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Yanggu, South Korea

Yoo H.J.,Seoul National University | Kim K.,Korea Research Institute of Bioscience and Biotechnology | Kim K.,Ajou University | Kim I.H.,Seoul National University | And 6 more authors.
International Journal of Molecular Sciences | Year: 2015

Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in 125,000–720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES) to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS) and Autism diagnostic interview revised (ADI-R) to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

Kim J.-H.,Korean International Vaccine Institute | Kim J.-H.,Simulacre Modeling Group
Acta Biotheoretica | Year: 2015

Most mathematical models used to examine the role of different stages of human immunodeficiency virus (HIV) infection unrealistically assume that HIV is transmitted through one-off contacts or that transmission rates are the same between males and females. We sought to examine whether inferences from previous models are robust to the relaxation of those unrealistic assumptions. We developed a model of HIV transmissions through sexual partnerships assuming that (1) sexual partnerships have variable duration, (2) sexual partnerships are concurrent, and (3) the male-to-female transmission rate is higher than the female-to-male transmission rate, with a focus on the third assumption. Assuming a higher rate for male-to-female than female-to-male transmissions decreases the overall transmission of HIV but increases the equilibrium fraction of transmissions during primary HIV infection (PHI) in long-term partnerships, compared to the case where transmission rates are assumed to be symmetric between males an females. Previous modeling studies that assume symmetric transmission rates between males and females may have overestimated the overall spread of HIV, but underestimated the relative contribution of PHI. To make robust inferences on the role of different stages of HIV infection in the sexual spread of HIV, models should take into account that transmission rates may be asymmetric by sex. © 2014, Springer Science+Business Media Dordrecht.

Kim J.-H.,Korean International Vaccine Institute | Kim J.-H.,Simulacre Modeling Group | Rho S.-H.,Simulacre Modeling Group
Journal of Theoretical Biology | Year: 2015

One drawback of oral polio vaccine (OPV) is the potential reversion to more transmissible, virulent circulating vaccine-derived polioviruses (cVDPVs), which may cause outbreaks of paralytic poliomyelitis. Previous modeling studies of the transmission of cVDPVs assume an unrealistic homogeneous mixing of the population and/or ignore that OPV viruses and cVDPVs compete for susceptibles, which we show is a key to understanding the dynamics of the transmission of cVDPVs. We examined the transmission of OPV viruses and cVDPVs on heterogeneous, dynamic contact networks using differential equation-based and individual-based models. Despite the lower transmissibility, OPV viruses may outcompete more transmissible cVDPVs in the short run by spreading extensively before cVDPVs emerge. If viruses become endemic, however, cVDPVs eventually dominate and force OPV viruses to extinction. This study improves our understanding of the emergence of cVDPVs and helps develop more detailed models to plan a policy to control paralytic polio associated with the continued use of OPV in many countries. © 2014 Elsevier Ltd.

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