Structural and functional analysis of the HSP90AA1 gene: distribution of polymorphisms among sheep with different responses to scrapie.
Scrapie is a transmissible spongiform encephalopathy in sheep and goats. Susceptibility to this neurodegenerative disease is mainly controlled by point mutations at the PRNP locus. Other genes, apart from PRNP, have been reported to modulate resistance/susceptibility to scrapie. On the basis of several studies in Alzheimer and different transmissible spongiform encephalopathy models, HSP90AA1 was chosen as a putative positional and functional candidate gene that might be involved in the polygenic variance mentioned above. In the present work, the ovine HSP90AA1 gene including the promoter and other regulatory regions has been isolated and characterized. Several sequence polymorphisms have also been identified. FISH-mapping localized the HSP90AA1 gene on ovine chromosome OAR19q24dist, which was confirmed by linkage analysis. This chromosome region has been shown to include a quantitative trait loci (QTL) for scrapie incubation period in sheep. Expression analyses were carried out in spleen and cerebellum samples. No differences in the expression of the HSP90AA1 gene were found in any of these tissues (p > 0.05) between control and infected animal samples. Nevertheless, association analyses revealed that several polymorphisms in the 5' and 3' regions of the HSP90AA1 gene were differentially distributed among animals with different responses to scrapie infection. Thus, results presented here support the hypothesis that HSP90AA1 could be a positional and functional candidate gene modulating the response to scrapie in sheep.
Marcos-Carcavilla
Ane
A
Departamento de Mejora Genética Animal, INIA, Ctra La Coruña Km 7.5, Madrid, Spain. amarcos@inia.es
Calvo
Jorge H
JH
González
Carmen
C
Moazami-Goudarzi
Katayoun
K
Laurent
Pascal
P
Bertaud
Maud
M
Hayes
Hélène
H
Beattie
Anne E
AE
Serrano
Carmen
C
Lyahyai
Jaber
J
Martín-Burriel
Inmaculada
I
Serrano
Magdalena
M
D000818:Animals; D001483:Base Sequence; D002531:Cerebellum / Q000737:chemistry; D002874:Chromosome Mapping / Q000662:veterinary; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics* / Q000502:physiology; D008214:Lymphocytes / Q000737:chemistry; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D012608:Scrapie / Q000235:genetics*; D012756:Sheep / Q000145:classification / Q000235:genetics*; D012757:Sheep Diseases / Q000235:genetics*; D013045:Species Specificity; D013154:Spleen / Q000737:chemistry; D013329:Structure-Activity Relationship
D018841:HSP90 Heat-Shock Proteins