuta Gavankar; Choi, Jungmin; Jin, Sheng Chih; Zeng, Xue; Timberlake, Andrew T.; Nelson-Williams, Carol; Mansuri, M. Shahid; Lu, Qiongshi; Duran, Daniel; Panchagnula, Shreyas; Allocco, August; Karimy, Jason K.; Khanna, Arjun; Gaillard, Jonathan R.; DeSpenza, Tyrone; Antwi, Prince; Loring, Erin; Butler, William E.; Smith, Edward R.; Warf, Benjamin C.; Strahle, Jennifer M.; Limbrick, David D.; Storm, Phillip B.; Heuer, Gregory; Jackson, Eric M.; Iskandar, Bermans J.; Johnston, James M.; Tikhonova, Irina; Castaldi, Christopher; Lopez-Giraldez, Francesc; Bjornson, Robert D.; Knight, James R.; Bilguvar, Kaya; Mane, Shrikant; Alper, Seth L.; Haider, Shozeb; Guclu, Bulent; Bayri, Yasar; Sahin, Yener; Apuzzo, Michael L. J.; Duncan, Charles C.; DiLuna, Michael L.; Gunel, Murat; Lifton, Richard P.; Kahle, Kristopher T.
    Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 x 10(-7)), SMARCC1 (p = 8.15 x 10(-10)), and PTCH1 (p = 1.06 x 10(-6)). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 x 10(-4)). Together, these probands account for similar to 10\% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications.
  • No Thumbnail Available
    Item
    The genetic structure of the Turkish population reveals high levels of variation and admixture
    (NATL ACAD SCIENCES, 2021-01-01) Kars, M. Ece; Basak, A. Nazli; Onat, O. Emre; Bilguvar, Kaya; Choi, Jungmin; Itan, Yuval; Caglar, Caner; Palvadeau, Robin; Casanova, Jean-Laurent; Cooper, David N.; Stenson, Peter D.; Yavuz, Alper; Bulus, Hakan; Gunel, Murat; Friedman, Jeffrey M.; Ozcelik, Tayfun
    The construction of population-based variomes has contributed substantially to our understanding of the genetic basis of human inherited disease. Here, we investigated the genetic structure of Turkey from 3,362 unrelated subjects whose whole exomes (n = 2,589) or whole genomes (n = 773) were sequenced to generate a Turkish (TR) Variome that should serve to facilitate disease gene discovery in Turkey. Consistent with the history of present-day Turkey as a crossroads between Europe and Asia, we found extensive admixture between Balkan, Caucasus, Middle Eastern, and European populations with a closer genetic relationship of the TR population to Europeans than hitherto appreciated. We determined that 50\% of TR individuals had high inbreeding coefficients (>= 0.0156) with runs of homozygosity longer than 4 Mb being found exclusively in the TR population when compared to 1000 Genomes Project populations. We also found that 28\% of exome and 49\% of genome variants in the very rare range (allele frequency < 0.005) are unique to the modern TR population. We annotated these variants based on their functional consequences to establish a TR Variome containing alleles of potential medical relevance, a repository of homozygous loss-of-function variants and a TR reference panel for genotype imputation using high-quality haplotypes, to facilitate genome-wide association studies. In addition to providing information on the genetic structure of the modern TR population, these data provide an invaluable resource for future studies to identify variants that are associated with specific phenotypes as well as establishing the phenotypic consequences of mutations in specific genes.