• Asian-Australasian Journal of Animal Sciences
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• 제28권7호
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• pp.926-935
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• 2015

The efficiency of genome-wide association analysis (GWAS) depends on power of detection for quantitative trait loci (QTL) and precision for QTL mapping. In this study, three different strategies for GWAS were applied to detect QTL for carcass quality traits in the Korean cattle, Hanwoo; a linkage disequilibrium single locus regression method (LDRM), a combined linkage and linkage disequilibrium analysis (LDLA) and a $BayesC{\pi}$ approach. The phenotypes of 486 steers were collected for weaning weight (WWT), yearling weight (YWT), carcass weight (CWT), backfat thickness (BFT), longissimus dorsi muscle area, and marbling score (Marb). Also the genotype data for the steers and their sires were scored with the Illumina bovine 50K single nucleotide polymorphism (SNP) chips. For the two former GWAS methods, threshold values were set at false discovery rate <0.01 on a chromosome-wide level, while a cut-off threshold value was set in the latter model, such that the top five windows, each of which comprised 10 adjacent SNPs, were chosen with significant variation for the phenotype. Four major additive QTL from these three methods had high concordance found in 64.1 to 64.9Mb for Bos taurus autosome (BTA) 7 for WWT, 24.3 to 25.4Mb for BTA14 for CWT, 0.5 to 1.5Mb for BTA6 for BFT and 26.3 to 33.4Mb for BTA29 for BFT. Several candidate genes (i.e. glutamate receptor, ionotropic, ampa 1 [GRIA1], family with sequence similarity 110, member B [FAM110B], and thymocyte selection-associated high mobility group box [TOX]) may be identified close to these QTL. Our result suggests that the use of different linkage disequilibrium mapping approaches can provide more reliable chromosome regions to further pinpoint DNA makers or causative genes in these regions.

• Genomics & Informatics
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• 제19권4호
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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.

• 생명과학회지
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• 제11권3호
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• pp.279-283
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• 2001

Amyotrophic lateral sclerosis(ALS) is a progressive neurologic disorder resulting from the degeneration of upper and lower motor neurons, and is inherited in 10% of cases. About 20% of familial ALS, clinically indistinguishable from sporadic ALS, is caused by mutations of Cu/Zn superoxide dismutase on chromosome 21q22.21 inherited as an autosomal dominant trait. We now report a new locus in the non-SOD1 dominantly inherited ALS. We screened a large ALS family with 11 affected individuals and one obligate gene carrier with genome-wide ABI polymorphic markers using the ABI 377 automated system. No evidence of linkage was obtained with the autosomal markers. We next screened this family with X chromosome markers as there was no evidence of male-to-male tran-smission of the disease. Linkage was established with several X chromosome markers with a lod score up to 3.8; almost the maximum possible score in this family. Our finding imply that a gene for the dominant expression of a neuronal degeneration is coded on X chromosome and raise the question of the role of X-linked genes that escape inactivation in this pathogenesis. More importantly, our finding that a gene causing ALS is localized on X-chromosome has direct investigational relevance to sporadic ALS, where epidemiological studies show male gender predominance(1.3:1) and earlier onset in men by 5-10 years.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.13-13
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• 2017

By the progress of genome sequencing, infrastructures for marker-assisted breeding (MAB) of rice came to be established. Fine mapping and gene isolation have been conducted using the breeding materials derived from natural variations and artificial mutants. Such genetic analysis by the genome-wide dense markers provided us the knowledge about the many genes controlling important traits. We identified several genes or quantitative trait loci (QTL) for heading date, blast resistance, eating quality, high-temperature stress tolerance, and so on. NILs of each gene controlling heading date contribute to elongate the rice harvest period. Determination of precise gene location of blast resistance gene pi21, allowed us to overcome linkage drag, co-introduction of undesirable eating quality. We could also breed the first practical rice cultivar in Japan with a brown planthopper resistance gene bph11 in the genetic back-ground of an elite cultivar. Discovery of major and minor QTLs for good eating quality allowed us to fine-tune of eating quality according to the rice planting area or usage of rice grain. Many rice cultivars have bred efficiently by MAB for several traits, or by marker-assisted backcross breeding through chromosome segment substitution lines (CSSLs) using genetically diverse accessions. We are also systematically supporting the crop breeding of other sectors by MAB or by providing resources such as CSSLs. It is possible to pyramid many genes for important traits by using MAB, but is still difficult to improve the yielding ability. We are performing a Genomic Selection (GS) for improvement of rice biomass and grain yield. We are also trying to apply the genome editing technology for high yield rice breeding.

• Journal of Genetic Medicine
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• 제18권2호
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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.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.141-141
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• 2017

The ubiquitin-proteasome pathway is the major regulatory mechanism in a number of cellular processes for selective degradation of proteins and involves three steps: (1) ATP dependent activation of ubiquitin by E1 enzyme, (2) transfer of activated ubiquitin to E2 and (3) transfer of ubiquitin to the protein to be degraded by E3 complex. F-box proteins are subunit of SCF complex and involved in specificity for a target substrate to be degraded. F-box proteins regulate many important biological processes such as embryogenesis, floral development, plant growth and development, biotic and abiotic stress, hormonal responses and senescence. However, little is known about the F-box genes in wheat. The draft genome sequence of wheat (IWGSC Reference Sequence v1.0 assembly) used to analysis a genome-wide survey of the F-box gene family in wheat. The Hidden Markov Model (HMM) profiles of F-box (PF00646), F-box-like (PF12937), F-box-like 2 (PF13013), FBA (PF04300), FBA_1 (PF07734), FBA_2 (PF07735), FBA_3 (PF08268) and FBD (PF08387) domains were downloaded from Pfam database were searched against IWGSC Reference Sequence v1.0 assembly. RNA-seq paired-end libraries from different stages of wheat, such as stages of seedling, tillering, booting, day after flowering (DAF) 1, DAF 10, DAF 20, and DAF 30 were conducted and sequenced by Illumina HiSeq2000 for expression analysis of F-box protein genes. Basic analysis including Hisat, HTseq, DEseq, gene ontology analysis and KEGG mapping were conducted for differentially expressed gene analysis and their annotation mappings of DEGs from various stages. About 950 F-box domain proteins identified by Pfam were mapped to wheat reference genome sequence by blastX (e-value < 0.05). Among them, more than 140 putative F-box protein genes were selected by fold changes cut-offs of > 2, significance p-value < 0.01, and FDR<0.01. Expression profiling of selected F-box protein genes were shown by heatmap analysis, and average linkage and squared Euclidean distance of putative 144 F-box protein genes by expression patterns were calculated for clustering analysis. This work may provide valuable and basic information for further investigation of protein degradation mechanism by ubiquitin proteasome system using F-box proteins during wheat development stages.

• Genomics & Informatics
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• 제12권3호
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• pp.114-120
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• 2014

Bone mineral density (BMD) is one of the quantitative traits that are genetically inherited and affected by various factors. Over the past years, genome-wide association studies (GWASs) have searched for many genetic loci that influence BMD. A recent meta-analysis of 17 GWASs for BMD of the femoral neck and lumbar spine is the largest GWAS for BMD to date and offers 64 single-nucleotide polymorphisms (SNPs) in 56 associated loci. We investigated these BMD loci in a Korean population called Korea Association REsource (KARE) to identify their validity in an independent study. The KARE population contains genotypes from 8,842 individuals, and their BMD levels were measured at the distal radius (BMD-RT) and midshaft tibia (BMD-TT). Thirteen genomic loci among 56 loci were significantly associated with BMD variations, and 3 loci were involved in known biological pathways related to BMD. In order to find putative functional variants, nearby SNPs in relation to linkage equilibrium were annotated, and their possible functional effects were predicted. These findings reveal that tens of variants, not a single factor, may contribute to the genetic architecture of BMD; have an important role regardless of ethnic group; and may highlight the importance of a replication study in GWASs to validate genuine loci for BMD variation.

• Journal of Animal Science and Technology
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• 제64권5호
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• pp.830-841
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• 2022

Genetic analysis has great potential as a tool to differentiate between different species and breeds of livestock. In this study, the optimal combinations of single nucleotide polymorphism (SNP) markers for discriminating the Yeonsan Ogye chicken (Gallus gallus domesticus) breed were identified using high-density 600K SNP array data. In 3,904 individuals from 198 chicken breeds, SNP markers specific to the target population were discovered through a case-control genome-wide association study (GWAS) and filtered out based on the linkage disequilibrium blocks. Significant SNP markers were selected by feature selection applying two machine learning algorithms: Random Forest (RF) and AdaBoost (AB). Using a machine learning approach, the 38 (RF) and 43 (AB) optimal SNP marker combinations for the Yeonsan Ogye chicken population demonstrated 100% accuracy. Hence, the GWAS and machine learning models used in this study can be efficiently utilized to identify the optimal combination of markers for discriminating target populations using multiple SNP markers.

• Journal of Plant Biotechnology
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• 제43권3호
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• pp.261-271
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• 2016

세계적인 과수작물로서의 경제적 중요성에도 불구하고, 감귤 생산은 주로 자연교잡 실생이나 눈 돌연변이로부터의 선발 또는 단순 품종 도입 등을 통해 이루어지고 있는 실정이다. 긴 유년기, 다배성, 자가불화합성과 같은 감귤 고유의 식물학적 특성, 주요 형질들(병저항성, 수량성, 품질 등)의 QTL에 의한 조절 등은 전통 육종을 통한 우수 품종의 개발을 어렵게 하는 요인이다. 지구 온난화에 의한 생산 여건의 급격한 변화, 소비자 요구 다양화 등은 고품질 감귤의 조기 선발과 안정적 생산, 품종 다양화, 육종 비용 절감 등을 위한 체계적인 감귤 분자육종 프로그램의 도입을 요구하고 있다. 동위효소를 이용한 최초의 감귤 연관지도 작성이 이루어진 이래, 다양한 분자표지를 이용한 연관지도 작성, 생물(CTV, CiLV, ABS, 선충] 및 비생물적(염분, 저온) 스트레스, 아포믹시스, 다배성, 과실착색(카로티노이드, 안토시아닌), 무종자, 웅성불임, 신맛 적음, 생식, 형태(나무, 잎, 꽃, 열매 등), 과실 품질, 종자수, 수량성, 조기 착과 등과 연관된 분자표지 발굴, QTL 맵핑 등이 이루어졌다. CTV 저항성과 적육(안토시아닌 축적) 형질에 대해서는 유전자 클로닝이 이루어졌고, 교배 육종 효율 증대 및 비용 절감을 위해 교잡배와 주심배를 구분하기 위한 다수의 simple sequence repeat (SSR) 분자표지가 개발되었다. 최근, 스위트오렌지와 '클레멘타인' 만다린에 대한 고품질의 표준 유전체가 완성되어 유전체 기반 감귤 분자육종을 위한 토대가 마련되었다. 표준 유전체 정보를 토대로 대규모 분자표지(SNP, SSR, InDel) 기반의 표준 연관 및 물리지도 작성, 비교 유전체 지도 작성, gene annotation, 전사체 분석 등이 활발히 이루어지고 있다. 감귤 유전자원 및 핵심집단에 대해 표준 유전체 기반 비교 유전체 분석, GBS (genotyping-by-sequencing), GWAS (genome wide association study) 등을 통해 감귤의 다양한 형질과 연관된 분자마커 발굴 및 개발, 유용/변이 유전자 클로닝 등에 관한 연구가 가속화될 것으로 전망된다. 또한 표적 유전체 교정 및 VIGS (virus-induced gene silencing) 기술도 유전자 마커의 검증을 비롯한 감귤 분자육종 프로그램에 활발히 이용될 것이다.

• Asian-Australasian Journal of Animal Sciences
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• 제32권3호
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• pp.341-349
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• 2019

Objective: Internal organs indirectly affect economic performance and well-being of animals. Study of internal organs during later layer period will allow full utilization of layer hens. Hence, we conducted a genome-wide association study (GWAS) to identify potential quantitative trait loci or genes that potentially contribute to internal organ weight. Methods: A total of 1,512 chickens originating from White Leghorn and Dongxiang Blue-Shelled chickens were genotyped using high-density Affymetrix 600 K single nucleotide polymorphism (SNP) array. We conducted a GWAS, linkage disequilibrium analysis, and heritability estimated based on SNP information by using GEMMA, Haploview and GCTA software. Results: Our results displayed that internal organ weights show moderate to high (0.283 to 0.640) heritability. Variance partitioned across chromosomes and chromosome lengths had a linear relationship for liver weight and gizzard weight ($R^2=0.493$, 0.753). A total of 23 highly significant SNPs that associated with all internal organ weights were mainly located on Gallus gallus autosome (GGA) 1 and GGA4. Six SNPs on GGA2 affected heart weight. After the final analysis, five top SNPs were in or near genes 5-Hydroxytryptamine receptor 2A, general transcription factor IIF polypeptide 2, WD repeat and FYVE domain containing 2, non-SMC condensin I complex subunit G, and sonic hedgehog, which were considered as candidate genes having a pervasive role in internal organ weights. Conclusion: Our findings provide an understanding of the underlying genetic architecture of internal organs and are beneficial in the selection of chickens.