Direct-to-consumer genetic testing: advantages and pitfalls

Oh, Bermseok Korea Genome Organization 2019 Genomics & informatics Vol.17 No.3

Differential Expression of Spin Transcripts: Oocyte and Somatic Types

Oh, Bermseok,Hwang, Sue-Yun,Solter, Davor,Knowles, Barbara The Korean Society for Integrative Biology 2001 Korean journal of biological sciences Vol.5 No.1

Spin is an abundant maternal transcript comprising up to 0.2% of the total mRNA stock in mouse oocyte, whose protein product is associated with the meiotic spindle. We have identified a new isoform of Spin transcript containing a distinct 5'-untranslated region and the N-terminus of encoded protein. Northern blot and RT-PCR analysis showed that the new isoform is expressed in embryos and most of adult tissues, while the previously identified transcript is expressed solely in mouse oocyte. We thus designated these two Spin isoforms as somatic type and oocyte type, respectively. To investigate the underlying mechanism for the differential expression, genomic structure of Spin was examined. Spin exists as multiple copies in the genome, some of which appears to be pseudogenes, and characterization of Spin genomic clones indicates that oocyte- and somatic-isoforms were generated by alternative splicing. The complex organization of Spin genomic locus and its multifaceted control of expression provide a good model to study the molecular mechanisms of elaborate genome usage in mammals.

MediScore: MEDLINE-based Interactive Scoring of Gene and Disease Associations

Cho, Hye-Young,Oh, Bermseok,Lee, Jong-Keuk,Kim, Kuchan,Koh, InSong Korea Genome Organization 2004 Genomics & informatics Vol.2 No.3

MediScore is an information retrieval system, which helps to search for the set of genes associated with a specific disease or the set of diseases associated with a specific gene. Despite recent improvement of natural language processing (NLP) and other text mining approaches to search for disease associated genes, many false positive results come out due to diversity of exceptional cases as well as ambiguities in gene names. In order to overcome the weak points of current text mining approaches, MediScore introduces statistical normalization based on binomial to normal distribution approximation which corrects inaccurate scores caused by common words not representing genes and interactive rescoring by the user to remove the false positive results. Interactive rescoring includes individual alias scoring for each gene to remove false gene synonyms, referring MEDLINE abstracts, and cross referencing between OMIM and other related information.

A novel single nucleotide polymorphism of <i>INSR</i> gene for polycystic ovary syndrome

Lee, Eung-Ji,Oh, Bermseok,Lee, Jong-Young,Kimm, Kuchan,Lee, Sook-Hwan,Baek, Kwang-Hyun Elsevier 2008 Fertility and sterility Vol.89 No.5

<P><B>Objective</B></P> <P>To investigate several single nucleotide polymorphisms (SNPs) in the insulin receptor (<I>INSR</I>) gene that have significant associations with pathogenesis of polycystic ovary syndrome (PCOS) in a Korean population.</P> <P><B>Design</B></P> <P>Case-control study.</P> <P><B>Setting</B></P> <P>University-based hospital.</P> <P><B>Patient(s)</B></P> <P>134 patients with PCOS and 100 healthy women as controls.</P> <P><B>Intervention(s)</B></P> <P>All exons of <I>INSR</I> in DNA samples from 100 healthy women and 134 women with PCOS were sequenced and compared.</P> <P><B>Main Outcome Measure(s)</B></P> <P>Frequencies of genotypes for several SNPs in <I>INSR</I> gene that were found as specifically expressed SNPs in a Korean population.</P> <P><B>Result(s)</B></P> <P>Among nine SNPs analyzed in a large population, the genotypic frequencies of eight SNPs were similar, and they had no statistically significant association with PCOS. However, the frequency of a minor allele for one novel SNP, +176477 C>T, was higher in the control group than the patient group.</P> <P><B>Conclusion(s)</B></P> <P>Among the analyzed SNPs, +176477 C>T, a novel SNP in the <I>INSR</I> gene, was associated with the pathogenesis of PCOS in a Korean population.</P>

Association of IL-15 Polymorphisms with Bone Mineral Density in Postmenopausal Korean Women

Koh, Jung-Min,Oh, Bermseok,Ha, Mi-Hyun,Cho, Kyu-Woan,Lee, Jong-Young,Park, Byung Lae,Shin, Hyoung Doo,Bae, Myung-Ae,Kim, Hyun-Ju,Hong, Jung Min,Kim, Tae-Ho,Shin, Hong-In,Lee, Seung Hun,Kim, Ghi Su,Kim Springer-Verlag 2009 Calcified tissue international Vol.85 No.5

Association of FLT3 Polymorphisms With Low BMD and Risk of Osteoporotic Fracture in Postmenopausal Women

Koh, Jung-Min,Oh, Bermseok,Lee, Jong-Young,Lee, Jong-Keuk,Kimm, Kuchan,Park, Byung Lae,Shin, Hyoung Doo,Lee, Il-Kwon,Kim, Hyeoung-Joon,Hong, Jung-Min,Kim, Tae-Ho,Kim, Ghi Su,Kim, Shin-Yoon,Park, Eui K Wiley (John WileySons) 2007 Journal of bone and mineral research Vol.22 No.11

<P>The genetic effects of FLT3 polymorphisms on BMD and fracture risk in postmenopausal women were studied. We found that FLT3+13348C>T polymorphism and haplotype 2 were significantly associated with low BMD and high risk of fracture. Introduction: FMS-related tyrosine kinase 3 (FLT3) has been shown to play a critical role in the development of myelolymphoid progenitors and in the development of osteoclasts, but any possible genetic effect of FLT3 on bone metabolism has not been studied. Materials and Methods: To study a possible genetic effect of FLT3, we directly sequenced the FLT3 gene in 24 Korean individuals and identified 23 sequence variants. Seven polymorphisms were selected and genotyped in Korean postmenopausal women (n = 946). Results: We found that FLT3+13348C>T was associated with low BMD at the lumbar spine (p = 0.04) and femoral neck (p = 0.04). Haplotype analysis revealed that FLT3-ht2 (TTCTT) containing the rare allele in the +13348 position also showed significant association with low BMD in the lumbar spine (p = 0.04) and femoral neck (p = 0.05). Consistent with these results, the FLT3+13348C>T polymorphism and FLT3-ht2 were also significantly associated with high risk of fracture in the vertebrae (OR = 1.44-1.58; p = 0.03-0.04 and OR = 1.45-1.59; p = 0.02-0.03, respectively) and in any sites (OR = 1.34-1.81; p = 0.02-0.03 and OR = 1.34-1.81; p = 0.02-0.03, respectively). Conclusions: These results suggest that FLT3 polymorphisms play a role in determination of BMD and subsequent fractures in postmenopausal women.</P>

Allelic Frequencies of 20 Visible Phenotype Variants in the Korean Population

Lim, Ji Eun,Oh, Bermseok Korea Genome Organization 2013 Genomics & informatics Vol.11 No.2

The prediction of externally visible characteristics from DNA has been studied for forensic genetics over the last few years. Externally visible characteristics include hair, skin, and eye color, height, and facial morphology, which have high heritability. Recent studies using genome-wide association analysis have identified genes and variations that correlate with human visible phenotypes and developed phenotype prediction programs. However, most prediction models were constructed and validated based on genotype and phenotype information on Europeans. Therefore, we need to validate prediction models in diverse ethnic populations. In this study, we selected potentially useful variations for forensic science that are associated with hair and eye color, iris pattern, and facial morphology, based on previous studies, and analyzed their frequencies in 1,920 Koreans. Among 20 single nucleotide polymorphisms (SNPs), 10 SNPs were polymorphic, 6 SNPs were very rare (minor allele frequency < 0.005), and 4 SNPs were monomorphic in the Korean population. Even though the usability of these SNPs should be verified by an association study in Koreans, this study provides 10 potential SNP markers for forensic science for externally visible characteristics in the Korean population.

Implication of Genetic Variants Near <i>TCF7L2</i> , <i>SLC30A8</i> , <i>HHEX</i> , <i>CDKAL1</i> , <i>CDKN2A/B</i> , <i>IGF2BP2</i> , and <i>FTO</i> in Type 2 Diabetes and Obesity in 6,719 Asians

Ng, Maggie C.Y.,Park, Kyong Soo,Oh, Bermseok,Tam, Claudia H.T.,Cho, Young Min,Shin, Hyoung Doo,Lam, Vincent K.L.,Ma, Ronald C.W.,So, Wing Yee,Cho, Yoon Shin,Kim, Hyung-Lae,Lee, Hong Kyu,Chan, Juliana American Diabetes Association 2008 Diabetes Vol.57 No.8

<P><B>OBJECTIVE—</B> Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed <I>TCF7L2</I> as the major type 2 diabetes gene to date in Europeans. However, the implications of these genes in Asians are unclear.</P><P><B>RESEARCH DESIGN AND METHODS—</B> We studied 13 associated single nucleotide polymorphisms from these genes in 3,041 patients with type 2 diabetes and 3,678 control subjects of Asian ancestry from Hong Kong and Korea.</P><P><B>RESULTS—</B> We confirmed the associations of <I>TCF7L2</I>, <I>SLC30A8</I>, <I>HHEX</I>, <I>CDKAL1</I>, <I>CDKN2A</I>/<I>CDKN2B</I>, <I>IGF2BP2</I>, and <I>FTO</I> with risk for type 2 diabetes, with odds ratios ranging from 1.13 to 1.35 (1.3 × 10<SUP>−12</SUP> < <I>P</I><SUB>unadjusted</SUB> < 0.016). In addition, the A allele of rs8050136 at <I>FTO</I> was associated with increased BMI in the control subjects (<I>P</I><SUB>unadjusted</SUB> = 0.008). However, we did not observe significant association of any genetic variants with surrogate measures of insulin secretion or insulin sensitivity indexes in a subset of 2,662 control subjects. Compared with subjects carrying zero, one, or two risk alleles, each additional risk allele was associated with 17% increased risk, and there was an up to 3.3-fold increased risk for type 2 diabetes in those carrying eight or more risk alleles. Despite most of the effect sizes being similar between Asians and Europeans in the meta-analyses, the ethnic differences in risk allele frequencies in most of these genes lead to variable attributable risks in these two populations.</P><P><B>CONCLUSIONS—</B> Our findings support the important but differential contribution of these genetic variants to type 2 diabetes and obesity in Asians compared with Europeans.</P>

Effect of Interaction between Early Menarche and Genetic Polymorphisms on Triglyceride

Lee, Ho-Sun,Leem, Sangseob,Oh, Bermseok,Park, Taesung Hindawi Limited 2019 Oxidative medicine and cellular longevity Vol.2019 No.-

<P>Early menarche has been associated with increased risk of metabolic syndrome. Therefore, investigating the association of each component of metabolic syndrome with age at menarche, and interactions between them, might lead to a better understanding of metabolic syndrome pathogenesis. In this study, we evaluated age at menarche for risk of metabolic syndrome and associations with its components. As a result, the risk of MetS incidence was significantly increased only at ≤12 years of age at menarche (OR = 1.91, <TEX>$ P\symbol{'3C}0.05$</TEX> ). Women with early menarche (≤12 years) had significantly higher levels of triglycerides (<I>β</I> coefficient = 37.83, <TEX>$ P=0.02$</TEX> ). In addition, hypertriglyceridemia was significantly increased at early menarche with 1.99 (95% CI: 1.16-3.41, <TEX>$ P\symbol{'3C}0.01$</TEX> ). With GWAS-based pathway analysis, we found the type 2 diabetes mellitus, stress-activated protein kinase signaling, and Jun amino-terminal kinase cascade pathways (all nominal <TEX>$ P\symbol{'3C}0.001$</TEX> , all FDR < 0.05) to be significantly involved with early menarche on triglyceride levels. These findings may help us understand the role of early menarche on triglyceride and interaction between gene and early menarche on triglyceride for the development of metabolic syndrome.</P>

Allopregnanolone Effects on Transmission in the Brain Stem Solitary Tract Nucleus (NTS)

Kim, Sojin,Kim, Sung-Moon,Oh, Bermseok,Tak, Jihoon,Yang, Eunhee,Jin, Young-Ho Elsevier 2018 NEUROSCIENCE Vol.379 No.-

<P><B>Abstract</B></P> <P>During pregnancy, the progesterone metabolite, allopregnanolone (ALLO), becomes elevated and has been associated with altered levels within the CNS and resulting changes in GABA<SUB>A</SUB> receptor function. Pregnant animals poorly compensate reflexes for a decrease in blood pressure during hemorrhage. Previous works suggested that ALLO decreases baroreflex responses by central actions, however, the underlying mechanisms are poorly understood. In this study, we tested ALLO actions on visceral afferent synaptic transmission at second-order neurons within medial portions of the nucleus tractus solitarius (NTS) using hindbrain slices from non-pregnant female rats. Solitary tract (ST) stimulation-evoked excitatory postsynaptic currents (ST-eEPSCs) in NTS neurons directly connected to vagal afferents within the ST. ST-eEPSCs were functionally identified as monosynaptic by the latency characteristics (low jitter = standard deviation of latency, ≤200 μs) to ST stimulation. Such second-order neurons all displayed spontaneous inhibitory postsynaptic currents (sIPSCs), and low micromolar concentrations of ALLO increased frequency and decay time. At submicromolar concentrations, ALLO induced a tonic, GABAergic inhibitory current and suppressed ST-eEPSCs’ amplitude. While GABA<SUB>A</SUB> receptor antagonist, bicuculline, blocked all ALLO effects, gabazine only blocked sIPSC actions. In current-clamp mode, ALLO perfusion increased failure of ST stimulation to trigger action potentials in most neurons. Thus, our results indicate that ALLO acts to suppress visceral afferent ST synaptic transmission at first synapses by activating pharmacologically distinct GABA<SUB>A</SUB> subtypes at different concentration ranges. This ALLO-mediated attenuated visceral afferent signal integration in NTS may underlie reflex changes in blood pressure during gestation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Allopregnanolone (ALLO) effects on visceral afferent synaptic transmission were tested in female rat hindbrain slices. </LI> <LI> Micromolar concentrations of ALLO increased frequency and decay time of spontaneous inhibitory postsynaptic currents. </LI> <LI> Submicromolar concentrations of ALLO induced extrasynaptic GABAergic inhibitory tonic current. </LI> <LI> ALLO suppressed solitary tract stimulation-evoked excitatory postsynaptic current amplitude in the low nanomolar range. </LI> <LI> ALLO administration increased failure of solitary tract stimulation to trigger action potentials in most neurons. </LI> </UL> </P>