• Communications for Statistical Applications and Methods
• /
• v.16 no.3
• /
• pp.397-408
• /
• 2009

The development of microarray technology makes possible to analyse many thousands of genes simultaneously. While it is important to test each gene whether it shows changes in expression associated with a phenotype, human diseases are thought to occur through the interactions of multiple genes within a same functional cafe-gory. Recent research interests aims to directly test the behavior of sets of functionally related genes, instead of focusing on single genes. Gene set enrichment analysis(GSEA), significance analysis of microarray to gene-set analysis(SAM-GS) and parametric analysis of gene set enrichment(PAGE) have been applied widely as a tool for gene-set analyses. We describe their problems and propose an alternative method using a parametric analysis by adopting normal score transformation of gene expression values. Performance of the newly derived method is compared with previous methods on three real microarray datasets.

• Journal of Life Science
• /
• v.19 no.10
• /
• pp.1495-1498
• /
• 2009

Type 2-diabetes is a typical polygenic disease complex, for which several common risk alleles have been identified. Adiponectin, which modulates insulin resistance as well as glucose and lipid metabolism, has recently been associated with type 2-diabetes (T2DM). Therefore, we investigated the genotype for the T45G and G267T polymorphisms in adiponectin genes in the Korean population and compared genotypes of patients with those of a control group. 100 patients (63 male, 37 female), who previously underwent T2DM and 100 controls (36 male, 63 female) participated in this study. There was a strong association between T45G polymorphism in the adiponectin gene and T2DM. The present study shows that adiponectin T45G polymorphism may be associated with the pathogenesis of T2DM. Further studies with a larger population may be needed for the development of diagnostic methods at genetic levels such as DNA chip.

• Journal of Embryo Transfer
• /
• v.22 no.3
• /
• pp.167-172
• /
• 2007

Pituitary-specific transcription factor (PIT1) 유전자는 동물의 성장을 조절하고 근육 형성에 관여하는 유전자로서 최근에는 단일염기다형성 변이가 한우를 비롯한 동물에서 관찰되었으며, 한우의 경제 형질과 연관성이 보고되었다. 본 연구는 PIT1 유전자의 단일염기다형성 변이가 한우에서 성장 인자에 미치는 영향과 경제 형질에 대한 유전자형간 육종가와의 상관성에 대해 알아보고자 하였다. 도체 성적을 보유하고 있는 한우 후보종모우 집단 268두를 대상으로 PIT1 유전자 A1256G 다형성을 조사하여 유전자형의 빈도를 분석하였고 각각의 유전형에 따른 기본적인 검정 성적을 바탕으로 경제 형질과의 연관성을 비교 분석하였다. 268두의 한우에서 PIT1 유전자의 A1256G 유전자형 빈도는 MseI 제한 효소를 사용했을 때 A 유전자 빈도(0.37)보다 G 유전자 빈도(0.62)가 높게 나타났다. 통계적 분석을 통하여 각 유전자형에 대한 경제 형질과의 관련성을 분석한 결과, 각 유전자형 간에 12개월령 체중 (body weight 12, BW12)에서 유의한 차이를 보였고, 등지방 두께 육종가 (Backfat thickness-estimated breeding value, BF-EBV)와도 유의한 차이가 있었지만 (p<0.05), marbling score (MS), carcass weight (CW), M. longissimus dorsi area (LDA) 등 다른 경제 형질과는 통계학적으로 유의한 차이가 없었다. PIT1 유전자의 A1256G 다형성은 한우의 성장과 도체체중에 관여하는 인자로 작용하는 것으로 보여진다.

• Journal of Life Science
• /
• v.20 no.12
• /
• pp.1758-1763
• /
• 2010

Osteoporosis is a complex systemic skeletal disease and a major public health concern worldwide. It is a heritable disorder characterized mainly by low bone density and/or low trauma osteoporotic fractures, both of which have strong genetic determination. However, the specific genetic variants determining risk for low bone density are still largely unknown. Here, we performed association analysis to elucidate the possible relationship between genetic polymorphisms in the SQSTM1 gene and low bone density. By examining a total of 7225 (men: 3622, women: 3603) subjects from the Korean population in the Korean Association REsource (KARE) study, we discovered that SQSTM1 gene polymorphisms were associated with bone density. The results of the BD-RT (bone density estimated by T-score at distal radius) showed that three SNPs (rs513235, rs3734007, and rs11249661) within the SQSTM1 gene were significantly associated with bone density. The results of the BD-TT (bone density estimated by T-score at midshaft tibia) showed that four SNPs (rs513235, rs3734007, rs2241349, and rs11249661) were significantly associated with bone density. The three SNPs (rs513235, rs3734007, and rs11249661) had common significance in both BD-RT and BD-TT. In summary, we found statistically significant SNPs in the SQSTM1 gene that are associated with bone density traits. Therefore, our findings suggest SQSTM1 gene could be related to pathogenesis of osteoporosis.

• Journal of Periodontal and Implant Science
• /
• v.34 no.3
• /
• pp.671-681
• /
• 2004

Genomic Project 이후로 다양한 질환에 있어서 유전적인 영향에 관한 연구가 진행되고 있다. 이 연구의 목적은 한국인 치주질환 환자에서 Fc ${\gamma}R$ 유전자의 유전자다형성과 치주질환 특성과의 관련성을 알아보는 것이다. 치주적으로 건강한 한국인 90명(대조군, 남자64명, 여자26명), 중도 만성 치주염환자 40명(severe chronic periodontitis patients; severe CP, 남자 24명, 여자 16명)을 대상으로 임상지수(치주낭 깊이, 입상부착소실, 치은지수, 치태지수, 탐침 후 출혈지수, 치조골소실)를 측정하였다. 또한 이들의 정맥혈에서 추출한 DNA를 PCR(Polymerase Chain Reaction)법, 전기영동법 등을 이용하여 Fc ${\gamma}RIIIa$ , Fc ${\gamma}RIIIb$의 대립유전자의 존재여부를 확인하였다. 이를 바탕으로 각 유전자의 다형성 및 Fc ${\gamma}R$ 복합유전자형 (Fc ${\gamma}R$ composite genotype)을 확인하여, 각 군 간을 비교하였다. 치주질환의 특성과 유전자 다형성과의 관련성을 알아보기 위하여 Fc ${\gamma}R$ 유전자에 대한 유전자다형성을 조사한 결과 다음과 같은 결과를 얻을 수 있었다. 1. Fc ${\gamma}RIIla$에 대한 유전자다형성 연구결과 대조군과 severe CP, AgP군 사이에서, severe CP와 AgP군 사이에서는 대립유전자분포가 서로 유의성 있는 차이를 나타내었지만(p<0.05), Fc ${\gamma}RIIlb$에서는 유의성 있는 차이를 보이지 않았다(p>0.05). 2. Fc ${\gamma}R$ 복합유전자형간의 비교에서 유의성 있는 차이를 발견할 수 없었다(p>0.05). 이와 같은 결과를 종합하여 볼 때 실험대상 한국인 치주염환자에서 Fc ${\gamma}R$ 유전자에 대한 다형성분석에서 Fc ${\gamma}RIIIa$ 대립유전자가 치주염에 대한 감수성과 관련되어 있다고 생각된다. 이 연구의 결과는 유전자의 차이가 치주질환의 감수성 판단의 자료로 활용할 수 있는 가능성을 보여주고 있다.

• Clinical and Experimental Pediatrics
• /
• v.52 no.4
• /
• pp.476-480
• /
• 2009

Purpose : The purpose of this study was to investigate the polymorphisms of the TNF-alpha promotor gene, its susceptibility to Kawasaki disease (KD) and to assess whether the TNF-alpha promotor gene polymorphism was related the risk of coronary artery lesions (CALs). Methods : From January 2003 to January 2007, 51 children (30 boys and 21 girls) with KD and 48 children forming an age-matched control group were studied. DNA from the peripheral blood of all the children was sampled, and the DNA polymorphisms of the 5' flanking regions of the TNF-alpha promoter gene at position -308 [guanine (G) to adenine (A)] were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Then, the relationship between KD and the TNF-alpha promotor gene polymorphisms was evaluated. Results : The A allele frequency of the -308 site of the TNF-alpha promotor gene was 17.6% (9/51) for children with KD and 6.8% (3/48) for the control group children, but this result was not statistically significant. Twenty-four patients experienced CALs within 60 days after the onset of symptoms. KD children with TNF-alpha -308 A allele had lower frequencies of CALs (12.5% versus 22.2%, P>0.05). Conclusion : The DNA polymorphism of the -308 site TNF-alpha gene was not associated with susceptibility to KD and a risk of CALs. Multicenter, large-scale randomized controlled trials are needed for further study.

• The Korean Journal of Applied Statistics
• /
• v.22 no.4
• /
• pp.781-792
• /
• 2009

At an early stage of genomic investigations, a small sample of microarrays is used in gene expression experiments to identify small subsets of candidate genes for a further accurate investigation. Unlike the statistical analysis methods for a large sample of microarrays, an appropriate statistical method for identifying small subsets is a randomization test that provides exact P values. These exact P values from a randomization test for a small sample of microarrays are discrete. The possible existence of differentially expressed genes in the sample of a full set of genes can be tested for the null hypothesis of a uniform distribution. Subsets of smaller P values are of prime interest for a further accurate investigation and identifying these outlier cells from a multinomial distribution of P values is possible by M test of Fuchs et al. (1980). Above all, the genome-wide gene expressions in microarrays are correlated, but the majority of statistical analysis methods in the microarray analysis are based on an independence assumption of genes and ignore the possibly correlated expression levels. We investigated with simulation studies the effect that correlated gene expression levels could have on the randomization test results and M test results, and found that the effects are often not ignorable.

• Journal of Life Science
• /
• v.20 no.10
• /
• pp.1498-1504
• /
• 2010

A number of studies have shown that the calpain system is important in normal skeletal muscle growth. An increased rate of skeletal muscle growth can result from a decreased rate of muscle protein degradation, and this is associated with a decrease in activity of the calpain system, due principally to a large increase in calpastatin (CAST) activity. The CAST gene, mapped to BTA 7, is considered a candidate gene for beef tenderness and muscle growth. The present study used comparative sequencing of five novel polymorphisms located within exon 20 and 22 of the bovine CAST gene in Hanwoo: exon20- 109737G/A, 109749T/C, 109823T/C, exon22- 116151G/A, intron- 109926G/A. The association of the CAST SNPs with economic traits was studied. The 109926G/A showed a significant effect only on the longissimus muscle area (LMA, p<0.05) in Hanwoo. 109926G/A with the genotype GG had a significantly higher effect on LMA (75.35) than the genotype AA (69.6, p<0.05). Also, the 116151G/A showed a significant effect only on weight at 18 months (W18, p<0.05). 116151G/A with the genotype GG had a significantly higher effect on W18 (428.54) than the genotype AA (408.87, p<0.05).

• Journal of KIISE:Computer Systems and Theory
• /
• v.33 no.3
• /
• pp.157-165
• /
• 2006

The change of external/internal factors of the cell rquires specific biological functions to maintain life. Such functions encourage particular genes to jnteract/regulate each other in multiple ways. Accordingly, we applied a linear decomposition model IFSA, which derives hidden variables, called the 'expression mode' that corresponds to the functions. To interpret gene interaction/regulation, we used a cross-correlation method given an expression mode. Linear decomposition models such as principal component analysis (PCA) and independent component analysis (ICA) were shown to be useful in analyzing high dimensional DNA microarray data, compared to clustering methods. These methods assume that gene expression is controlled by a linear combination of uncorrelated/indepdendent latent variables. However these methods have some difficulty in grouping similar patterns which are slightly time-delayed or asymmetric since only exactly matched Patterns are considered. In order to overcome this, we employ the (IFSA) method of [1] to locate phase- and shut-invariant features. Membership scoring functions play an important role to classify genes since linear decomposition models basically aim at data reduction not but at grouping data. We address a new function essential to the IFSA method. In this paper we stress that IFSA is useful in grouping functionally-related genes in the presence of time-shift and expression phase variance. Ultimately, we propose a new approach to investigate the multiple interaction information of genes.

• Journal of Embryo Transfer
• /
• v.21 no.4
• /
• pp.273-280
• /
• 2006

MC4R, PRKAG3, FABP3, and ESR have reported as important candidate genes related to some economic traits in pigs. To investigate the association between these genes and economic traits, the analysis of restriction fragment length polymorphism (RFLP) was conducted on 147 individuals (96 Durocs and 86 Korea native pigs; KNP) using single nucleotide polymorphism (SNP). Different genotype frequencies of 4 candidate genes were observed in Duroc and KNP. There were significant associations between MC4R polymorphic site and average daily gain (ADG, p<0.05) and backfat thickness (BF, p<0.05) in the Duroc, ADG (p<0.05) and days to 70 kg (p<0.05) in KNP. PRXAG3 polymorphic site were significantly .elated to BF (p<0.05) in the Duroc, ADG (p<0.05) and days to 70 kg (p<0.05) in the KNP. In FABP3, association with BF (p<0.05) in the Duroc, ADG (p<0.05) and days to 70 kg (p<0.05) in the KNP were found. ESR polymorphic site was not significantly associated to any other traits.