Prion sequence polymorphisms and chronic wasting disease resistance in Illinois white-tailed deer (Odocoileus virginianus)

Figures & data

Figure 1 Nucleotide and amino acid database consensus sequence and polymorphisms observed in Illinois white-tailed deer. Numbers indicate the nucleotide or deduced amino acid sequence from a consensus. Observed frequency (# of polymorphic alleles/total # of alleles* 100) of polymorphisms and domains within the prion protein are also indicated.

Figure 2 Probability of CWD as predicted by the number of polymorphic alleles. Total polymorphisms, silent polymorphisms, coding polymorphisms and total polymorphisms omitting locus 153 were used as independent variables in separate logistic regression models with CWD as the outcome variable. Odds ratios were estimated using the number of heterozygous and homozygous SNP summed across all loci. Coding for locus 153 was reversed because wild-type alleles conferred susceptibility (2 = homozygous for the consensus genotype, 1 = heterozygous, 0 = homozygous for the polymorphism), which resulted in a higher predicted probability of CWD than in a model omitting locus 153.

Figure 3 Distribution of coding polymorphisms Q95H and G96S. Bars represent the percent of sampled population of the indicated genotype within disease status. Distribution of coding polymorphisms for sampled populations of Illinois deer are represented by open bars. Distribution of polymorphisms for Wisconsin deer (hatched bars) were calculated from published results.12

Table 1 Ratio of observed and expected allele frequencies for nucleotide polymorphisms

Allele	Total frequency	Frequency in negative population	Frequency in positive population	Odds ratio	Wald 95% confidence internal
60C	92.1	88.8	97.4	0.21	0.07–0.62
*60T	7.9	11.2	2.6
153C	88.5	92.5	82.2	2.66	1.41–5.03
*153T	11.5	7.5	17.8
243T	98.5	98.3	98.6	ns
243A	1.5	1.7	1.4
285A	93.9	91.7	98.0	0.21	0.06–0.72
* 285C	6.1	8.3	2.0
286G	86.2	79.6	96.7	0.13	0.05–0.34
* 286A	13.8	20.4	3.3
378G	99.7	99.6	100	ns
378A	0.3	0.4	0
438C	95.7	95.0	96.7	ns
438T	4.3	5.0	3.3
555C	57.6	53.8	63.8	0.66	0.43–1.00
*555T	42.4	46.2	36.2
676C	98.7	97.9	100.0	ns
676A	1.3	2.1	0

Bold text indicates loci where nucleotide sequence resulted in a change of expressed protein; other polymorphisms were synonymous.

* Indicates a significant association (p < 0.05) between allele and CWD status using chi-square expected frequency for presence/absence of each allele obtained from PROC FREQ. Odds ratios were obtained with PROC LOGISTIC using each allele as a class variable regressed against CWD as an outcome. Only odds ratios with significant (p < 0.05) parameter estimates are reported. Polymorphisms with non-significant odds ratios and 95% confidence limits overlapping 1 are denoted by ns.

Table 2 Ratio of observed and expected genotype frequencies for nucleotide polymorphisms

Locus	Genotype	n	Frequency in negatives	Frequency in positives	Odds ratio	Wald 95% confidence interval
*60**	CC	166	78.4	94.7
	CT	29	20.8	5.3	0.21	0.07–0.63
	TT	1	0.8	0	nc
*153	CC	155	85.8	68.4
	CT	37	13.3	27.6	2.60	1.25–5.40
	TT	4	0.8	4.0	5.94	0.60–58.52
243	TT	191	97.5	97.4
	TA	4	1.7	2.6	ns
	AA	1	0.8	0	ns
* 285 **	AA	173	83.3	96.1
	AC	22	15.8	3.9	0.22	0.06–0.76
	CC	1	0.8	0	nc	nc
* 286	GG	153	68.3	93.4
	GA	32	22.5	6.6	0.21	0.08–0.59
	AA	11	9.2	0	nc	nc
378	GG	195	99.2	100
	GA	1	0.8	0	ns
	AA	0	0	0	ns
438	CC	179	90	93.4
	CT	17	10	6.6	ns
	TT	0	0	0	ns
*555	CC	65	31.6	35.5
	CT	96	44.2	56.6	1.14	0.60–2.16
	TT	35	24.2	7.9	0.29	0.11–0.80
676	CC	192	96.7	100
	CA	3	2.5	0	ns
	AA	1	0.8	0	ns

Bold text indicates loci where nucleotide sequence resulted in a change of expressed protein; other polymorphisms were synonymous.

* Indicates a significant association (p < 0.05) between each genotype and CWD status using chi-square expected frequency obtained from PROC FREQ. Odds ratios were obtained with PROC LOGISTIC using each SNP as a class variable regressed against CWD as an outcome. Only odds ratios with significant (p < 0.05) parameter estimates are reported. Polymorphisms with non-significant odds ratios and 95% confidence limits overlapping 1 are denoted by ns.

** Indicates loci with significant linkage disequilibrium (p < 0.01). “nc” indicates no cases so odds ratios were not calculable.

Table 3 Reconstructed frequencies of common haplotypes for CWD positive animals and controls

Haplotype definition	Frequency in (-) animals	Frequency in (+) animals
CCTAGGCCC	33.0	39.8
CCTAGGCTC	28.1	31.6
CCTAAGCTC	12.2	2.6
CTTAGGCCC	10.3	16.3
TCTCGGCCC	4.6	0.0
CCTAGGTCC	3.9	2.8
TCTAGGCCC	1.4	1.8
TCTAGGCCA	1.3	0.0
CCTCGGCCC	1.1	1.5

Haplotypes were generated from unphased genotypes with the Bayesian (ELB) algorithim in Phase ver 2.1. The distribution of haplotype frequencies was significantly different between CWD positive and CWD negative animals (p < 0.01). Only haplotypes with frequencies greater than 1% are reported.

Johnson C, Johnson J, Vanderloo JP, Keane D, Aiken JM, McKenzie D. Prion protein polymorphisms in white-tailed deer influence susceptibility to chronic wasting disease. J Gen Virol 2006; 87:2109 - 2114

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