Joint Identification of Multiple Genetic Variants of Obesity in a Korean Genome-wide Association Study

오소희,조서애,박태성 한국유전체학회 2010 Genomics & informatics Vol.8 No.3

In recent years, genome-wide association (GWA) studies have successfully led to many discoveries of genetic variants affecting common complex traits, including height, blood pressure, and diabetes. Although GWA studies have made much progress in finding single nucleotide polymorphisms (SNPs) associated with many complex traits, such SNPs have been shown to explain only a very small proportion of the underlying genetic variance of complex traits. This is partly due to that fact that most current GWA studies have relied on single-marker approaches that identify single genetic factors individually and have limitations in considering the joint effects of multiple genetic factors on complex traits. Joint identification of multiple genetic factors would be more powerful and provide a better prediction of complex traits, since it utilizes combined information across variants. Recently, a new statistical method for joint identification of genetic variants for common complex traits via the elastic-net regularization method was proposed. In this study, we applied this joint identification approach to a large-scale GWA dataset (i.e.,8842 samples and 327,872 SNPs) in order to identify genetic variants of obesity for the Korean population. In addition, in order to test for the biological significance of the jointly identified SNPs, gene ontology and pathway enrichment analyses were further conducted.

The Usage of an SNP-SNP Relationship Matrix for Best Linear Unbiased Prediction (BLUP) Analysis Using a Community-Based Cohort Study

이영섭,김희발,김현정,조서애 한국유전체학회 2014 Genomics & informatics Vol.12 No.4

Best linear unbiased prediction (BLUP) has been used to estimate the fixed effects and random effects of complex traits. Traditionally, genomic relationship matrix-based (GRM) and random marker-based BLUP analyses are prevalent to estimatethe genetic values of complex traits. We used three methods: GRM-based prediction (G-BLUP), random marker-basedprediction using an identity matrix (so-called single-nucleotide polymorphism [SNP]-BLUP), and SNP-SNP variance-covariancematrix (so-called SNP-GBLUP). We used 35,675 SNPs and R package “rrBLUP” for the BLUP analysis. The SNP-SNP relationshipmatrix was calculated using the GRM and Sherman-Morrison-Woodbury lemma. The SNP-GBLUP result was very similar toG-BLUP in the prediction of genetic values. However, there were many discrepancies between SNP-BLUP and the other twoBLUPs. SNP-GBLUP has the merit to be able to predict genetic values through SNP effects.

DNA Degradation이 Genotyping-by-Sequencing(GBS) 자료 기반 한우 유전적 표지 발굴에 미치는 영향

유동안,김권도,김덕경,조서애 강원대학교 동물자원공동연구소 2017 동물자원연구 Vol.28 No.4

Genotyping-by-sequencing (GBS) is a cost-efficient method which can be useful for SNP marker discovery in a population of interest. GBS is genome reduction sequencing method using restriction enzyme. The quality of DNA is a key factor which could have an influence in downstream analysis. However, there have not been many studies which investigated the impact of DNA degradation and the quality of the data on marker discovery. In this study, GBS data of 6 Hanwoo samples (H1~6) showing differing level of DNA degradation were compared. Re-sequencing pipeline was followed to investigate the impact of DNA degradation on marker discovery. As a result, we found that the quantity and quality of SNPs were not affected in the sample H5 and H6 with moderately degraded DNA. On the other hand, marker discovery was greatly affected in samples with severe DNA degradation (H3 and H4). The findings in this study support that GBS is a robust genotyping method towards moderate DNA degradation.

Changes in Cell Membrane Fatty Acid Composition of Streptococcus thermophilus in Response to Gradually Increasing Heat Temperature

민봉규,김꽃님,Vladimir Li,조서애,김희발 한국미생물·생명공학회 2020 Journal of microbiology and biotechnology Vol.30 No.5

In this study, a method of heat adaptation was implemented in an attempt to increase the upper thermal threshold of two Streptococcus thermophilus found in South Korea and identified the alterations in membrane fatty acid composition to adaptive response to heat. In order to develop heat tolerant lactic acid bacteria, heat treatment was continuously applied to bacteria by increasing temperature from 60°C until the point that no surviving cell was detected. Our results indicated significant increase in heat tolerance of heat-adapted strains compared to the wild type (WT) strains. In particular, the survival ratio of basically low heat-tolerant strain increased even more. In addition, the strains with improved heat tolerance acquired cross protection, which improved their survival ratio in acid, bile salts and osmotic conditions. A relation between heat tolerance and membrane fatty acid composition was identified. As a result of heat adaptation, the ratio of unsaturated to saturated fatty acids (UFA/SFA) and C18:1 relative concentration were decreased. C6:0 in only heatadapted strains and C22:0 in only the naturally high heat tolerant strain were detected. These results support the hypothesis, that the consequent increase of SFA ratio is a cellular response to environmental stresses such as high temperatures, and it is able to protect the cells from acid, bile salts and osmotic conditions via cross protection. This study demonstrated that the increase in heat tolerance can be utilized as a mean to improve bacterial tolerance against various environmental stresses.

Deciphering signature of selection affecting beef quality traits in Angus cattle

김희발,윤준,Tadelle Dessie,조서애,오성종,이학교,김희발 한국유전학회 2018 Genes & Genomics Vol.40 No.1

Artificial selection towards a desired phenotype/ trait has modified the genomes of livestock dramatically that generated breeds that greatly differ in morphology, production and environmental adaptation traits. Angus cattle are among the famous cattle breeds developed for superior beef quality. This paper aimed at exploring genomic regions under selection in Angus cattle that are associated with meat quality traits and other associated phenotypes. The whole genome of 10 Angus cattle was compared with 11 Hanwoo (A-H) and 9 Jersey (A-J) cattle breeds using a crosspopulation composite likelihood ratio (XP-CLR) statistical method. The top 1% of the empirical distribution was taken as significant and annotated using UMD3.1. As a result, 255 and 210 genes were revealed under selection from A–H and A–J comparisons, respectively. The WebGestalt gene ontology analysis resulted in sixteen (A–H) and five (A–J) significantly enriched KEGG pathways. Several pathways associated with meat quality traits (insulin signaling, type II diabetes mellitus pathway, focal adhesion pathway, and ECM-receptor interaction), and feeding efficiency (olfactory transduction, tight junction, and metabolic pathways) were enriched. Genes affecting beef quality traits (e.g., FABP3, FTO, DGAT2, ACS, ACAA2, CPE, TNNI1), stature and body size (e.g., PLAG1, LYN, CHCHD7, RPS20), fertility and dystocia (e.g., ESR1, RPS20, PPP2R1A, GHRL, PLAG1), feeding efficiency (e.g., PIK3CD, DNAJC28, DNAJC3, GHRL, PLAG1), coat color (e.g., MC1-R) and genetic disorders (e.g., ITGB6, PLAG1) were found to be under positive selection in Angus cattle. The study identified genes and pathways that are related to meat quality traits and other phenotypes of Angus cattle. The findings in this study, after validation using additional or independent dataset, will provide useful information for the study of Angus cattle in particular and beef cattle in general.

Genome-wide Association Study (GWAS) and Its Application for Improving the Genomic Estimated Breeding Values (GEBV) of the Berkshire Pork Quality Traits

이영섭,정현수,Mengistie Taye,김현정,가소정,류연철,조서애 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.11

The missing heritability has been a major problem in the analysis of best linear unbiased prediction (BLUP). We introduced the traditional genome-wide association study (GWAS) into the BLUP to improve the heritability estimation. We analyzed eight pork quality traits of the Berkshire breeds using GWAS and BLUP. GWAS detects the putative quantitative trait loci regions given traits. The single nucleotide polymorphisms (SNPs) were obtained using GWAS results with p value <0.01. BLUP analyzed with significant SNPs was much more accurate than that with total genotyped SNPs in terms of narrow-sense heritability. It implies that genomic estimated breeding values (GEBVs) of pork quality traits can be calculated by BLUP via GWAS. The GWAS model was the linear regression using PLINK and BLUP model was the G-BLUP and SNP-GBLUP. The SNP-GBLUP uses SNP-SNP relationship matrix. The BLUP analysis using preprocessing of GWAS can be one of the possible alternatives of solving the missing heritability problem and it can provide alternative BLUP method which can find more accurate GEBVs.

Prediction of Genes Related to Positive Selection Using Whole-Genome Resequencing in Three Commercial Pig Breeds

김효영,Kelsey Caetano-Anolles,서민석,권영진,조서애,서강석,김희발 한국유전체학회 2015 Genomics & informatics Vol.13 No.4

Selective sweep can cause genetic differentiation across populations, which allows for the identification of possible causative regions/genes underlying important traits. The pig has experienced a long history of allele frequency changes through artificial selection in the domestication process. We obtained an average of 329,482,871 sequence reads for 24 pigs from three pig breeds: Yorkshire (n = 5), Landrace (n = 13), and Duroc (n = 6). An average read depth of 11.7 was obtained using whole-genome resequencing on an Illumina HiSeq2000 platform. In this study, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio tests were implemented to detect genes experiencing positive selection for the genome-wide resequencing data generated from three commercial pig breeds. In our results, 26, 7, and 14 genes from Yorkshire, Landrace, and Duroc, respectively were detected by two kinds of statistical tests. Significant evidence for positive selection was identified on genes ST6GALNAC2 and EPHX1 in Yorkshire, PARK2 in Landrace, and BMP6, SLA-DQA1, and PRKG1 in Duroc.These genes are reportedly relevant to lactation, reproduction, meat quality, and growth traits. To understand how these single nucleotide polymorphisms (SNPs) related positive selection affect protein function, we analyzed the effect of non-synonymous SNPs. Three SNPs (rs324509622, rs80931851, and rs80937718) in the SLA-DQA1 gene were significant in the enrichment tests, indicating strong evidence for positive selection in Duroc. Our analyses identified genes under positive selection for lactation, reproduction, and meat-quality and growth traits in Yorkshire, Landrace, and Duroc, respectively.

- Invited Review - African Indigenous Cattle: Unique Genetic Resources in a Rapidly Changing World

Okeyo Mwai,Olivier Hanotte,권영준,조서애 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.7

At least 150 indigenous African cattle breeds have been named, but the majority of African cattle populations remain largely uncharacterized. As cattle breeds and populations in Africa adapted to various local environmental conditions, they acquired unique features. We know now that the history of African cattle was particularly complex and while several of its episodes remain debated, there is no doubt that African cattle population evolved dramatically over time. Today, we find a mosaic of genetically diverse population from the purest Bos taurus to the nearly pure Bos indicus. African cattle are now found all across the continent, with the exception of the Sahara and the river Congo basin. They are found on the rift valley highlands as well as below sea level in the Afar depression. These unique livestock genetic resources are in danger to disappear rapidly following uncontrolled crossbreeding and breed replacements with exotic breeds. Breeding improvement programs of African indigenous livestock remain too few while paradoxically the demand of livestock products is continually increasing. Many African indigenous breeds are endangered now, and their unique adaptive traits may be lost forever. This paper reviews the unique known characteristics of indigenous African cattle populations while describing the opportunities, the necessity and urgency to understand and utilize these resources to respond to the needs of the people of the continent and to the benefit of African farmers.

Comparative genomic analysis of Lactobacillus plantarum GB-LP4 and identification of evolutionarily divergent genes in high-osmolarity environment

정재훈,김권도,유동안,이찬호,강정선,조경진,강대경,곽우리,윤숙희,손화선,김희발,조서애 한국유전학회 2018 Genes & Genomics Vol.40 No.2

Lactobacillus plantarum is one of the widely-used probiotics and there have been a large number of advanced researches on the effectiveness of this species. However, the difference between previously reported plantarum strains, and the source of genomic variation among the strains were not clearly specified. In order to understand further on the molecular basis of L. plantarum on Korean traditional fermentation, we isolated the L. plantarum GB-LP4 from Korean fermented vegetable and conducted whole genome assembly. With comparative genomics approach, we identified the candidate genes that are expected to have undergone evolutionary acceleration. These genes have been reported to associate with the maintaining homeostasis, which are generally known to overcome instability in external environment including low pH or high osmotic pressure. Here, our results provide an evolutionary relationship between L. plantarum species and elucidate the candidate genes that play a pivotal role in evolutionary acceleration of GB-LP4 in high osmolarity environment. This study may provide guidance for further studies on L. plantarum.