• Journal of Genetic Medicine
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• v.15 no.2
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• pp.64-71
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• 2018

Purpose: Overgrowth syndromes are conditions that involve generalized or localized areas of excess growth. In this study, the clinical, molecular, and genetic characteristics of Korean patients with overgrowth syndrome were analyzed. Materials and Methods: We recruited 13 patients who presented with overgrowth syndrome. All patients fulfilled inclusion criteria of overgrowth syndrome. Analysis of the clinical and molecular investigations of patients with overgrowth syndrome was performed retrospectively. Results: Among the 13 patients with overgrowth syndrome, 9 patients (69.2%) were found to have molecular and genetic causes. Among the seven patients with Sotos syndrome (SS), two had a 5q35microdeletion that was confirmed by fluorescent in situ hybridization. In two patients with SS, intragenic mutations including a novel mutation, c.5993T>A (p.M1998L), were found by Sanger sequencing. One patient had one copy deletion of NDS1 gene which was confirmed by multiplex ligation-dependent probe amplification. Among five patients with Beckwith-Wiedemann syndrome, three had aberrant imprinting control regions; 2 hypermethylation of the differentially methylated region of H19, 1 hypomethylation of the differentially methylated region of Kv. In one patient displaying overlapping clinical features of SS, a de novo heterozygous deletion in the chromosomal region 7q22.1-22.3 was found by single nucleotide polymorphism-based microarray. Conclusion: Considering high detection rate of molecular and genetic abnormalities in this study, rigorous investigations of overgrowth syndrome may be an important tool for the early diagnosis and genetic counseling. A detailed molecular analysis of the rearranged regions may supply the clues for the identification of genes involved in growth regulation.

• Clinical and Experimental Reproductive Medicine
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• v.46 no.3
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• pp.132-139
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• 2019

Objective: Vitamin D-binding protein (VDBP) mediates various biological processes in humans. The goal of this study was to investigate whether VDBP gene polymorphisms could predispose Korean women to endometriosis. Methods: We prospectively enrolled women with endometriosis (n = 16) and healthy controls (n = 16). Total serum 25-hydroxyl vitamin D (25(OH)D) concentrations were measured using an Elecsys vitamin D total kit. Levels of bioavailable and free 25(OH)D were calculated. Concentrations of VDBP were measured using a vitamin D BP Quantikine ELISA kit. DNA was extracted using a DNeasy blood & tissue kit. Two single-nucleotide polymorphisms (SNPs; rs4588 and rs7041) in GC, the gene that codes for VDBP, were analyzed using a TaqMan SNP genotyping assay kit. The functional variant of VDBP was determined based on the results of the two SNPs. Results: Gravidity and parity were significantly lower in the endometriosis patients than in the control group, but serum CA-125 levels and the erythrocyte sedimentation rate were significantly higher. Total serum 25(OH)D levels in the endometriosis patients were significantly lower than in the control group. However, serum bioavailable 25(OH)D, free 25(OH)D, and VDBP levels did not differ significantly between the endometriosis and control groups. The genotypes and allele frequencies of GC were similar in both groups. Conclusion: Korean women with endometriosis had lower total serum 25(OH)D concentrations than controls. Neither serum VDBP concentrations nor polymorphisms in the gene coding for VDBP were associated with endometriosis. Further studies are needed to investigate the pathophysiology and clinical implications of 25(OH)D and VDBP in endometriosis.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.7
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• pp.939-948
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• 2019

Objective: Extension and Agouti loci play a key role for proportions of eumelanin and pheomelanin in determining coat color in several species, including goat. Mongolian goats exhibit diverse types of coat color phenotypes. In this study, investigation of the melanocortin 1 receptor (MC1R) coding region in different coat colors in Mongolian goats was performed to ascertain the presence of the extension allele. Methods: A total of 105 goat samples representing three goat breeds were collected for this study from middle Mongolia. A 938 base pair (bp) long coding region of the MC1R gene was sequenced for three different breeds with different coat colors (Gobi Gurwan Saikhan: complete black, Zalaa Jinstiin Tsagaan: complete white, Mongolian native goat: admixture of different of coat colors). The genotypes of these goats were obtained from analyzing and comparing the sequencing results. Results: A total of seven haplotypes defined by five substitution were identified. The five single nucleotide polymorphisms included two synonymous mutations (c.183C>T and c.489G>A) and three missense (non-synonymous) mutations (c.676A>G, c.748T>G, and c.770T>A). Comparison of genotypes frequencies of two common missense mutions using chi-sqaure ($x^2$) test revealed significant differences between coat color groups (p<0.001). A logistic regression analysis additionally suggested highly significant association between genotypes and variation of black versus white uniform combination. Alternatively, most investigated goats (60.4%) belonged to H2 (TGAGT) haplotype. Conclusion: According to the findings obtained in this study on the investigated coat colors, mutations in MC1R gene may have the crucial role for determining eumelanin and pheomelanin phenotypes. Due to the complication of coat color phenotype, more detailed investigation needed.

• Animal Bioscience
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• v.34 no.8
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• pp.1283-1289
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• 2021

Objective: The progestogen-associated endometrial protein (PAEP) gene encodes the main whey protein in milk, β-lactoglobulin. The aim of the study was to investigate polymorphism in the PAEP gene and its association with milk yield, composition, and quality. Methods: Test-day records for 782 dairy cows were analysed. A total of 10 single nucleotide polymorphisms (SNP) within the PAEP gene were investigated. The following parameters were recorded: milk yield (MY, kg/d), percent milk fat (%), protein (PP, %), dry matter (DMP, %) and lactose (LP, %), urea content (UC, mg/L) as well as natural logarithm for somatic cell count (LnSCC, ln). Effect on genomic estimated breeding values accuracy was evaluated with pedigree and single step model. Results: Results show that only three SNPs were polymorphic, creating 5 composite genotypes: P1 to P5. Differences in MY between composite genotypes were noted in the two tested herds. Cows with P5 composite genotypes were characterised by the highest PP and LnSCC and the lowest LP and UC (p<0.05). P4 was linked to an increased DMP and UC, while P3 to an increase in LP and decrease in PP and LnSCC. Both factors are important markers in herd management and have high influences on the herds economics. For 5 out of 7 traits the accuracy of prediction was improved by including the haplotype as a fixed effect. Conclusion: Presented results may suggest a new way to optimise breeding programmes and demonstrate the impact of using genomic data during that process.

• The Plant Pathology Journal
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• v.37 no.2
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• pp.194-199
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• 2021

Blackleg is a serious disease in Brassica plants, causing moderate to severe yield losses in rapeseed worldwide. Although China has not suffered from this disease yet (more aggressive Leptosphaeria maculans is not present yet), it is crucial to take provisions in breeding for disease resistance to have excellent blackleg-resistant cultivars already in the fields or in the breeding pipeline. The most efficient strategy for controlling this disease is breeding plants with identified resistance genes. We selected 135 rapeseed accessions in Sichuan, including 30 parental materials and 105 hybrids, and we determined their glucosinolate and erucic acid content and confirmed 17 double-low materials. A recently developed single-nucleotide polymorphism (SNP) marker, SNP_208, was used to genotype allelic Rlm1/rlm1 on chromosome A07, and 87 AvrLm1-resistant materials. Combined with the above-mentioned seed quality data, we identified 11 AvrLm1-resistant double-low rapeseed accessions, including nine parental materials and two hybrids. This study lays the foundation of specific R gene-oriented breeding, in the case that the aggressive Leptosphaeria maculans invades and establishes in China in the future and a robust and less labor consuming method to identify resistance in canola germplasm.

• Journal of Genetic Medicine
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• v.18 no.2
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• pp.110-116
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• 2021

Microdeletions of chromosome 22q11.2 are one of the most common microdeletions occurring in humans, and is known to be associated with a wide range of highly variable features. These deletions occur within a cluster of low copy repeats (LCRs) in 22q11.2, referred to as LCR22 A-H. DiGeorge (DGS)/velocardiofacial syndrome is the most prevalent form of a 22q11.2 deletions, caused by mainly proximal deletions between LCR22 A and D. As deletions of distal portion to the DGS deleted regions has been extensively studied, the recurrent distal 22q11.2 microdeletions distinct from DGS has been suggested as several clinical entities according to the various in size and position of the deletions on LCRs. We report a case of long-term follow-up of a female diagnosed with a 22q11.2 distal deletion syndrome, identified a deletion of 1.9 Mb at 22q11.21q11.23 (chr22: 21,798,906-23,653,963) using single nucleotide polymorphism array. This region was categorized as distal deletion type of 22q11.2, involving LCR22 D-F. She was born as a preterm, low birth weight to healthy non-consanguineous Korean parents. She showed developmental delay, growth retardation, dysmorphic facial features, and mild skeletal deformities. The patient underwent a growth hormone administration due to growth impairment without catch-up growth. While a height gain was noted, she had become overweight and was subsequently diagnosed with pre-diabetes. Our case could help broaden the genetic and clinical spectrum of 22q11.2 distal deletions.

• Genomics & Informatics
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• v.20 no.1
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• pp.4.1-4.8
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• 2022

Loss of heterozygosity (LOH) is a genomic aberration. In some cases, LOH can be generated without changing the copy number, which is called copy-neutral LOH (CN-LOH). CN-LOH frequently occurs in various human diseases, including cancer. However, the biological and clinical implications of CN-LOH for human diseases have not been well studied. In this study, we compared the performance of CN-LOH determination using three commonly used tools. For an objective comparison, we analyzed CN-LOH profiles from single-nucleotide polymorphism array data from 10 colon adenocarcinoma patients, which were used as the reference for comparison with the CN-LOHs obtained through whole-exome sequencing (WES) data of the same patients using three different analysis tools (FACETS, Nexus, and Sequenza). The majority of the CN-LOHs identified from the WES data were consistent with the reference data. However, some of the CN-LOHs identified from the WES data were not consistent between the three tools, and the consistency with the reference CN-LOH profile was also different. The Jaccard index of the CN-LOHs using FACETS (0.84 ± 0.29; mean value, 0.73) was significantly higher than that of Nexus (0.55 ± 0.29; mean value, 0.50; p = 0.02) or Sequenza (0 ± 0.41; mean value, 0.34; p = 0.04). FACETS showed the highest area under the curve value. Taken together, of the three CN-LOH analysis tools, FACETS showed the best performance in identifying CN-LOHs from The Cancer Genome Atlas colon adenocarcinoma WES data. Our results will be helpful in exploring the biological or clinical implications of CN-LOH for human diseases.

• Genomics & Informatics
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• v.19 no.4
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• pp.37.1-37.7
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• 2021

Genome-wide association studies (GWASs) facilitated the discovery of countless disease-associated variants. However, GWASs have mostly been conducted in European ancestry samples. Recent studies have reported that these European-based association results may reduce disease prediction accuracy when applied in non-Europeans. Therefore, previously reported variants should be validated in non-European populations to establish reliable scientific evidence for precision medicine. In this study, we validated known associations with type 2 diabetes (T2D) and related metabolic traits in 125,850 samples from a Korean population genotyped by the Korea Biobank Array (KBA). At the end of December 2020, there were 8,823 variants associated with glycemic traits, lipids, liver enzymes, and T2D in the GWAS catalog. Considering the availability of imputed datasets in the KBA genome data, publicly available East Asian T2D summary statistics, and the linkage disequilibrium among the variants (r² < 0.2), 2,900 independent variants were selected for further analysis. Among these, 1,837 variants (63.3%) were statistically significant (p ≤ 0.05). Most of the non-replicated variants (n = 1,063) showed insufficient statistical power and decreased minor allele frequencies compared with the replicated variants. Moreover, most of known variants showed <10% genetic heritability. These results could provide valuable scientific evidence for future study designs, the current power of GWASs, and future applications in precision medicine in the Korean population.

• Genomics & Informatics
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• v.19 no.2
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• pp.19.1-19.9
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• 2021

Plant height is an important component of plant architecture and significantly affects crop breeding practices and yield. We studied DNA variations derived from F5 recombinant inbred lines (RILs) with 96.8% homozygous genotypes. Here, we report DNA variations between the normal and dwarf members of four lines harvested from a single seed parent in an F6 RIL population derived from a cross between Glycine max var. Peking and Glycine soja IT182936. Whole genome sequencing was carried out, and the DNA variations in the whole genome were compared between the normal and dwarf samples. We found a large number of DNA variations in both the dwarf and semi-dwarf lines, with one single nucleotide polymorphism (SNP) per at least 3.68 kb in the dwarf lines and 1 SNP per 11.13 kb of the whole genome. This value is 2.18 times higher than the expected DNA variation in the F6 population. A total of 186 SNPs and 241 SNPs were discovered in the coding regions of the dwarf lines 1282 and 1303, respectively, and we discovered 33 homogeneous nonsynonymous SNPs that occurred at the same loci in each set of dwarf and normal soybean. Of them, five SNPs were in the same positions between lines 1282 and 1303. Our results provide important information for improving our understanding of the genetics of soybean plant height and crop breeding. These polymorphisms could be useful genetic resources for plant breeders, geneticists, and biologists for future molecular biology and breeding projects.

• The Plant Pathology Journal
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• v.38 no.6
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• pp.629-636
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• 2022

Colletotrichum species is known as the major causal pathogen of red pepper anthracnose in Korea and various groups of fungicides are registered for the management of the disease. However, the consistent use of fungicides has resulted in the development of resistance in many red pepper-growing areas of Korea. Effective management of the occurrence of fungicide resistance depends on constant monitoring and early detection. Thus, in this study, various methods such as agar dilution method (ADM), gene sequencing, allele-specific polymerase chain reaction (PCR), and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were applied for the detection of benzimidazole resistance among 24 isolates of Colletotrichum acutatum s. lat. and Colletotrichum gloeosporioides s. lat. The result of the ADM showed that C. gloeosporioides s. lat. was classified into sensitive and resistant isolates to benomyl while C. acutatum s. lat. was insensitive at ≥1 ㎍/ml of benomyl. The sequence analysis of the β-tubulin gene showed the presence of a single nucleotide mutation at the 198th amino acid position of five isolates (16CACY14, 16CAYY19, 15HN5, 15KJ1, and 16CAYY7) of C. gloeosporioides s. lat. Allele-specific PCR and PCR-RFLP were used to detect point mutation at 198th amino acid position and this was done within a day unlike ADM which usually takes more than one week and thus saving time and resources that are essential in the fungicide resistance management in the field. Therefore, the molecular techniques established in this study can warrant early detection of benzimidazole fungicide resistance for the adoption of management strategies that can prevent yield losses among farmers.