SUMMARY: HapAnalyzer is an analysis system that provides minimum analysis methods for the SNP-based association studies. It consists of Hardy-Weinberg equilibrium (HWE) test, linkage disequilibrium (LD) computation, haplotype reconstruction, and SNP (or haplotype)-phenotype association assessment. It is well suited to a case-control association study for the unrelated population.
Case-Control Studies ; Haplotypes* ; Linkage Disequilibrium

An alternative way of constructing ancestral graphs, which is different from the coalescent-based approach, is proposed using population linkage disequilibrium (LD) data. The main difference from the existing method is the construction of the ancestral graphs based on variants instead of individual sequences. Therefore, the key of the proposed method is to use the order of allele ages in the graphs. Distinct from the previous age-estimation methods, allele ages are estimated from full haplotype information by examining the number of generations from the initial complete LD to the current decayed state for each two variants depending on the direction of LD decay between variants. Using a simple algorithmic procedure, an ancestral graph can be derived from the expected allele ages and current LD decay status. This method is different in many ways from previous methods, and, with further improvement, it might be a good replacement for the current approaches.
Alleles ; Family Characteristics ; Haplotypes ; Linkage Disequilibrium ; Recombination, Genetic

OBJECTIVE: Categorical syndromes such as schizophrenia may represent complexes of many continuous psychological structural phenotypes along several dimensions of personality development/degeneration. The present study investigated the heritability and familiality of personality dimensions in Korean families with schizophrenic linkage disequilibrium (LD). METHODS: We recruited 179 probands (with schizophrenia) as well as, whenever possible, their parents and siblings. We used the Temperament and Character Inventory (TCI) to measure personality and symptomatic dimensions. The heritability of personality dimensions in a total of 472 family members was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). To measure familiality, we compared the personality dimensions of family members with those of 336 healthy unrelated controls using analysis of variance (ANOVA) analysis. RESULTS: Three of the seven TCI variables were significantly heritable and were included in subsequent analyses. The three groups (control, unaffected first-degree relative, case) were found to significantly differ from one another, with the expected order of average group scores, for all heritable dimensions. CONCLUSION: Despite several study limitations with respect to family recruitment and phenotyping, our results show that aberrations in several personality dimensions related to genetic-environment coactions or interactions may underlie the complexity of the schizophrenic syndrome.
Humans ; Linkage Disequilibrium* ; Parents ; Phenotype ; Schizophrenia ; Siblings ; Temperament*

Quantitative trait loci (QTL) and their additive, dominance and epistatic effects play a critical role in complex trait variation. It is often infeasible to detect multiple interacting QTL due to main effects often being confounded by interaction effects. Positioning interacting QTL within a small region is even more difficult. We present a variance component approach nested in an empirical Bayesian method, which simultaneously takes into account additive, dominance and epistatic effects due to multiple interacting QTL. The covariance structure used in the variance component approach is based on combined linkage disequilibrium and linkage (LDL) information. In a simulation study where there are complex epistatic interactions between QTL, it is possible to simultaneously fine map interacting QTL using the proposed approach. The present method combined with LDL information can efficiently detect QTL and their dominance and epistatic effects, making it possible to simultaneously fine map main and epistatic QTL.
Chromosome Mapping ; Epistasis, Genetic ; Genetic Linkage ; Humans ; Linkage Disequilibrium ; Monte Carlo Method ; Quantitative Trait Loci ; genetics

PURPOSE: Single-nucleotide polymorphism (SNP) markers within LIN28B have been reported to be related to the timing of pubertal growth. However, no study has investigated the frequency of genetic markers in girls with precocious puberty (PP) or early puberty (EP). This study aimed to determine the frequency of putative genetic markers in girls with PP or EP. METHODS: Genomic DNAs were obtained from 77 and 109 girls that fulfilled the criteria for PP and EP, respectively. The controls in this study were 144 healthy volunteers between 20 and 30 years of age. The haplotypes were reconstructed using 11 SNPs of LIN28B, and haplotype association analysis was performed. The haplotype frequencies were compared. Differences in the clinical and laboratory parameters were analyzed according to the haplotype dosage. RESULTS: Eleven SNPs in LIN28B were all located in a block that was in linkage disequilibrium. The haplotype could be reconstructed using 2 representative SNPs, rs4946651 and rs369065. The AC haplotype was less frequently observed in the PP group than in the controls (0.069 vs. 0.144, P=0.010). The trend that girls with non-AC haplotypes tended to have earlier puberty onset (P=0.037) was illustrated even in the EP+PP patient group by Kaplan-Meier analysis. CONCLUSION: The results of the present study showed that non-AC haplotypes of LIN28B had a significant association with PP in girls.
DNA ; Genetic Markers ; Haplotypes ; Humans ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide ; Puberty ; Puberty, Precocious

The antigen (phenotype), gene (allele) and haplotype frequencies of HLA class I were analysed in 4,622 Koreans. With allele frequencies of over 0.05, the most frequent HLA-A,-B and -C antigens were A2, A24, A33, A11, A26, A31; B62, B51, B44, B54, B61, B35, B58, B60; Cw3, Cw1, Cw4, Cw7. Of these A2, A24, Cw1 and Cw3 were present in very high frequencies, respectively (0.3211, 0.2200, 0.2204, and 0.3737). The most common haplotypes with frequencies larger than 0.02 were A2-Blank, A33-B44, A33-B58, A11-B62, A24-B51, A24-B54, A2-B27, B54-Cw1, B58-Cw3, B51-Blank, B61-Cw3, B62-Cw4, B35-Cw3, B44-Blank, B60-Cw3, B27-Cw1, A2-Cw3, A2-Cw1, A24-Cw1, A33-Cw3, A26-Cw3, and A11-Cw4. A significant negative linkage disequilibrium was found for the haplotypes of A2-B7, A2-B44, A2-B58, A24-B13, A24-B27, A33-B54 and A33-B62, of which frequencies were larger than 0.003. The B-C and A-C haplotypes which showed the significant negative linkage disequilibrium were B44-Cw1, B51-Cw1, B44-Cw3,B62-Blank, A2-Cw4, A2-Blank, A11-Cw3, A11-Blank and A33-Cw1 and had frequencies higher than 0.01. The findings presented here could be used per se to estimate the populational relationships or as the control data for HLA-disease investigation. Furthermore they could provide the scope for the definition of new antigens.
*Alleles ; Gene Frequency ; *Genes, MHC Class I ; *Haplotypes ; Humans ; Korea ; Linkage Disequilibrium

Most common diseases are caused by multiple genetic and environmental factors. Among the genetic factors, single nucleotide polymorphisms (SNPs) are common DNA sequence variations in individuals and can serve as important genetic markers. Recently, investigations of gene-based and whole genome-based SNPs have been applied to association studies for marker discovery. However, SNPs are so population-specific that the association needs to be verified. Fifty-five genes and 384 SNPs were selected based on association with disease. Genotypes of 337 SNPs in candidate genes were determined using Illumina Sentrix Array Matrix (SAM) chips by an allelespecific extension method in 364 unrelated Korean individuals. Allelic frequencies of SNPs were compared with those of other populations obtained from the International HapMap database. Minor allele frequencies, linkage disequilibrium blocks, tagSNPs, and haplotypes of functional candidate SNPs in 55 genetic disease-associated genes were provided. Our data may provide useful information for the selection of genetic markers for genebased genetic disease-association studies of the Korean population.
Base Sequence ; Gene Frequency ; Genetic Markers ; Genotype ; Haplotypes ; HapMap Project ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide*

Next-generation sequencing (NGS) technology has become a trend in the genomics research area. There are many software programs and automated pipelines to analyze NGS data, which can ease the pain for traditional scientists who are not familiar with computer programming. However, downstream analyses, such as finding differentially expressed genes or visualizing linkage disequilibrium maps and genome-wide association study (GWAS) data, still remain a challenge. Here, we introduce a dockerized web application written in R using the Shiny platform to visualize pre-analyzed RNA sequencing and GWAS data. In addition, we have integrated a genome browser based on the JBrowse platform and an automated intermediate parsing process required for custom track construction, so that users can easily build and navigate their personal genome tracks with in-house datasets. This application will help scientists perform series of downstream analyses and obtain a more integrative understanding about various types of genomic data by interactively visualizing them with customizable options.
Dataset ; Genome ; Genome-Wide Association Study ; Genomics ; Humans ; Linkage Disequilibrium ; Sequence Analysis, RNA

Antigen processing (TAP, HLA-DM and LMP) genes map within the major histocompatibility complex (MHC) class II region between the HLA-DQB1 and -DPB1 loci, and are involved in the processing of peptides bound to HLA class I or class II molecules. In order to determine the allele frequencies of antigen processing genes and the various linkage disequilibria existing among these genes, we have analyzed TAP1, TAP2, HLA-DMA, and HLA-DMB, LMP2, LMP7 polymorphisms in 184 unrelated healthy Koreans using the rnethod of PCR-SSCP, ARMS-PCR and PCR-RFLP. The frequencies of antigen processing genes were TAP1A (77.7%), TAP1*B (17.1%), TAP1*C (5.2%), TAP2*A (41.6%), TAP2*B (31.3%), TAP2*C (3.3%), TAP2*D (0.8%), TAP2*E (6.5%), TAP2*G (0.8%), HLA-DMA*0101 (81.5%), HLA-DMA*0102 (18.2%), HLA-DMA*0103 (0.3%), HLA-DMB*0101 (42.9%), HLA-DMB*0102 (19.0%), HLA-DMB*0103 (38.0%), LMP2*R (78.8%), LMP2*H (21.2%), LMP7*A (35.3%), LMP7*B (56.0%), LMP7*C (4.9%), and LMP7*D (3.8%). We also analysed two- locus association among each locus. Many significant positive associations were observed between these two loci, such as between HLA-DMB and TAP1, between HLA-DMA and HLA-DMB, between LMP2 and LMP7, and between TAP1 and LMP7. Conversely, any significant linkage disequilibrium was not detected between HLA-DMB and LMP2. These results could be used as control data for disease association and population genetics studies in Korean population.
Antigen Presentation* ; Gene Frequency ; Genetics, Population ; Linkage Disequilibrium ; Major Histocompatibility Complex ; Peptides

Genome-wide association (GWA) studies have found many important genetic variants that affect various traits. Since these studies are useful to investigate untyped but causal variants using linkage disequilibrium (LD), it would be useful to explore the haplotypes of single-nucleotide polymorphisms (SNPs) within the same LD block of significant associations based on high-density variants from population references. Here, we tried to make a haplotype catalog affecting body mass index (BMI) through an integrative analysis of previously published whole-genome next-generation sequencing (NGS) data of 7 representative Korean individuals and previously known Korean GWA signals. We selected 435 SNPs that were significantly associated with BMI from the GWA analysis and searched 53 LD ranges nearby those SNPs. With the NGS data, the haplotypes were phased within the LDs. A total of 44 possible haplotype blocks for Korean BMI were cataloged. Although the current result constitutes little data, this study provides new insights that may help to identify important haplotypes for traits and low variants nearby significant SNPs. Furthermore, we can build a more comprehensive catalog as a larger dataset becomes available.
Body Mass Index* ; Dataset ; Genome-Wide Association Study ; Haplotypes* ; Korea ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide