• Journal of Genetic Medicine
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• v.11 no.1
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• pp.11-15
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• 2014

Congenital central hypoventilation syndrome (CCHS) is a disorder of the autonomic nervous system characterized by a decreased response to hypercarbia. CCHS is frequently associated with congenital megacolon; the combination is called Haddad syndrome. CCHS is associated with dysfunction in respiratory features of the autonomic nervous system and with other disorders, including facial deformities, cardiovascular symptoms, and tumors. Patients with CCHS frequently have a mutation in the homeobox protein 2b (PHOX2B) gene. Most mutations involve heterozygous expansion of alanine repeats (GCN). Interestingly, a higher polyalanine repeat number is associated with a more severe clinical phenotype. To clarify the role of PHOX2B in disease pathogenesis, we introduce and review the clinical and molecular features of CCHS and Haddad syndrome.

• Journal of Genetic Medicine
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• v.10 no.1
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• pp.52-56
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• 2013

Mosaic trisomy 14 syndrome is a well-known but unusual chromosomal abnormality with a distinct and recognizable phenotype. Array comparative genomic hybridization (CGH) analysis has recently become a widely used method for detecting DNA copy number changes, in place of traditional karyotype analysis. However, the array CGH shows a limitation for detecting the low-level mosaicism. Here, we report the detailed clinical and cytogenetic findings of patient with low-frequency mosaic trisomy 14, initially considered normal based on usual cut-off levels of array CGH, but confirmed by G-banding karyotyping. Our patient had global developmental delay, short stature, congenital heart disease, craniofacial dysmorphic features, and dark skin patches over her whole body. Estimated mosaicism proportion was 23.3% by G-banding karyotyping and 18.0% by array CGH.

• Journal of Genetic Medicine
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• v.18 no.2
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• pp.75-82
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• 2021

Speech and language functions are highly cognitive and human-specific features. The underlying causes of normal speech and language function are believed to reside in the human brain. Developmental persistent stuttering, a speech and language disorder, has been regarded as the most challenging disorder in determining genetic causes because of the high percentage of spontaneous recovery in stutters. This mysterious characteristic hinders speech pathologists from discriminating recovered stutters from completely normal individuals. Over the last several decades, several genetic approaches have been used to identify the genetic causes of stuttering, and remarkable progress has been made in genome-wide linkage analysis followed by gene sequencing. So far, four genes, namely GNPTAB, GNPTG, NAGPA, and AP4E1, are known to cause stuttering. Furthermore, thegeneration of mouse models of stuttering and morphometry analysis has created new ways for researchers to identify brain regions that participate in human speech function and to understand the neuropathology of stuttering. In this review, we aimed to investigate previous progress, challenges, and future perspectives in understanding the genetics and neuropathology underlying persistent developmental stuttering.

• Reproductive and Developmental Biology
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• v.37 no.4
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• pp.205-211
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• 2013

The swine is one of the most widespread mammalian throughout the whole world. Presently, many studies concerning microsatellites in swine, especially domestic pigs, have been carried out in order to investigate general diversity patterns among either populations or breeds. Until now, a lot of time and effort spend into a single PCR method. But simple and more rapid multiplex PCR methods have been developed. The purpose of this study is to develop a robust set of microsatellites markers (MS marker) for traceability and individual identification. Using multiplex-PCR method with 23 MS marker divided 2 set, various alleles occurring to 5 swine breed (Berkshire, Landrace, Yorkshire, Duroc and Korea native pig) used markers to determine allele frequency and heterozygosity. MS marker found 4 alleles at SW403, S0227, SWR414, SW1041 and SW1377. The most were found 10 alleles at SW1920. Heterozygosity represented the lowest value of 0.102 at SWR414 and highest value of 0.861 at SW1920. So, it was recognized appropriate allele frequency for individual identification in swine. Using multiplex-PCR method, MS markers used to determine individual identification biomarker and breed-specific marker for faster, more accurate and lower analysis cost. Based on this result, a scientific basis was established to the existing pedigree data by applying genetics additionally. Swine traceability is expected to be very useful system and be conducted nationwide in future.

• Journal of Genetic Medicine
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• v.18 no.1
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• pp.31-37
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• 2021

Purpose: To summarize the results of chromosomal microarray analysis (CMA) for copy number variants (CNVs) detection and clinical utility in a single tertiary hospital. Materials and Methods: We performed CMA in 46 patients over the course of two years. Detected CNVs were classified into five categories according to the American College of Medical Genetics and Genomics guidelines and correlated with clinical manifestations. Results: A total of 31 CNVs were detected in 19 patients, with a median CNV number per patient of two CNVs. Among these, 16 CNVs were classified as pathogenic (n=3) or likely pathogenic (LP) (n=11) or variant of uncertain significance (n=4). The 16p11.2 deletion and 16p13.11 deletion classified as LP were most often detected in 6.5% (3/46), retrospectively. CMA diagnostic yield was 24.3% (9/37 patients) for symptomatic patients. The CNVs results of the commercial newborn screening test using next generation sequencing platforms showed high concordance with CMA results. Conclusion: CMA seems useful as a first-tier test for developmental delay with or without congenital anomalies. However, the classification and interpretation of CMA still remained a challenge. Further research is needed for evidence-based interpretation.

• Journal of Genetic Medicine
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• v.12 no.1
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• pp.49-56
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• 2015

We herein report an analysis of a female baby with a de novo dup(10p)/del(10q) chromosomal aberration. A prenatal cytogenetic analysis was performed owing to abnormal ultrasound findings including a choroid plexus cyst, prominent cisterna magna, and a slightly medially displaced stomach. The fetal karyotype showed additional material attached to the terminal region of chromosome 10q. Parental karyotypes were both normal. At birth, the baby showed hypotonia, upslanting palpebral fissures, a nodular back mass, respiratory distress, neonatal jaundice and a suspicious polycystic kidney. We ascertained that the karyotype of the baby was 46,XX,der(10)($pter{\rightarrow}q26.3::p11.2{\rightarrow}pter$) by cytogenetic and molecular cytogenetic analyses including high resolution GTG-and RBG-banding, fluorescence in situ hybridization, comparative genomic hybridization, and short tandem repeat marker analyses. While almost all reported cases of 10p duplication originated from one of the parents with a pericentric inversion, our case is extraordinarily rare as the de novo dup(10p)/del(10q) presumably originated from a rearrangement at the premeiotic stage of the parental germ cell or from parental germline mosaicism.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.21-26
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• 2020

Purpose: To evaluate the additive value of prenatal chromosomal microarray analysis (CMA) in assessing increased nuchal translucency (NT) (≥3.5 mm) with normal karyotype and the possibility of detecting clinically significant genomic imbalance, based on specific indications. Materials and Methods: Invasive samples from 494 pregnancies with NT ≥3.5 mm, obtained from the Research Center of Fertility & Genetics of Hamchoon Women's Clinic between January 2019 and February 2020, were included in this study and CMA was performed in addition to a standard karyotype. Results: In total, 494 cases were subjected to both karyotype and CMA analyses. Among these, 199 cases of aneuploidy were excluded. CMA was performed on the remaining 295 cases (59.7%), which showed normal (231/295, 78.3%) or non-significant copy number variation (CNV), such as benign CNV or variants of uncertain clinical significance likely benign (53/295, 18.0%). Clinically significant CNVs were detected in 11 cases (11/295, 3.7%). Conclusion: Prenatal CMA resulted in a 3% to 4% higher CNV diagnosis rate in fetuses exhibiting increased NT (≥3.5 mm) without other ultrasound detected anomalies and normal karyotype. Therefore, we suggest using high resolution, non- targeting CMA to provide valuable additional information for prenatal diagnosis. Further, we recommend that a genetics specialist should be consulted to interpret the information appropriately and provide counseling and follow-up services after prenatal CMA.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.10
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• pp.1565-1574
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• 2018

Objective: The aim of the present study was to identify genetic variants based on RNA-seq data, obtained via transcriptome sequencing of muscle tissue of pigs differing in muscle histological structure, and to verify the variants' effect on histological microstructure and production traits in a larger pig population. Methods: RNA-seq data was used to identify the panel of single nucleotide polymorphisms (SNPs) significantly related with percentage and diameter of each fiber type (I, IIA, IIB). Detected polymorphisms were mapped to quantitative trait loci (QTLs) regions. Next, the association study was performed on 944 animals representing five breeds (Landrace, Large White, Pietrain, Duroc, and native Puławska breed) in order to evaluate the relationship of selected SNPs and histological characteristics, meat quality and carcasses traits. Results: Mapping of detected genetic variants to QTL regions showed that chromosome 14 was the most overrepresented with the identification of four QTLs related to percentage of fiber types I and IIA. The association study performed on a 293 longissimus muscle samples confirmed a significant positive effect of transforming acidic coiled-coil-containing protein 2 (TACC2) polymorphisms on fiber diameter, while SNP within forkhead box O1 (FOXO1) locus was associated with decrease of diameter of fiber types IIA and IIB. Moreover, subsequent general linear model analysis showed significant relationship of FOXO1, delta 4-desaturase, sphingolipid 1 (DEGS1), and troponin T2 (TNNT2) genes with loin 'eye' area, FOXO1 with loin weight, as well as FOXO1 and TACC2 with lean meat percentage. Furthermore, the intramuscular fat content was positively associated (p<0.01) with occurrence of polymorphisms within DEGS1, TNNT2 genes and negatively with occurrence of TACC2 polymorphism. Conclusion: This study's results indicate that the SNP calling analysis based on RNA-seq data can be used to search candidate genes and establish the genetic basis of phenotypic traits. The presented results can be used for future studies evaluating the use of selected SNPs as genetic markers related to muscle histological profile and production traits in pig breeding.

• BMB Reports
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• v.43 no.2
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• pp.79-90
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• 2010

Mouse models are crucial for the functional annotation of human genome. Gene modification techniques including gene targeting and gene trap in mouse have provided powerful tools in the form of genetically engineered mice (GEM) for understanding the molecular pathogenesis of human diseases. Several international consortium and programs are under way to deliver mutations in every gene in mouse genome. The information from studying these GEM can be shared through international collaboration. However, there are many limitations in utility because not all human genes are knocked out in mouse and they are not yet phenotypically characterized by standardized ways which is required for sharing and evaluating data from GEM. The recent improvement in mouse genetics has now moved the bottleneck in mouse functional genomics from the production of GEM to the systematic mouse phenotype analysis of GEM. Enhanced, reproducible and comprehensive mouse phenotype analysis has thus emerged as a prerequisite for effectively engaging the phenotyping bottleneck. In this review, current information on systematic mouse phenotype analysis and an issue-oriented perspective will be provided.

• Journal of Genetic Medicine
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• v.14 no.2
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• pp.62-66
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• 2017

Interchromosomal insertion of Y chromosome heterochromatin in an autosome was identified in a fetus and a family. A fetal karyotype was analyzed as 46,XX,dup(7)(?q22q21.1) in a referred amniocentesis at 16 weeks of gestation for advanced maternal age. In the familial karyotype analyses for identification of der(7), the mother, the first daughter and the maternal grandmother showed the same der(7) as the fetus's. CBG-banding was positive at 7q22 region of der(7) that indicated inserted material was originated from heterochromatin. The origin of heterochromatic insertion region in der(7) of the fetus and the mother was found in Yq12 region by fluorescent in situ hybridization with a DYZ1 probe. In the specific analysis of Y chromosomal heterochromatic region of ins(7;Y) of the mother, 15 sequence tagged sites from Yp11.3 region including SRY to Yq11.223 region was not detected. Final karyotypes of the mother, the first daughter and the maternal grandmother were reported as 46,XX,der(7)ins(7;Y)(q21.3;q12q12). All female carriers of ins(7;Y) in the family showed normal phenotype and the mother and the maternal grandmother were fertile. A healthy girl was born at term. We report a rare case of familial interchromosomal insertion of Y chromosome heterochromatin detected only in female family members with normal phenotype that was diagnosed prenatally.