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ASSOCIATION OF PrP GENE WITH NEONATAL LAMB SURVIVAL
Rami M. Sawalhaa, Susan Brotherstonea,b, Joanne Coningtona, Beatriz Villanuevaa
a
Scottish Agricultural College, West Mains Road, Edinburgh EH9 3JG, UK, bSchool of
Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
In scrapie-affected flocks, animals with susceptible PrP genotypes have been shown to have
a higher incidence of death from unknown causes than animals with resistant genotypes.
Thus, the persistence of PrP alleles associated with scrapie susceptibility suggests that the
gene has a pleiotropic effect or is linked to other genes that affect fitness in the absence of
scrapie. The objective of this study was to investigate a possible association of the PrP gene
with lamb survival. All lambs that are alive at weaning (ca. 120 d) and born from 1999 to
2004 and dead lambs born in 2002 and 2004 in two Scottish Blackface flocks were
genotyped for polymorphisms at codons 136, 154 and 171 of the PrP gene. Four survival
traits were considered: viability at birth (dead or alive at 24 h of birth; 3,955 lambs),
survival from 1 d to 14 d (3,743 lambs), survival from 15 d to 120 d (3,673 lambs) and
survival from 121 d to 180 d (6,777 lambs). Viability at birth was analyzed using a
complementary log-log link function and postnatal survival traits were analyzed using a
Weibull proportional hazard model. The models adjusted for significant biologicallysensible effects and included a random sire effect to account for polygenic effects. The
effect of the PrP genotype was estimated by including it as a fixed factor in the model. The
hazard ratios for the PrP genotypes were compared using the Bonferroni corrected
likelihood ratio test. It was found that the ARR allele (known for conferring the highest
resistance to classical scrapie) is significantly associated with a lower postnatal lamb
survival rate than the ARQ allele which is known to be associated with elevated risk of
scrapie susceptibility. Lambs with ARR/ARQ or ARQ/ARQ genotypes were found to have
a 2 to 3 times lower postnatal hazard rate of mortality than lambs with ARR/ARR or
ARR/AHQ genotypes (known for their high resistance to scrapie). The higher survival rate
of lambs carrying the scrapie-susceptible ARQ allele in scrapie-free flocks may explain the
persistence and the high frequency of this allele in sheep populations despite centuries of
natural selection against scrapie.
Key words: Scrapie, PrP, association, survival, sheep