Evidence of a Major Gene From Bayesian Segregation Analyses of Liability to Osteochondral Diseases in Pigs

Abstract

Bayesian segregation analyses were used to investigate the mode of inheritance of osteochondral lesions (osteochondrosis, OC) in pigs. Data consisted of 1163 animals with OC and their pedigrees included 2891 animals. Mixed-inheritance threshold models (MITM) and several variants of MITM, in conjunction with Markov chain Monte Carlo methods, were developed for the analysis of these (categorical) data. Results showed major genes with significant and substantially higher variances (range 1.384-37.81), compared to the polygenic variance (s 2 u ). Consequently, heritabilities for a mixed inheritance (range 0.65-0.90) were much higher than the heritabilities from the polygenes. Disease allele frequencies range was 0.38-0.88. Additional analyses estimating the transmission probabilities of the major gene showed clear evidence for Mendelian segregation of a major gene affecting osteochondrosis. The variants, MITM with informative prior on s 2 u , showed significant improvement in marginal distributions and accuracy of parameters. MITM with a ''reduced polygenic model'' for parameterization of polygenic effects avoided convergence problems and poor mixing encountered in an ''individual polygenic model.'' In all cases, ''shrinkage estimators'' for fixed effects avoided unidentifiability for these parameters. The mixed-inheritance linear model (MILM) was also applied to all OC lesions and compared with the MITM. This is the first study to report evidence of major genes for osteochondral lesions in pigs; these results may also form a basis for underpinning the genetic inheritance of this disease in other animals as well as in humans.

Genetic analysis of insect bite hypersensitivity (summer eczema) in Icelandic horses

“…It is generally not recommended to apply an animal model in the context of categorical traits and single observation per animal (e.g. Wang, 1988), but Kadarmideen and Janss (2005) reported promising results from analyses of binary traits with a reduced animal model. Therefore, an attempt was made to analyse summer eczema as an all-or-none trait, assuming a reduced animal model on the liability scale, but unrealistically high heritabilities were obtained.…”

Hereditary hydrocephalus internus in a laboratory strain of golden hamsters (Mesocricetus auratus)

“…Accordingly, point estimates of unknown parameters are not derived, but rather estimates of the posterior density for unknown parameters. The iBay (2006) package was recently used to evaluate the contribution of a major locus to osteochondral diseases in pigs (Kadarmideen and Janss, 2005), where a more complete outline of the MCMC approach is detailed. The goal of this strategy was to simultaneously estimate the posterior density for a polygenic contribution to hydrocephalus along with the contributions of a putative Mendelian locus.…”

Bayesian analysis of genetic backgrounds of twinning rate in Thoroughbred horses

“…A mixed inheritance threshold model de-scribed among others by Morton and McLean (1974) and recently by Kadarmideen and Janss (2005) was used for the analysis of the data. The model has the following form: u = Xß+ZWµ+Za+e where: u (n x 1) is a vector of liability (unobserved variable), X (n x b) and Z (n x q) are known incidence matrices, W (q x 3) is a matrix assigning one of the three possible genotypes AA, Aa and aa to individuals,…”

“…The mixing properties of Gibbs sampling in the threshold model are rather poor. To avoid the discrepancy of the whole process an additional assumption about the additive variance component seems to be necessary (Kadarmideen and Janss, 2005). In the presented studies it was assumed that …”