Admixture mapping using interval transmission/disequilibrium tests.
Family-based studies of genetic association and linkage play a key role in mapping susceptibility genes of complex human diseases. Recent admixture between genetically differentiated populations can result in high levels of linkage disequilibrium even at far apart loci. This has been capitalized upon to reduce the burden of genotyping in a genomewide association scan. Here the authors describe an alternative approach for admixture mapping. The genome is divided into several non-overlapping intervals and the information of the markers in the same interval is integrated--the 'interval transmission/disequilibrium test' (ITDT). This method requires information in the form of the marker allele frequencies in the founding populations. However, computer simulations show that the performances of ITDT are hardly affected by imprecise allele-frequency information. Simulations also show that an interval-by-interval scan using ITDT perform much better than a conventional marker-by-marker scan using TDT, even under conditions where the admixture process occurred over many generations and the individuals in the admixed populations show considerable variation in admixture proportion. Hence the ITDT is a promising new genomewide scan method.
Lee
Wen-Chung
WC
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei. wenchung@ha.mc.ntu.edu.tw
Yen
Yu-Chun
YC
D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D005190:Family; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008957:Models, Genetic