Biomedical subjects

M Xiong

Publications and source records attributed to M Xiong.

75 records · Page 5Linked to original sources

PubMedDate not supplied

The power of linkage detection by the transmission/disequilibrium tests.

Despite growing interest in the use of transmission/disequilibrium test (TDT)-type analysis in association studies, there has been surprisingly scant attention paid to the issues as to what factors affect the power of the TDT for linkage detection. We demonstrate in this paper that the power is a function of several genetic parameters including the recombination fraction, penetrance, the age of mutant disease allele, marker allele frequency, recurrent mutation rates at marker and/or disease locus, and initial linkage disequilibrium. In general, TDT has greater power to detect linkage for a 'recessive'-type model than for a 'dominant'-type model. Its power also is higher when there is greater differential in marker allele frequency between disease and normal chromosomes. And since the presence of marker mutation and/or recurrent mutation at the disease locus, or the age of disease mutation, or the initial incomplete linkage disequilibrium, all hasten the process to reach linkage equilibrium, all of them can affect the power of TDT to detect linkage. The effect of marker mutation rate or the mutation rate at the disease locus can be minimal if mutation rates are low. The results on the impact of recombination fraction and of age of mutation on the power of TDT in linkage detection seem to be disheartening for gene mappers of complex diseases: for a disease with small genetic influence, a vastly large sample size is needed to detect the linkage, if the marker is not very close to the disease locus. This is particularly true if the disease is 'old'.

Chromosome Mapping↗

PubMedDate not supplied

Genes preserved in relatives.

The genes of an individual are said to be preserved in his relatives if they possess, collectively, all copies of his genes. We present a method for computing the probability that an individual's genes are preserved in his relatives. Using this method, we compute gene preservation probabilities (up to three linked loci) for a variety of relationships for humans and for haplodiploid species. The results suggest that some widely held notions in ethology and sociobiology seem to be questionable. From the gene preservation viewpoint, two brothers are far from enough to justify the sacrifice of one's own life, because the probability that an individual's genes are preserved in his two siblings is dismally small. The precise probability that an individual's genes are all preserved in a group of his relatives depends on the precise specification of the pedigree structure. We also demonstrate that, for a hymenopteran female, there is no practical difference, in terms of gene preservation probability, between helping her sisters to breed and breeding her own offspring. In fact, since the genes of her sister will be either lost or preserved in her nieces/nephews, it is more appropriate to compare the probability of preserving her genes through her own offspring with that through her nieces/nephews. We show that her chance of preserving all her genes is much higher if she chooses to breed her own offspring instead of helping her sister.

Animals↗

PubMedDate not supplied

Estimating the age of mutant disease alleles based on linkage disequilibrium.

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.

Alleles↗