No abstract available.
DNA* ; Genetic Linkage*

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

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: To assess the value of Karyomapping for the prenatal diagnosis of facioscapulohumerial muscular dystrophy type 1 (FSHD1). METHODS: Peripheral blood and chorionic villi samples were collected from five families affected with FSHD1. Linkage-based diagnosis was carried out by using the Karyomapping method. Diagnosis for two fetal samples was carried out with the next-generation optical mapping system. RESULTS: The results of Karyomapping showed that three fetuses inherited the risky 4q35 region of the proband and two fetuses did not. The fetuses of families 1 and 2 received further diagnosis by the next-generation optical mapping system, and the results were consistent with those of Karyomapping. CONCLUSION Karyomapping has enabled prenatal diagnosis for the five families affected with FSHD1. The method was faster and simpler compared with conventional strategies, though its feasibility still needs further validation. Since there were no SNP loci designed on the Karyomap chip for the DUX4 gene and its 3' flanking regions, misjudgment due to chromosomal recombination could not be completely eliminated. The accuracy of this method still needs further validation.
Female ; Genetic Linkage ; Humans ; Muscular Dystrophies ; Pregnancy ; Prenatal Diagnosis

The first genetic linkage map of Salvia miltiorrhiza was constructed in 94 F1 individuals from an intraspecific cross by using simple sequence repeat (SSR), sequence-related amplified polymorphism (SRAP) and inter-simple sequence repeat (ISSR) markers. A total of 93 marker loci in the linkage map, consisting of 53 SSR, 38 SRAP and 2 ISSR locus were made up of eight linkage groups, covered a total length of 400.1 cm with an average distance of 4.3 cm per marker. The length of linkage groups varied from 3.3 -132 cm and each of them included 2-23 markers, separately. The result will provide important basis for QTL mapping, map-based cloning and association studies for commercially important traits in S. miltiorrhiza.
Chromosome Mapping ; Genetic Linkage ; Genetic Markers ; Microsatellite Repeats ; Polymorphism, Genetic ; Salvia miltiorrhiza ; genetics

Considering the great progress in the field of molecular genetics research on schizophrenia, this review is aimed at discussing advances in genes of schizophrenia and their pathophysiological implications for the disorder.
Genetic Linkage ; Genetic Predisposition to Disease ; genetics ; Humans ; Polymorphism, Genetic ; Schizophrenia ; genetics

Approaches to the study of the genetic basis of common complex diseases and their clinical applications are considered. Monogenic Mendelian inheritance in such conditions is infrequent but its elucidation may help to detect pathogenic mechanisms in the more common variety of complex diseases. Involvement by multiple genes in complex diseases usually occurs but the isolation and identification of specific genes so far has been exceptional. The role of common polymorphisms as indicators of disease risk in various studies is discussed.
Genetic Diseases, Inborn ; genetics ; Genetic Predisposition to Disease ; Genetic Techniques ; Humans ; Inheritance Patterns ; Linkage Disequilibrium ; Models, Genetic ; Polymorphism, Genetic ; Risk Factors

OBJECTIVETo explore factor IX gene mutations and molecular mechanism of haemophilia B in 3 unrelated families.

METHODSThe activated partial thromboplastin time (APTT) and FIX activity (FIX: C) assay were used for phenotypic diagnosis. The STR loci gene polymorphisms for genetic linkage analysis in the patients and their family members were assayed. All of the 8 exons and the exon-intron boundaries of FIX gene were amplified by polymerase chain reaction (PCR) and direct sequencing.

RESULTS AND CONCLUSIONMutations were found in the FIX gene of the propositi. Proband 1 had a G22119A mutation in exon 6, proband 2 a G7392C mutation in exon 2 and proband 3 a T32685C mutation in exon 8.

DNA Mutational Analysis ; Factor IX ; genetics ; Genetic Linkage ; Hemophilia B ; genetics ; Humans ; Mutation ; Pedigree ; Polymorphism, Genetic

OBJECTIVEX-linked spondyloepiphyseal dysplasia tarda (SEDL) is a rare osteochondrodysplasia caused by mutations of SEDL gene, which usually onset in late childhood without systemic complications. In this study, we have provided prenatal diagnosis for an affected family with a combined strategy including direct sequencing, fetal-sex identification and microsatellite linkage analysis.

METHODSTwo amniotic fluid samples from carrier gravida and 7 blood samples from individuals in this SEDL pedigree were obtained. Genomic DNA was extracted from the samples using standard phenol-chloroform method. SRY and AMEL genes were employed to assess fetal sex. Microsatellite DXS16 was genotyped for linkage analysis. A pathogenic mutation of the SEDL gene was identified by bi-directionally direct sequencing of the third exon as well as its exon/intron boundaries.

RESULTSTwo male fetuses were confirmed by fetal-sex assessment. The mutation of the SEDL gene was identified as a nucleotide substitution of the splice acceptor site in intron 2, IVS2-2A>C. DNA sequencing indicated that one fetus is hemizygote carrying the mutation, whilst another is not a carrier. Linkage analysis was identical with the sequencing results. Follow-up also confirmed the result of prenatal diagnosis.

CONCLUSIONFetal-sex assessment combined with microsatellite linkage analysis and bi-directionally direct sequencing is a more accurate and ready strategy for prenatal diagnosis of families affected with SEDL.

Genetic Diseases, X-Linked ; diagnosis ; Genetic Linkage ; Humans ; Male ; Osteochondrodysplasias ; diagnosis ; Prenatal Diagnosis ; Sequence Analysis, DNA

OBJECTIVESTo identify the possible relationship between polymorphisms of D17S1878 and D17S932 on the Chromosome 17 and risk of essential hypertension (EH).

METHODSThe polymorphisms of D17S1878 and D17S932 were genotyped using Genetic Analyzer in 325 subjects from 67 Chinese families with EH in Liaoning province. The polymorphisms of D17S1878 and D17S932 sites were genotyped using Genetic Analyzer and GeneScan Software; PHASE2.1 Software was used in hyplotype analysis and affected sib pair analysis was used in linkage analysis.

RESULTS61 hyplotypes were found in the study population with 272 hypertensive and 53 normotensive subjects and the frequency of haplotype H1 [(CA)(18)/(CA)(11)] in the hypertensive (15.4%) was significantly higher than that in the normotensive (6.3%, P < 0.05). Affected sib pair analysis could be applied in 180 subjects, the t values of the D17S1878 and D17S932 were 1.88 and 3.95, respectively (both P < 0.05) suggesting that the transitivity and consistency of the D17S1878 and D17S932 in sib pairs from the pedigrees were higher than expected (25%).

CONCLUSIONThe polymorphisms of D17S1878 and D17S932 were possibly linked with predisposing genes of essential hypertension.

Chromosomes, Human, Pair 17 ; Genetic Linkage ; Genotype ; Humans ; Hypertension ; epidemiology ; Polymorphism, Genetic