OBJECTIVETo identify the candidate chromosomal region for congenital preauricular fistula (CPF) through analysis of an affected Chinese family.

METHODSConventional linkage analysis using short tandem repeats (STR) markers was performed to investigate three chromosomal regions 8q11.1-q13.3, 1q32-q34.3 and 14q31.1-q31.3.

RESULTSNone of 16 STRs could attain a LOD score of more than -2.0 (theta=0). Therefore, the three regions were all excluded as the candidate region for the disease.

CONCLUSIONCPF features high genetic heterogeneity. The family may have a causative gene elsewhere. Whole-genome-based study is needed to identify its genetic etiology.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 14 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Craniofacial Abnormalities ; genetics ; Female ; Humans ; Lod Score ; Male ; Microsatellite Repeats ; Pedigree

OBJECTIVETo perform genome-wide linkage analysis for an ethnic Han Chinese pedigree with schizophrenia in order to locate the susceptibility genes.

METHODSGenomic DNA was extracted from 4 mL of peripheral blood using conventional phenol-chloroform method. Illumina Infinium Linkage 24 BeadChips chip was used for determining the genotypes through detection of single nucleotide polymorphisms (SNPs). After processing the raw data using Illumina BeadStudio software, two-point nonparametric linkage analysis and two-point parametric linkage analysis were performed with Merlin software.

RESULTSBy two-point nonparametric linkage analysis, 27 sites with high LOD scores (LOD=0.63-0.75, P U+003C 0.05) were identified. Among these, 3 SNPs(rs993694, rs992690 rs1861577) were located in 12p12.3 region, whilst the remainders were located in 4p12-q22 region. Two-point parametric linkage analysis under a dominant model has yielded almost identical results.

CONCLUSIONChromosomal regions 4p12-q22 and 12p12.3 probably contain susceptibility genes for schizophrenia.

Asian Continental Ancestry Group ; genetics ; China ; Chromosomes, Human, Pair 12 ; Chromosomes, Human, Pair 4 ; Female ; Genetic Linkage ; Genome-Wide Association Study ; Genotype ; Humans ; Lod Score ; Male ; Pedigree ; Polymorphism, Single Nucleotide ; Schizophrenia ; genetics

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

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

OBJECTIVESTo identify the loci involved in nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Northern Chinese people in Shenyang by using genomewide and interaction linkage scan.

METHODSTwo multiplex families in Shenyang from North China were ascertained through probands with NSCL/P. Blood of every member was drawn for DNA extraction and analysis. Genotypes were available for 382 autosomal short tandem repeat (STR) markers from the ABI Prism Linkage Mapping Set version 2.5. Linkage between markers and NSCL/P was assessed by 2-point parametric LOD scores, multipoint-heterogeneity parametric LOD scores (HLODs), and multipoint nonparametric linkage score (NPL).

RESULTSThe initial scan suggested linkage on Chromosomes 1, 2, and 15. In subsequent fine mapping, 1q32-q42 showed a maximum multipoint LOD score of 1.9(empirical P=0.013) and an NPL score of 2.35 (empirical P=0.053). For 2p24-p25, the multipoint NPL increased to 2.94 (empirical P=0.007). 2-locus interaction analysis obtained a maximum NPL score of 3.73 (P=0.00078) and a maximum LOD score of 3 for Chromosome 1 (at 221 cM) and Chromosome 2 (at 29 cM).

CONCLUSIONBoth parametric and nonparametric linkage scores greatly increased over the initial linkage scores on 1q32-q42, suggesting a susceptibility locus in this region. Nonparametric linkage gave a strong evidence for a candidate region on chromosome 2p24-p25. The superiority of 2-locus linkage scores compared to single-locus scores gave additional evidence for linkage on 1q32-q42 and 2p24-p25, and suggested that certain genes in the two regions may contribute to NCSL/P risks with interaction.

China ; Chromosome Mapping ; Chromosomes, Human ; genetics ; Cleft Lip ; complications ; genetics ; Cleft Palate ; complications ; genetics ; Genetic Linkage ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lod Score ; Microsatellite Repeats ; genetics ; Pedigree

OBJECTIVETo identify the disease-causing gene in a four-generation Chinese family with 9 members affected with primary congenital lymphoedema (PCL, also known as Milroy disease).

METHODSLinkage analysis was performed with a few microsatellite markers flanking the candidate genetic loci for PCL, including 3 known genes associated with autosomal dominant PCL. For mutation analysis, VEGFR3 gene was sequenced with DNA from the proband. Direct DNA sequencing of exon 25 of the VEGFR3 gene was performed in all family members.

RESULTSThe disease gene in the family was mapped to chromosome 5q35.3 with a maximum Lod score of 2.07. Direct DNA sequencing of VEGFR3 gene revealed a heterozygous C to T transition at nucleotide 3341, resulting in p.Pro1114Leu mutation. The p.Pro1114Leu mutation co-segregated with all affected individuals in the family.

CONCLUSIONThis study identified a C3341T (p.Pro1114Leu) mutation in the VEGFR3 gene in a Chinese family with PCL, provided evidence that VEGFR3 mutation can cause PCL in Chinese.

Amino Acid Substitution ; Asian Continental Ancestry Group ; genetics ; Cataract ; genetics ; Genetic Loci ; Humans ; Lod Score ; Lymphedema ; genetics ; Microsatellite Repeats ; genetics ; Mutation ; Point Mutation ; Vascular Endothelial Growth Factor Receptor-3 ; genetics

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

Although the genetic basis for bone mineral density (BMD) has been studied by many groups so far, genes responsible for this complex trait has not been completely revealed. In order to localize quantitative trait loci (QTLs) for BMD variation in Asian population, the study was designed using a group of Mongolian population, a genetically closed population with a homogeneous lifestyle. BMD was measured at the left and right wrists and ankles using DEXA in 1,082 participants from 142 families. Genotyping of 13 polymorphic microsatellitemarkers on chromosome 13 (average spacing 8-9 cM) and two-point and multipoint linkage analysis wereperformed. In two-point linkage analysis, we identified two markers, D13S175 (6.03 cM) and D13S265 (68.73cM) that had LOD scores greater than 1 for left ankle (LOD=2.09, LOD=1.49, respectively). We also found a marker D13S175 (6.03 cM) with a high LOD for left wrist (LOD=1.49) and the markers D13S265 (68.73 cM) and D13S217 (17.21 cM) for the right wrist (LOD= 1.82, LOD= 1.62, respectively). Among these significant marker regions, only two regions at 17 cM (13p11) and 65 cM (13q21) for the right wrist overlapped with major QTLs reported in following multipoint linkage analysis (LOD= 1.7549, LOD=1.4462, respectively). This study provides the possible evidence of the presence of QTLs affecting right wrist BMD in Mongolian populations on 13p11 and 13q21. Modest evidence was also found for genes affecting left ankle and left wrist BMD on 13p13.
Animals ; Ankle ; Asian Continental Ancestry Group ; Bone Density ; Chromosomes, Human, Pair 13 ; Humans ; Life Style ; Lod Score ; Morphinans ; Quantitative Trait Loci ; Wrist

OBJECTIVETo perform linkage analysis and mutation screening in a Chinese family with familial hpertriglyceridemia (FHTG).

METHODSThirty-two family members including 12 hypertriglyceridemia patients participated in the study. Genotyping and haplotype analysis for 22 subjects were performed using short tandem repeat (STR) microsatellite polymorphism markers on 16 candidate genes and/or loci related to lipid metabolism. Two of the sixteen known candidate genes, APOA2 and USF1 were screened for mutation by direct DNA sequencing.

RESULTSNo linkage was found between the candidate genes/loci of APOA5, LIPI, RP1, APOC2, ABC1, LMF1, APOA1-APOC3-APOA4, LPL, APOB, CETP, LCAT, LDLR, APOE and the phenotype in this family. The two-point Lod scores (theta =0) were all less than-1.0 for all the markers tested. Linkage analysis suggested linkage to chromosome 1q23.3-24.2 between the disease phenotype and STR marker D1S194 with a two-point maximum Lod score of 2.44 at theta =0. Fine mapping indicated that the disease gene was localized to a 5.87 cM interval between D1S104 and D1S196. No disease-causing mutation was detected in the APOA2 and USF1 genes.

CONCLUSIONThe above mentioned candidate genes were excluded as the disease causing genes for this family. The results implied that there might be a novel gene/locus for FHTG on chromosome 1q23.3-1q24.2.

Adult ; Chromosome Mapping ; Chromosomes, Human, Pair 1 ; genetics ; Genetic Linkage ; Genotype ; Haplotypes ; Humans ; Hyperlipoproteinemia Type IV ; genetics ; Lod Score ; Male ; Middle Aged ; Pedigree

OBJECTIVETo map the candidate gene by linkage analysis in a Chinese family with autosomal dominant congenital retinaochoroidal coloboma.

METHODSA detailed clinical examination was performed for all patients in the family. The genomic DNA of all family members was extracted from peripheral blood leukocytes. Linkage analysis and genome-wide linkage screening was conducted using fluorescent detection of 398 microsatellite markers representing all autosomes at an average resolution of approximately 10 cM. Polymerase chain reaction was carried out to amplify all 398 microsatellite markers. The allele sizes were determined on ABI 3130-Avant genetic analyzer according to an internal size standard, and the results were analyzed using Genescan 3.1 and Genotyper 2.0 software.

RESULTSLinkage analysis showed the markers D2S2382-D2S301-D2S2244-D2S163 co-segregated with the disease locus in all affected members. The maximum Lod score was 3.01(D2S2382).

CONCLUSIONThe candidate region of the disease gene in the family was located in 2q34-2q35.

Asian Continental Ancestry Group ; Chromosome Mapping ; Coloboma ; genetics ; DNA Mutational Analysis ; Family ; Female ; Genetic Linkage ; Genotype ; Humans ; Lod Score ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; genetics ; Myopia ; genetics ; Pedigree ; Polymerase Chain Reaction