Gamete-competition models.
The gamete-competition model is an application of the Bradley-Terry model for ranking of sports teams. If allele i of a marker locus is assigned parameter taui>0, then the probability that a parent with heterozygous genotype i/j transmits allele i is Pr(i/j-->)=tau(i)/(tau(i) + tau(j). Mendelian segregation corresponds to the choice tau(i)=1 for all i. To test whether Mendelian segregation is true, one can estimate the tau(i) from pedigree data and perform a likelihood-ratio test under the constraint that one tau(i) equals 1. Although this procedure generates an interesting method for performance of segregation analysis with a marker locus, its real promise lies in generalization of the transmission/disequilibrium test. Quantitative as well as qualitative outcomes can be considered. The gamete-competition model uses full pedigree data and gives an estimate of the strength of transmission distortion to affected children for each allele. Covariates are incorporated by rewriting of tau(i)=exp(beta(t)x(k)), where beta is a parameter vector and xk is a covariate vector for the kth transmitted gamete. Examples of covariates include disease-severity indicators for the child, sex of the child, or repeat number for tandem-repeat alleles.
Sinsheimer
J S
JS
Department of Biomathematics, UCLA School of Medicine, Los Angeles, CA, 90095, USA. janet@sunlab.ph.ucla.edu
Blangero
J
J
Lange
K
K
D018528:ATP-Binding Cassette Transporters; D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods* / Q000706:statistics & numerical data; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics; D005854:Germ Cells / Q000378:metabolism / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008957:Models, Genetic; D010290:Parents; D010375:Pedigree; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010733:Phosphoglucomutase; D010750:Phosphoproteins / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D019655:Quantitative Trait, Heritable; D011955:Receptors, Drug / Q000235:genetics; D012727:Sex Characteristics; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D010750:Phosphoproteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D007703:Peptidyl-Dipeptidase A; C488050:PGM1 protein, human; D010733:Phosphoglucomutase