A trisomic transmission disequilibrium test

Genet Epidemiol. 2004 Feb;26(2):125-31. doi: 10.1002/gepi.10302.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Child
  • Chromosome Mapping / statistics & numerical data*
  • Down Syndrome / epidemiology
  • Down Syndrome / genetics*
  • Female
  • Fetal Heart / metabolism
  • Genotype
  • Heart Defects, Congenital / epidemiology
  • Heart Defects, Congenital / genetics
  • Humans
  • Infant, Newborn
  • Likelihood Functions
  • Linkage Disequilibrium / genetics*
  • Male
  • Mathematical Computing
  • Models, Genetic*
  • Models, Statistical*
  • Muscle Proteins / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Probability
  • Software
  • Trisomy / genetics*


  • Muscle Proteins
  • SH3BGR protein, human