Page 11 - L. Genetics and genomics
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Absence of single nucleotide polymorphisms (SNPs)
in the open reading frame (ORF) of the prion protein gene (PRNP)
in a large sampling of various chicken breeds
Sae-Young Won, Byung-Hoon Jeong
Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea
Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju 54896, Republic of Korea
ABSTRACT INTRODUCTION
Prion diseases are zoonotic diseases with a broad infection Prion diseases are zoonotic diseases caused by the
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spectrum among mammalian hosts and are caused by the misfolded prion protein (PrP ) derived from the normal prion
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misfolded prion protein (PrP ) derived from the normal prion protein (PrP ) and have a broad infection range in mammalian
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protein (PrP ), which encodes the prion protein gene (PRNP). hosts, including ruminants and humans. To date, normal
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Currently, although several prion disease-resistant animals functions of PrP and tandem repeat domains (octapeptide in
have been reported, a high dose of prion agent inoculation mammals and hexapeptide in birds) are well known and
triggers prion disease infection in these disease-resistant conserved in both mammals and birds, respectively.
animals. However, in chickens, natural prion disease-infected In mammals, several prion disease-associated SNPs have
cases have not been reported. So, investigation of the been reported in prion disease-susceptible species, including
chicken, which have shown perfect resistance to prion humans, sheep and goats. However, dog, which is known as
disease, could improve for understanding the mechanism of Dekalb White Ogolgye prion disease resistant animal, showed very little
perfect prion-disease resistance. Here, we investigated the polymorphisms in the PRNP ORF and horse has only one
genetic characteristics of the open reading frame (ORF) of the SNP in the ORF of the PRNP gene.
chicken PRNP gene in a large sampling of various chicken Our previous study indicated that chickens lack SNPs and
breeds. We found only tandem repeat deletion have only one insertion/deletion polymorphism located on the
polymorphisms of the chicken PRNP ORF in the 4 chicken hexapeptide repeat domain in the prion protein. However, in a
breeds including 106 Dekalb White, 100 Ross, 98 Ogolgye and study performed with only one chicken breed, Dekalb White,
100 Korean native chickens. In addition, the distribution of it was unclear whether this is a genetic characteristic of
chicken insertion/deletion polymorphisms was significantly chickens or a characteristic of a chicken breed, Dekalb White.
different among the 4 chicken breeds. Finally, we found We confirmed the genetic polymorphism, genotype and allele
chickens lack SNPs in the ORF of the prion protein. In this of the chicken PRNP gene in 4 chicken breeds, including
study, we found that the absence of SNPs in the chicken Dekalb White, Ross, Ogolgye and Korean native chickens.
PRNP ORF is a notable feature of animals with perfect Lastly, we investigated and compared SNPs of prion disease-
resistant to prion disease. Ross Korean native chickens susceptible species and prion disease-resistant species.
RESULTS
Table. 1 Comparison of genotype and allele distributions of chicken PRNP c.163_180delAACCCAGGGTACCCCCAT (p.55_60delNPGYPH) polymorphism
in 4 chicken breeds
Genotype frequency, n (%) Allele frequency, n (%)
Breeds Total, n P-value P-value HWE Ref
WT/WT WT/DEL DEL/DEL WT DEL
Octapeptide repeat domain
Dekalb White 106 13 (12.3) 89 (84) 4 (3.7) ― 115 (54.2) 97 (45.8) ― <0.0001 (Kim et al., 2018)
Ross 100 84 (84) 16 (16) 0 (0) <0.0001 184 (92) 16 (8) <0.0001 0.3845 This study
Ogolgye 100 68 (68) 31 (31) 1 (1) <0.0001 167 (83.5) 33 (16.5) <0.0001 0.2112 This study
Octapeptide repeat domain
Korean native chickens 100 82 (82) 17 (17) 1 (1) <0.0001 181 (90.5) 19 (9.5) <0.0001 This study
Table. 2 Genotype and allele frequencies of the chicken PRNP c.268_269insC polymorphism in 4 chicken breeds
Octapeptide repeat domain
Genotype frequency, n (%) Allele frequency, n (%)
Breeds Total, n P-value P-value HWE Ref
WT/WT WT/DEL DEL/DEL WT DEL
Dekalb White 106 102 (96.2) 4 (3.8) 0 (0) ― 208 (98.1) 4 (1.9) ― 0.8431 (Kim et al., 2018)
Octapeptide repeat domain
Ross 100 100 (100) 0 (0) 0 (0) 0.122 200 (100) 0 (0) 0.1238 NA This study
Ogolgye 100 100 (100) 0 (0) 0 (0) 0.122 200 (100) 0 (0) 0.1238 NA This study
Korean native chickens 100 100 (100) 0 (0) 0 (0) 0.122 200 (100) 0 (0) 0.1238 NA This study
Octapeptide repeat domain
Table. 3 Haplotype frequencies of two PRNP polymorphisms in 4 chicken breeds
c.163_180del
Haplotypes c.268_269ins C Dekalb White Ross Ogolgye Korean native chickens
AACCCAGGGTACCCCCAT
Hexapeptide repeat domain
ht 1 WT WT 115 (54.2) 184 (92) 167 (83.5) 181 (90.5)
Fig. 1 Distribution of the single nucleotide polymorphisms (SNPs) at ht 2 DEL WT 93 (43.9) 16 (8) 33 (16.5) 19 (9.5)
coding region of the prion protein gene (PRNP) in various species. ht 3 DEL INS 4 (1.9) 0 (0) 0 (0) 0 (0)
Previously reported SNPs at coding region of PRNP gene in human,
sheep, goats, cattle, horse and chickens. Edged horizontal bar indicates P-value ― <0.0001 <0.0001 <0.0001
the length of amino acids. Gray boxes indicate tandem repeat domains Ref (Kim et al., 2018) This study This study This study
CONCLUSION
Table. 4 Distribution of the single nucleotide polymorphisms (SNPs) at the open reading frame (ORF) of the
prion protein gene (PRNP) in various species
◆The present study surveyed chicken PRNP polymorphisms in large samples of 4 chicken breeds,
Species Polymorphisms Total, n Ref
Dekalb white, Ross, Ogolgye and Korean native chickens.
G54S, P68P, G114 V, G127 V, M129 V, G142S, R148H, (Jeong et al., 2014,
N171S, D178N, V180I,
Human 20 Lloyd et al., 2011, ◆We found only tandem repeat deletion polymorphisms and compared the genotype and allele
T183A, T188K, E200K, V203I, R208H, V210I, E211Q, E219K, Jeong et al., 2004)
M232R, P238S distribution of tandem repeat polymorphisms among 4 chicken breeds. We confirmed that
S98R, Q101R, M112 T, A116P, A116E, G127S, A136V, A136T, chickens have significantly different genotypes and allele distributions of tandem repeat
M137 T, S138R, (Guan et al., 2011, polymorphisms among 4 chicken breeds.
L141F, I142K, H143R, G145 V, N146S, D147E, Y152F, Frootan et al., 2012,
Sheep 31
R154H, P168L, Q171R, Seabury et al., 2004, ◆Finally, we found significant differences in the number of PRNP SNPs between prion disease-
Q171H, Q171K, Y172D S173 N, Q175R, N176K, V179E, Ekateriniadou et al., 2007)
N184H, Q189L, R231R, L237 L susceptible species and prion disease-resistant species. To the best of our knowledge, no SNP
has been identified in the chicken PRNP gene thus far.
W18R, V21A, L23P, G37 V, P42P, G49S, Q101R, Q101Q,
W102G, K107K,
T110P, V125 V, G127S, L133Q, M137I, S138S, I142M, I142T,
I42I, H143R, (Vaccari et al., 2009, REFERENCES
Goats 41
N146D, N146S, R151H, R154H, P168Q, V179 V, D181D, Kim et al., 2019)
T194P, F201F, T202 T,
K207K, R211Q, R211G, I218L, T219 L, Q220H, Q222K, ◆Kim YC, Jeong MJ, Jeong BH. The first report of genetic variations in the chicken prion protein
Q222Q, G232 W, G232G, S240P gene. Prion. 2018;12(3–4):197–203.
K3T, S8S, V21E, S46I, N50S, P54S, G58G, G66G, G67S,
W68R, G73A, Q78Q, (Choi et al., 2012, ◆Sanchez-Garcia J, Fernandez-Funez P. D159 and S167 are protective residues in the prion
G83G, K117K, M145 V, S146 N, S154S, S154 N, Y156C, protein from dog and horse, two prion-resistant animals. Neurobiol Dis. 2018;119:1–12.
Jeong et al., 2005,
Cattle Y174C, N184D, N185 N, 38 Msalya et al., 2009,
N192 N, V200F, V200A, T204A, K205E, F209S, T210 T, Zhao et al, 2010) ◆Prusiner SB. The prion diseases. Brain Pathol. 1998;8:499–513.
T212A, K215R, M216 T, ◆Choi S, Woo HJ, Lee J. Sequence variations of the bovine prion protein gene (PRNP) in native
Q223H, I244V, L245F, P249P, I252F, L253P
Korean Hanwoo cattle. J Vet Sci. 2012;13:127–37
Horse N175K 1 (Kim et al., 2018)
(Kim et al., 2018, ◆Ricci A, Bolton D, Chemaly M, Davies R. Genetic resistance to transmissible spongiform
Chickens Not Detected 0
This study) encephalopathies (TSE) in goats. EFSA J. 2017;15:4962.
