Positional cloning of gene(s) underlying a complex disease trait poses requirement of a highresolution linkage map between the disease locus and genetic marker loci. Recent researches have shown that this may be achie...Positional cloning of gene(s) underlying a complex disease trait poses requirement of a highresolution linkage map between the disease locus and genetic marker loci. Recent researches have shown that this may be achieved through appropriately modeling and screening linkage disequilibrium between the candidate marker locus and the major trait locus. However, these models were restricted to the circumstances where genotyping at the disease locus was feasible. The major limitations of pedigree-based linkage analyses were addressed in the light of positional cloning and positional candidate gene identification in humans. It summarizes the recent efforts in developing theories for fine-scale mapping of genes underlying complex genetic variations where the one-to-one relationship no longer exists between phenotype of the genetic disorders and the corresponding genotype.展开更多
Modeling linkage disequilibria (LD) between genes usually observed in admixed natural populations has been shown an effective approach in high-resolution mapping of disease genes in humans. A prerequisite to obtain ac...Modeling linkage disequilibria (LD) between genes usually observed in admixed natural populations has been shown an effective approach in high-resolution mapping of disease genes in humans. A prerequisite to obtain accurate estimation of recombination fraction between genesat a marker locus and the disease locus using the approach is a reliable prediction of the proportion of the admixture populations. The present study suggested the use of gene frequencies to predict the estimate of the admixture proportion based on the observation that the gene frequencies are much more stable quantities than the haplotype frequencies over evolution of the population. In this paper, we advanced the theory and methods by which the decay rate of nonlinear term of LD in admixed population may be used to estimate the recombination fraction between the genes. Theoretical analysis and simulation study indicate that, the larger the difference of gene frequencies between parental populations and the more closely the展开更多
Understanding linkage disequilibrium (LD) created in admixed population and the rate of decay in the disequilibrium over evolution is an important subject in population genetics theory and in disease gene mapping in h...Understanding linkage disequilibrium (LD) created in admixed population and the rate of decay in the disequilibrium over evolution is an important subject in population genetics theory and in disease gene mapping in human populations. The present study represents the theoretical investigation of effects of gene frequencies, levels of LD and admixture proportions of donor populations on the evolutionary dynamics of the LD of the admixed population. We examined the conditions under which the admixed population reached linkage equilibrium or the peak level of the LD. The study reveals the inappropriateness in approximating the dynamics of the LD generated by population admixture by the commonly used formula in literature. An appropriate equation for the dynamics isproposed. The distinct feature of the newly suggested formula is that the value of the nonlinear component of the LD remains constant in the first generation of the population evolution. Comparison between the predicted disequilibrium dynamics展开更多
文摘Positional cloning of gene(s) underlying a complex disease trait poses requirement of a highresolution linkage map between the disease locus and genetic marker loci. Recent researches have shown that this may be achieved through appropriately modeling and screening linkage disequilibrium between the candidate marker locus and the major trait locus. However, these models were restricted to the circumstances where genotyping at the disease locus was feasible. The major limitations of pedigree-based linkage analyses were addressed in the light of positional cloning and positional candidate gene identification in humans. It summarizes the recent efforts in developing theories for fine-scale mapping of genes underlying complex genetic variations where the one-to-one relationship no longer exists between phenotype of the genetic disorders and the corresponding genotype.
基金the National Key Basic Research Project ("973") and the National Natural Science Foundation of China (Grant No. 39725018).
文摘Modeling linkage disequilibria (LD) between genes usually observed in admixed natural populations has been shown an effective approach in high-resolution mapping of disease genes in humans. A prerequisite to obtain accurate estimation of recombination fraction between genesat a marker locus and the disease locus using the approach is a reliable prediction of the proportion of the admixture populations. The present study suggested the use of gene frequencies to predict the estimate of the admixture proportion based on the observation that the gene frequencies are much more stable quantities than the haplotype frequencies over evolution of the population. In this paper, we advanced the theory and methods by which the decay rate of nonlinear term of LD in admixed population may be used to estimate the recombination fraction between the genes. Theoretical analysis and simulation study indicate that, the larger the difference of gene frequencies between parental populations and the more closely the
基金This work was supported by the National "973" Key Basic Research Project and the National Natural Science Foundation of China (Grant No. 39725018).
文摘Understanding linkage disequilibrium (LD) created in admixed population and the rate of decay in the disequilibrium over evolution is an important subject in population genetics theory and in disease gene mapping in human populations. The present study represents the theoretical investigation of effects of gene frequencies, levels of LD and admixture proportions of donor populations on the evolutionary dynamics of the LD of the admixed population. We examined the conditions under which the admixed population reached linkage equilibrium or the peak level of the LD. The study reveals the inappropriateness in approximating the dynamics of the LD generated by population admixture by the commonly used formula in literature. An appropriate equation for the dynamics isproposed. The distinct feature of the newly suggested formula is that the value of the nonlinear component of the LD remains constant in the first generation of the population evolution. Comparison between the predicted disequilibrium dynamics
