title: A trisomic transmission disequilibrium test.
abstract: Certain congenital disorders that are rare in the general population are quite common in individuals with trisomic conditions. For example, complete atrioventricular septal defect occurs in about 20% of individuals with Down syndrome, an approximately 500-fold increase in risk as compared to individuals without Down syndrome. Genetic variation on the chromosome involved in the trisomy may affect susceptibility to these trisomy-specific disorders. That is, increased dosage of a variant may be directly involved in increasing the risk of a disorder, or it may be indirectly involved by causing up- or downregulation of other genes. As in standard disomic gene-mapping, one can search for genes using linkage or association methods. Within association methods, one can consider case-control methods or family-based control methods such as the transmission disequilibrium test (TDT). Most gene-mapping methods need to be substantially redesigned for use with trisomic data. In this paper, we present a "trisomic TDT", a statistical method of testing for nonrandom transmission of alleles from parents to trisomic children. We demonstrate the method on a dataset of parent-child trios in which the child has Down syndrome.
authors.affiliation: Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Xu
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Kerstann
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sherman
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Eleanor
authors.initials: E
authors.lastname: Feingold
mesh_terms: D000328:Adult; D002648:Child; D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D004314:Down Syndrome / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005318:Fetal Heart / Q000378:metabolism; D005838:Genotype; D006330:Heart Defects, Congenital / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D016013:Likelihood Functions; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008432:Mathematical Computing; D008957:Models, Genetic; D015233:Models, Statistical; D009124:Muscle Proteins / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011336:Probability; D012984:Software; D014314:Trisomy / Q000235:genetics*
chemical_list: D009124:Muscle Proteins; C104671:SH3BGR protein, human