• Journal of Genetic Medicine
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• 제21권1호
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• pp.22-30
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• 2024

Purpose: Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant diseases caused by heterozygous mutation in the NF1 gene. Mutation detection is complex owing to the large size of the NF1 gene, the presence of a high number of partial pseudogenes, and the great variety of mutations. We aimed to study the mutation spectrum of NF1 gene in Korean patients with NF1. Materials and Methods: We have analyzed total 69 unrelated patients who were clinically diagnosed with NF1. PCR and sequencing of the NF1 gene was performed in all unrelated index patients. Additionally, multiplex ligation-dependent probe amplification (MLPA) test of the NF1 and SPRED1 gene analysis (sequencing and MLPA test) were performed in patients with negative results from NF1 gene sequencing analysis. Results: Fifty-five different variants were identified in 60 individuals, including six novel variants. The mutations included 36 single base substitutions (15 missense and 21 nonsense), eight splicing mutations, 13 small insertion or deletions, and three gross deletions. Most pathogenic variants were unique. The mutations were evenly distributed across exon one through 58 of NF1, and no mutational hot spots were found. When fulfilling the National Institutes of Health criterion for the clinical diagnosis of NF1, the detection rate was 84.1%. Cafe-au-lait macules were observed in all patients with NF1 mutations. There is no clear relationship between specific mutations and clinical features. Conclusion: This study revealed a wide spectrum and genetic basis of patients with NF1 in Korea. Our results aim to contribute genetic management and counseling.

• International Journal of Industrial Entomology and Biomaterials
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• 제24권1호
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• pp.41-47
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• 2012

The Scarites aterrimus (Coleoptera: Carabidae) dwells exclusively on coastal sandy dunes. Previously, we investigated the nation-wide magnitude and nature of genetic diversity of the species using mitochondrial COI gene and found moderate to low magnitude of sequence diversity, the presence of closely related haplotypes, and relatively high gene flow estimate. Based on these observations we concluded that the species had no historical barriers that bolster genetic subdivision and possible population decline. In this study, we additionally sequenced mitochondrial COII gene from 23 individuals collected from 9 Korean localities to confirm previous findings. Sequencing of 688 bp COII gene provided 5 haplotypes ranging in sequence divergence from 0.145% to 0.291% (1 ~ 2 bp), further confirming low sequence divergence of the species. Gene flow estimates and genetic diversity estimates also support the previous findings that there had been no historical barriers that bolster genetic subdivision.

• Asian-Australasian Journal of Animal Sciences
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• 제28권9호
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• pp.1235-1243
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• 2015

The goat Capra hircus is one of several economically important livestock in China. Advances in molecular genetics have led to the identification of several single nucleotide variation markers associated with genes affecting economic traits. Validation of single nucleotide variations in a whole-transcriptome sequencing is critical for understanding the information of molecular genetics. In this paper, we aim to develop a large amount of convinced single nucleotide polymorphisms (SNPs) for Cashmere goat through transcriptome sequencing. In this study, the transcriptomes of Cashmere goat skin at four stages were measured using RNA-sequencing and 90% to 92% unique-mapped-reads were obtained from total-mapped-reads. A total of 56,231 putative SNPs distributed among 10,057 genes were identified. The average minor allele frequency of total SNPs was 18%. GO and KEGG pathway analysis were conducted to analyze the genes containing SNPs. Our follow up biological validation revealed that 64% of SNPs were true SNPs. Our results show that RNA-sequencing is a fast and efficient method for identification of a large number of SNPs. This work provides significant genetic resources for further research on Cashmere goats, especially for the high density linkage map construction and genome-wide association studies.

• Journal of Korea Artificial Intelligence Association
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• 제2권1호
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• pp.7-14
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• 2024

In this paper, we explore the application of RNA-sequencing data and ensemble machine learning to predict lung cancer and treatment strategies for lung cancer, a leading cause of cancer mortality worldwide. The research utilizes Random Forest, XGBoost, and LightGBM models to analyze gene expression profiles from extensive datasets, aiming to enhance predictive accuracy for lung cancer prognosis. The methodology focuses on preprocessing RNA-seq data to standardize expression levels across samples and applying ensemble algorithms to maximize prediction stability and reduce model overfitting. Key findings indicate that ensemble models, especially XGBoost, substantially outperform traditional predictive models. Significant genetic markers such as ADGRF5 is identified as crucial for predicting lung cancer outcomes. In conclusion, ensemble learning using RNA-seq data proves highly effective in predicting lung cancer, suggesting a potential shift towards more precise and personalized treatment approaches. The results advocate for further integration of molecular and clinical data to refine diagnostic models and improve clinical outcomes, underscoring the critical role of advanced molecular diagnostics in enhancing patient survival rates and quality of life. This study lays the groundwork for future research in the application of RNA-sequencing data and ensemble machine learning techniques in clinical settings.

• Journal of Plant Biotechnology
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• 제43권3호
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• pp.272-280
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• 2016

국화는 관상용, 약용으로 활용되는 주요한 화훼 작물중의 하나이다. 국화의 육종 프로그램은 다양한 품종의 개발에 기여하였으나, 다른 주요한 식량, 채소작물에서 보여졌듯이 전통적인 표현형 기반의 품종선발에서 분자표지를 활용한 선발로 진일보할 필요가 있다. 이러한 분자육종은 유전학, 분자생물학, 최근에는 유전체 연구로 규명된 형질연관 분자표지에 의존한다. 그러나 자가불화합성, 자식약세, 이질육배체, 이형접합성, 거대한 유전체와 같은 국화의 생식적, 유전적, 유전체의 특성으로 인하여 이러한 연구는 심각하게 지연되고 있다. 그럼에도 불구하고 유전연구를 통하여 국화의 유전자지도가 구축되었고 꽃, 잎, 식물구조와 같은 국화의 주요한 형질과 연관된 분자표지가 규명되었다. 염기서열 분석기술이 발달됨에 따라 국화의 전사체가 해독되어 국화의 표준유전자 목록이 구축되고 발달단계에 따라 혹은 생물적 비생물적 환경에서 특이적으로 발현되는 유전자도 규명되었다. 또한 2배체인 야생의 국화속 식물의 유전체 해독 프로젝트가 시작되었다. 이러한 대량의 염기서열 정보는 국화의 분자육종을 위한 근원적인 자원으로 활용될 수 있을 것이다. 이 총설에서는 국화의 분자유전학, 유전체 연구의 현황을 요약하고 향후 전망을 논의한다.

• Radiation Oncology Journal
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• 제33권2호
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• pp.149-154
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• 2015

Purpose: We performed exome sequencing in a breast cancer family without BRCA mutations. Materials and Methods: A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members. Results: We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined. Conclusion: Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies.

• Asian-Australasian Journal of Animal Sciences
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• 제31권1호
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• pp.13-18
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• 2018

Objective: Meat quality including muscle color in chickens is an important trait and continuous selective pressures for fast growth and high yield have negatively impacted this trait. This study was conducted to investigate genetic variations responsible for regulating muscle color. Methods: Whole genome re-sequencing analysis using Illumina HiSeq paired end read method was performed with pooled DNA samples isolated from two broiler chicken lines divergently selected for muscle color (high muscle color [HMC] and low muscle color [LMC]) along with their random bred control line (RAN). Sequencing read data was aligned to the chicken reference genome sequence for Red Jungle Fowl (Galgal4) using reference based genome alignment with NGen program of the Lasergene software package. The potential causal single nucleotide polymorphisms (SNPs) showing non-synonymous changes in coding DNA sequence regions were chosen in each line. Bioinformatic analyses to interpret functions of genes retaining SNPs were performed using the ingenuity pathways analysis (IPA). Results: Millions of SNPs were identified and totally 2,884 SNPs (1,307 for HMC and 1,577 for LMC) showing >75% SNP rates could induce non-synonymous mutations in amino acid sequences. Of those, SNPs showing over 10 read depths yielded 15 more reliable SNPs including 1 for HMC and 14 for LMC. The IPA analyses suggested that meat color in chickens appeared to be associated with chromosomal DNA stability, the functions of ubiquitylation (UBC) and quality and quantity of various subtypes of collagens. Conclusion: In this study, various potential genetic markers showing amino acid changes were identified in differential meat color lines, that can be used for further animal selection strategy.

• 생명과학회지
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• 제14권4호
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• pp.627-635
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• 2004

주문진 근해의 동해산 넙치, 통영과 거제의 양식산 넙치, 그리고 북한 해역의 동해산 넙치를 이용하여 넙치 ND-4와 cytochrome b유전자의 다양성을 관찰하기 위하여 DGES와 DNA 염기서열 검색을 병행하였는데, 각각의 다른 지역에서 얻은 넙치들은 ND-4-2와 ND-4-3 영역에서 특징적인 DNA 다양성이 있었으나 넙치의 cytochrome b유전자에서는 지역간의 차이를 보이는 유전자 변이가 발견되지 않았다. 따라서 본 연구에서 넙치의 지역별 차이를 구별하는 원산지 판별에는 사용된 DGES와 DNA 염기서열 검색 방법이 효과적이었으며, 넙치의 유전자에서는 개체간의 변이가 ND-4-2와 ND-4-3 영역에서 구별되는 유전자 다양성이 관찰되었으므로, 넙치의 원산지 판정을 위한 유전자 검사에는 ND-4-2와 ND-4-3영역의 검색이 필요하다.

• Genes and Genomics
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• 제40권12호
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• pp.1279-1285
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• 2018

Interdigitating dendritic cell sarcoma (IDCS) is an aggressive neoplasm and is an extremely rare disease, with a challenging diagnosis. Etiology of IDCS is also unknown and most studies with only case reports. In our case, immunohistochemistry showed that the tumor cells were positive for S100, CD45, and CD68, but negative for CD1a and CD21. This study aimed to investigate the causative factors of IDCS by sequencing the protein-coding regions of IDCS. We performed whole-exome sequencing with genomic DNA from blood and sarcoma tissue of the IDCS patient using the Illumina Hiseq 2500 platform. After that, we conducted Sanger sequencing for validation of sarcoma-specific variants and gene ontology analysis using DAVID bioinformatics resources. Through comparing sequencing data of sarcoma with normal blood, we obtained 15 nonsynonymous single nucleotide polymorphisms (SNPs) as sarcoma-specific variants. Although the 15 SNPs were not validated by Sanger sequencing due to tumor heterogeneity and low sensitivity of Sanger sequencing, we examined the function of the genes in which each SNP is located. Based on previous studies and gene ontology database, we found that POLQ encoding DNA polymerase theta enzyme and FNIP1 encoding tumor suppressor folliculin-interacting protein might have contributed to the IDCS. Our study provides potential causative genetic factors of IDCS and plays a role in advancing the understanding of IDCS pathogenesis.

• Journal of Genetic Medicine
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• 제20권2호
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• pp.39-45
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• 2023

As advanced sequencing technologies continue to uncover an increasing number of variants in genes associated with human genetic diseases, there is a growing demand for systematic approaches to assess the impact of these variants on human development, health, and disease. While in silico analyses have provided valuable insights, it is essential to complement these findings with model organism studies to determine the functional consequences of genetic variants in vivo. Drosophila melanogaster is an excellent genetic model for such functional studies due to its efficient genetic technologies, high gene conservation with humans, accessibility to mutant fly resources, short life cycles, and cost-effectiveness. The traditional GAL4-UAS system, allowing precise control of gene expression through binary regulation, is frequently employed to assess the effects of monoallelic variants. Recombinase medicated cassette exchange or CRISPR-Cas9-mediated GAL4 insertion within coding introns or substitution of gene body with Kozak-Gal4 result in the loss-of-function of the target gene. This GAL4 insertion strategy also enables the expression of reference complementary DNA (cDNA) or cDNA carrying genetic variants under the control of endogenous regulatory cis elements. Furthermore, the CRISPR-Cas9-directed tissue-specific knockout and cDNA rescue system provides the flexibility to investigate candidate variants in a tissue-specific and/or developmental-timing dependent manner. In this review, we will delve into the diverse genetic techniques available in Drosophila and their applications in diagnosing and studying numerous undiagnosed diseases over the past decade.