Genome-wide search for markers associated with bovine spongiform encephalopathy.
A genome-wide search for markers associated with BSE incidence was performed by using Transmission-Disequilibrium Tests (TDTs). Significant segregation distortion, i.e., unequal transmission probabilities of alleles within a locus, was found for three marker loci on Chromosomes (Chrs) 5, 10, and 20. Although TDTs are robust to false associations owing to hidden population substructures, it cannot distinguish segregation distortion caused by a true association between a marker and bovine spongiform encephalopathy (BSE) from a population-wide distortion. An interaction test and a segregation distortion analysis in half-sib controls were used to disentangle these two alternative hypotheses. None of the markers showed any significant interaction between allele transmission rates and disease status, and only the marker on Chr 10 showed a significant segregation distortion in control individuals. Nevertheless, the control group may have been a mixture of resistant and susceptible but unchallenged individuals. When new genotypes were generated in the vicinity of these three markers, evidence for an association with BSE was confirmed for the locus on Chr 5.
Hernández-Sánchez
Jules
J
Roslin Institute (Edinburgh), Roslin, Midlothian, EH25 9PS, UK. Jules.Hernandez@bbsrc.ac.uk
Waddington
Dave
D
Wiener
Pamela
P
Haley
Chris S
CS
Williams
John L
JL
D000818:Animals; D002417:Cattle; D002874:Chromosome Mapping; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D016678:Genome; D007113:Immunity, Innate / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D006113:United Kingdom
D005819:Genetic Markers