In this study, we propose a novel, intuitive method of constructing an expression quantitative trait (eQT) network that is related to the metabolic syndrome using LOD scores and peak loci for selected eQTs, based on the concept of gene-gene interactions. We selected 49 eQTs that were related to insulin resistance. A variance component linkage analysis was performed to explore the expression loci of each of the eQTs. The linkage peak loci were investigated, and the "support zone" was defined within boundaries of an LOD score of 0.5 from the peak. If one gene was located within the "support zone" of the peak loci for the eQT of another gene, the relationship was considered as a potential "directed causal pathway" from the former to the latter gene. SNP markers under the linkage peaks or within the support zone were searched for in the database to identify the genes at the loci. Two groups of gene networks were formed separately around the genes IRS2 and UGCGL2. The findings indicated evidence of networks between genes that were related to the metabolic syndrome. The use of linkage analysis enabled the construction of directed causal networks. This methodology showed that characterizing and locating eQTs can provide an effective means of constructing a genetic network.
Gene Regulatory Networks ; Insulin Resistance ; Lod Score

High-density lipoprotein (HDL) whose primary role is to transport cholesterol from peripheral tissues to the liver, is associated with the incidence of coronary heart disease. We analyzed HDL cholesterol levels in a genetically isolated population of extended Mongolian families. A total of 1002 individuals (54.5% women) from 95 families were enrolled. After genotyping by use of 1000 microsatellite markers, we performed a genome-wide linkage search with variance component analysis. The estimated heritability of HDL cholesterol was 0.45, revealing that HDL cholesterol was under significant genetic influence. We found peak evidence of linkage (LOD score=1.88) for HDL cholesterol level on chromosome 6(nearest marker D6S1660) and potential evidences for linkage on chromosomes 1, 12 and 19 with the LOD scores of 1.32, 1.44 and 1.14, respectively. These results should pave the way for the discovery of the relevant genes by fine mapping and association analysis.
Cholesterol ; Cholesterol, HDL ; Coronary Disease ; Humans ; Incidence ; Lipoproteins ; Liver ; Lod Score ; Microsatellite Repeats ; Mongolia ; Plasma

High-density lipoprotein (HDL) whose primary role is to transport cholesterol from peripheral tissues to the liver, is associated with the incidence of coronary heart disease. We analyzed HDL cholesterol levels in a genetically isolated population of extended Mongolian families. A total of 1002 individuals (54.5% women) from 95 families were enrolled. After genotyping by use of 1000 microsatellite markers, we performed a genome-wide linkage search with variance component analysis. The estimated heritability of HDL cholesterol was 0.45, revealing that HDL cholesterol was under significant genetic influence. We found peak evidence of linkage (LOD score=1.88) for HDL cholesterol level on chromosome 6(nearest marker D6S1660) and potential evidences for linkage on chromosomes 1, 12 and 19 with the LOD scores of 1.32, 1.44 and 1.14, respectively. These results should pave the way for the discovery of the relevant genes by fine mapping and association analysis.
Cholesterol ; Cholesterol, HDL ; Coronary Disease ; Humans ; Incidence ; Lipoproteins ; Liver ; Lod Score ; Microsatellite Repeats ; Mongolia ; Plasma

BACKGROUNDHereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative disorders with the shared characteristics of slowly progressive spasticity and weakness of the lower limbs. Thirteen loci for autosomal dominant HSP have been mapped.

METHODSA Chinese family with HSP was found in the Shandong province and Inner Mongolia Autonomous Region of China and genomic DNA of all 19 family members was isolated. After exclusion of known autosomal dominant loci, a genome wide scan and linkage analysis were performed.

RESULTSThe known autosomal dominant loci of SPG3A, SPG4, SPG6, SPG8, SPG9, SPG10, SPG12, SPG13, SPG17, SPG19, SPG29, SPG31 and SPG33 were excluded by linkage analysis. The results of a genome wide scan demonstrated candidate linkage to a locus on chromosome 11p14.1-p11.2, over an 18.88 cM interval between markers D11S1324 and D11S1933. A maximal, two point LOD score of 2.36 for marker D11S935 at a recombination fraction (theta) of 0 and a multipoint LOD score of 2.36 for markers D11S1776, D11S1751, D11S1392, D11S4203, D11S935, D11S4083, and D11S4148 at theta=0, suggest linkage to this locus.

CONCLUSIONThe HSP neuropathy in this family may represent a novel genetic entity, which will facilitate discovery of this causative gene.

Adult ; Chromosome Mapping ; Chromosomes, Human, Pair 11 ; Female ; Humans ; Lod Score ; Male ; Spastic Paraplegia, Hereditary ; genetics

OBJECTIVEThe present study performed linkage analysis and gene mapping to find the possible chromosome locus harboring in one family with benign familial infantile convulsions (BFIC) and investigate the possible molecular pathogenesis of BFIC.

METHODSA four-generation family with BFIC was investigated. The family was genotyped using eight hypervariable microsatellite markers covering four loci: D19S245 and D19S250 for the 19q12-13.1 region, D16S3131 and D16S3133 for the 16p12-q12 region, D2S156 and D2S286 for the 2q24 region, and D20S480 and D20S481 for the 20q13.3 region. Polymorphism fragments were amplified using polymerase chain reaction (PCR) method. PCR products for the markers were subjected to electrophoresis on 8% denatured polyacrylamide gel and silver staining for length judgment of amplification fragment. Linkage analysis was performed by use of MLINK in the LINKAGE computer package. Two-point LOD scores were calculated to estimate the linkage relationship.

RESULTSThe two-point LOD scores were less than -2.0 for the genetic markers at chromosomes 19q12-13.1, 16p12-q12 and 2q24 at the recombination rate between 0.000 and 0.01. The two-point LOD scores for D20S481 at the 20q13.3 region were 0.3 and 0.25 at the recombination rate of 0.000 and 0.01, respectively.

CONCLUSIONSThere is no evidence that this family with BFIC is linked to one of the following loci: 19q12-13.1, 16p12-q12 and 2q24, but a possible linkage with 20q13.3 region cannot be excluded.

Chromosome Mapping ; Epilepsy, Benign Neonatal ; genetics ; Female ; Genetic Linkage ; Humans ; Lod Score ; Male ; Microsatellite Repeats

OBJECTIVETo explore the molecular genetic relationship between chromosome 1 and quantitative trait loci for familial schizophrenia.

METHODSA series of assessment scales included positive and negative syndrome scale (PANSS), global assessment of functional scale (GAFS), premorbid schizoid and schizotypal traits scale (PSST), premorbid social adjustment scale (PSA) were applied to quantify the phenotypes of schizophrenia. Non-parametric linkage analysis of quantitative traits was conducted in 32 multiplex pedigrees with schizophrenia by using 29 microsatellite makers on chromosome 1.

RESULTSHaseman-Elston quantitative trait analysis detected a maximum Traditional H-E Lods of 1.73 and a maximum EH H-E Lods of 1.65 of negative symptoms (PANSS-N ) at 147.64 cM, which was overlapped to the positive region of 1q21-23 in qualitative linkage analysis.

CONCLUSIONThe results suggest there might be an independent quantitative trait locus of negative symptoms on 1q21-23 for familial schizophrenia.

Chromosomes, Human, Pair 1 ; genetics ; Family Health ; Genetic Linkage ; Humans ; Lod Score ; Microsatellite Repeats ; Quantitative Trait, Heritable ; Schizophrenia ; genetics

BACKGROUNDHypertension is a complex biological trait that influenced by multiple factors. The encouraging results for hypertension research showed that the linkage analysis can be used to replicate other studies and discover new genetic risk factors. Previous studies linked human chromosome 14 to essential hypertension or blood pressure traits. With a Chinese population, we tried to replicate these findings.

METHODSA linkage scan was performed on chromosome 14 with 14-microsatellite markers with a density of about 10 centi Morgen (cM) in 147 Chinese hypertensive nuclear families. Multipoint non-parametric linkage analysis and exclusion mapping were performed with the GENEHUNTER software, whereas quantitative analysis was performed with the variance component method integrated in the SOLAR package.

RESULTSIn the qualitative analysis, the highest non-parametric linkage score is 1.0 (P = 0.14) at D14S261 in the single point analysis, and no loci achieved non-parametric linkage score more than 1.0 in the multipoint analysis. Maximum-likelihood mapping showed no significant results, either. Subsequently the traditional exclusion criteria of the log-of-the-odds score-2 were adopted, and the chromosome 14 with lambda s > or = 2.4 was excluded. In the quantitative analysis of blood pressure with the SOLAR software, two-point analysis and multipoint analysis suggested no evidence for linkage occurred on chromosome 14 for systolic and diastolic blood pressure.

CONCLUSIONThere was no substantial evidence to support the linkage of chromosome 14 and essential hypertension or blood pressure trait in Chinese hypertensive subjects in this study.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Chromosomes, Human, Pair 14 ; Genetic Linkage ; Humans ; Hypertension ; genetics ; Lod Score ; Middle Aged

In standard interval mapping (IM) of quantitative trait loci (QTL), the QTL effect is described by a normal mixture model. When this assumption of normality is violated, the most commonly adopted strategy is to use the previous model after data transformation. However, an appropriate transformation may not exist or may be difficult to find. Also this approach can raise interpretation issues. An interesting alternative is to consider a skew-normal mixture model in standard IM, and the resulting method is here denoted as skew-normal IM. This flexible model that includes the usual symmetric normal distribution as a special case is important, allowing continuous variation from normality to non-normality. In this paper we briefly introduce the main peculiarities of the skew-normal distribution. The maximum likelihood estimates of parameters of the skew-normal distribution are obtained by the expectation-maximization (EM) algorithm. The proposed model is illustrated with real data from an intercross experiment that shows a significant departure from the normality assumption. The performance of the skew-normal IM is assessed via stochastic simulation. The results indicate that the skew-normal IM has higher power for QTL detection and better precision of QTL location as compared to standard IM and nonparametric IM.
Animals ; Chromosome Mapping ; methods ; Lod Score ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Normal Distribution ; Quantitative Trait Loci ; genetics

Wilson disease gene (WND) locus is presumed to be located in chromosome 13q. There are studies on the clinical heterogeneities and variations between ethnic groups in Europe, North America, and the Middle East and it requires the study of another ethnic group, especially Asian population for the confirmation. This study was an anlysis of restriction fragment length polymorphism of the Wilson's disease with the probes on D13S26, D13S31, and D13S59, The subject was 34 persons of seven families. The serum ceruloplasmin and the serum copper were also measured. The results were as follows: 1) The Wilson disease gene was also presumed to be located in chromosome 13q area in Korean patients and D13S25, D13S26, D13S31 and D13S59 gene loci were also linked to Wilson disease of Koreans. The lod score of D13S25 was 1.45 (theta =0: D13S59, 1.13 (theta =0): D13S26, 247 (theta =0). 2) Three siblings of Wilson disease patients were diagnosed as carriers by the analysis of restriction fragment length polymorphism. 3) In Wilson disease patients, the serum ceruloplasmin and copper was 6.8+/1.8dl, and 64.7+/-38.6microg/dl respectively and it is 18.8+/-6.1 mg/dl and 65.3+/-10.6microg/dl respectively in heterozygotes.
Asian Continental Ancestry Group ; Ceruloplasmin ; Copper ; Ethnic Groups ; Europe ; Genetic Linkage* ; Hepatolenticular Degeneration* ; Heterozygote ; Humans ; Lod Score ; Middle East ; North America ; Polymorphism, Restriction Fragment Length ; Siblings

Anthropometric traits for eyes and nose are complex quantitative traits influenced by genetic and environmental factors. To date, there have been few reports on the contribution of genetic influence to these traits in Asian populations. The aim of this study was to determine the genetic effect and quantitative trait locus (QTL) of seven traits eyes- and nose-related anthropometric measurements in an isolated Mongolian population. Frontal and lateral photographs were obtained from 1,014 individuals (434 males and 580 females) of Mongolian origin. A total of 349 short tandem repeat markers on 22 autosomes were genotyped for each individual. Heritability estimates of the seven ocular and nasal traits, adjusted for significant covariates, ranged from 0.48 to 0.90, providing evidence for a genetic influence. Variance-component linkage analyses revealed 10 suggestive linkage signals on 5q34 (LOD = 3.2), 18q12.2 (LOD = 2.7), 5q15 (LOD = 2.0), 9q34.2 (LOD = 1.9), 5q34 (LOD = 1.9), 17q22 (LOD = 1.9), 13q33.3 (LOD = 2.7), 1q36.22 (LOD = 1.9), 4q32.1 (LOD = 2.1) and 15q22.31 (LOD = 2.9). Our study provides the first evidence that genetics influences nasal and ocular traits in a Mongolian population. Additional collaborative efforts will further extend our understanding of the link between genetic factors and human anthropometric traits.
Anthropometry ; *Asian Continental Ancestry Group ; Eye ; Facial Bones/*anatomy & histology ; Female ; *Genetic Linkage ; *Genome, Human ; Humans ; Lod Score ; Male ; Mongolia ; Nose ; Quantitative Trait Loci