First report of novel single nucleotide polymorphisms (SNPs) and genetic characteristics of the prion-like protein gene (PRND) in cynomolgus monkeys
Abstract
Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases caused by misfolded prion protein. The prion-like protein (Doppel), encoded by the prion-like protein gene (
PRND
), is linked to neurodegeneration and TSE susceptibility. While
PRND
polymorphisms have been studied in various species, their genetic features in non-human primates remain unexplored. Cynomolgus monkeys (
Macaca fascicularis
), which are genetically close to humans, are a valuable model to study the role of
PRND
polymorphisms in prion disease susceptibility. We performed polymerase chain reaction (PCR) to amplify the monkey
PRND
gene and investigated genetic polymorphisms in cynomolgus monkeys (
n
= 121). Genotype, allele, and haplotype frequencies, as well as linkage disequilibrium (LD), were analyzed to assess the genetic architecture of the population using Haploview (v4.2). Monkey
PRND
amino acid sequences were compared with those of several species using ClustalW. The effects of non-synonymous SNPs and the structural analysis of monkey Doppel were evaluated using
in silico
tools. We identified 15 novel genetic polymorphisms in the monkey
PRND
gene, including 12 variants located within the open reading frame (ORF), one in the upstream region, and two in the downstream region. In addition, LD analysis revealed several strong LD relationships among
PRND
polymorphisms in monkeys. ClustalW analysis showed that humans and monkeys shared the same
PRND
sequence length and…
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