摘要:

We investigate properties of simple linkage disequilibrium mapping for five measures in the presence of mutation at the marker and/or the disease locus and of initial incomplete linkage disequilibrium. In contrast to the stimulation approach that Devlin and Risch used, we calculate the expected values of various linkage disequilibrium measures under different assumptions based on a framework for linkage disequilibrium mapping. These expected values clearly demonstrate the expected performance of these measures. We find that the impact of marker mutation on their performance depends on the magnitude of the mutation relative to the proximity of the marker (i.e. recombination fraction between the marker and the disease locus). In the presence of recurrent mutation at the marker and/or disease locus, the performance of all measures, including the robust one, depends on the marker allele frequency. The initial incomplete linkage disequilibrium could render all measures useless. These expected values also show clearly why in Devlin and Risch’s simulation some measures performed very badly under certain circumstance

ISSN:0001-5652    

DOI:10.1159/000154430

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

With more and more disease genes being mapped and/or cloned, there is a growing interest in dating the age of underlying mutations. The knowledge of the age of mutation is important to finely map disease genes by linkage disequilibrium mapping. It would also help us understand the origin, evolution, and dispersion of the mutant disease genes. Despite increasing interests in dating disease mutations, the development of appropriate statistical methods is largely fragmentary, and there is a lack of systematic treatment of the topic. We propose two classes of methods for estimating the age of mutant allele at the disease locus based on linked marker data. Our methods can not handle only single-locus marker data, but also multi-locus marker data as well. Moreover, our methods can be used even when the location of the disease locus is unknown, and/or when there are mutations at the marker or disease locus. We show that some previous results are special cases of our methods. We also derive a recursive equation previously obtained by Serre et al. [Hum Genet 1990;84:449-454] and provide an explicit solution to the equation. To illustrate our methods, we applied them to two groups of data sets, one is cystic fibrosis data collected from several European populations, and the other is data on several genetic diseases (diastrophic dysplasia, progressive myoclonus epilepsy, congenital chloride diarrhea, and Batten disease) all collected from the Finnish population. The former data set allows us to trace the origin and dispersion of the most common mutation for cystic fibrosis. The latter provides an opportunity to examine whether all mutations for these diseases have the same age.

ISSN:0001-5652    

DOI:10.1159/000154431

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

A guanine-adenine substitution was observed in exon 5 of the human transferrin (TF) gene. The nucleotide change led to an AvaI digestion site. Analysis of the segregation of the AvaI polymorphism and serum TF phenotypes indicated that an intragenic recombination occurred between the AvaI polymorphic site and the mutation site in the TF gene which determines the two common TF alleles, TF*C1 and TF*C2.

ISSN:0001-5652    

DOI:10.1159/000154432

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The transmission disequilibrium test uses association between marker alleles and dichotomous traits for precise genetic mapping while avoiding confounding due to population admixture. Here, the methodology is generalized from dichotomous traits to quantitative traits. The generalization is computationally straightforward and may be used with multiple alleles and with siblings. Parametric assumptions on the distribution of the quantitative traits are not needed. Environmental and demographic covariates may be incorporated into the analysis. The results of simulation studies that provide information about the power of the approach are reported.

ISSN:0001-5652    

DOI:10.1159/000154433

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Self-reports of disease from relatives are generally believed to be more detailed than those received from a family informant, although differential participation may exist among the relatives who provide information. To investigate the potential for differential participation, we requested permission to contact relatives of mothers (informants) who had provided family history information for a population-based case-control study of orofacial clefts. Birth defect and cancer self-reports were received from 345 (65.6%) case and 380 (68.8%) control relatives. Participants and nonparticipants differed little by type (maternal or paternal) or degree of relationship. Informants, however, were more likely to permit contact with relatives who were maternal, first-degree and female. Relatives appeared willing to provide self-reports, although the potential for differential selection introduced by informants should be considered.

ISSN:0001-5652    

DOI:10.1159/000154434

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0001-5652    

DOI:10.1159/000154435

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0001-5652    

DOI:10.1159/000154436

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0001-5652    

DOI:10.1159/000154437

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0001-5652    

DOI:10.1159/000154429

出版商:S. Karger AG    

年代:1997

数据来源: Karger