OMIA:000499-9544 : Hypercholesterolaemia in Macaca mulatta (Rhesus monkey)
Categories: Homeostasis / metabolism phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 1990
Cross-species summary: Hypercholesterolemia; see also OMIA 001160: Hyperlipidaemia
Molecular basis: Hummel et al. (1990) "identified a family of rhesus monkeys with members exhibiting a spontaneous hypercholesterolemia associated with a low density lipoprotein receptor (LDLR) deficiency. By using the polymerase chain reaction, we now show that the affected monkeys are heterozygous for a nonsense mutation in exon 6 of the LDLR gene. This mutation changes the sequence of the codon for amino acid 284 (tryptophan) from TGG to TAG, thereby generating a nonsense codon potentially resulting in a truncated 283-amino acid protein, ... . Quantitative analyses of RNA obtained from liver biopsies [of affected monkeys] show that the abundance of the LDLR RNA is also reduced by about 50%."
Takenaka et al. (2023): "A rhesus macaque with the fourth highest plasma cholesterol of 501 breeding macaques was identified 22 years ago. Seven offspring with gene mutations causing hypercholesterolemia were obtained. ... Oligogenic mutations of p. (Cys82Tyr) in LDLR and p. (Val241Ile) in MBTPS2 (S2P) caused hypercholesterolemia exceeding cardiovascular risk levels under a 0.1% CH diet. ... [The authors] identified seven and one rhesus macaques with heterozygous and homozygous p. (Cys82Tyr) mutations in LDLR, respectively. The activity of LDLR was 72% in the heterozygotes and 42% in the homozygote. Of these macaques, two animals were also hemizygous for the p. (Val241Ile) mutation in MBTPS2 [rs30530257]. The mRNA expression level of LDLR was reduced to 80% by this hemizygous mutation."
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|LDLR||low density lipoprotein receptor||Macaca mulatta||19||NC_041772.1 (10851254..10893727)||LDLR||Homologene, Ensembl , NCBI gene|
|MBTPS2||membrane bound transcription factor peptidase, site 2||Macaca mulatta||X||NC_041774.1 (21612978..21658872)||MBTPS2||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1556||Hypercholesterolaemia||LDLR||nonsense (stop-gain)||Naturally occurring variant||19||p.(W284*)||G>A in exon 6 in position 914 of the human cDNA resulting in p.(W284*)||1990||2326270|
|1557||Hypercholesterolaemia||LDLR||missense||Naturally occurring variant||19||c.245G>A||p.(C82Y)||2023||37186395|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2023||Takenaka, A., Suzuki, J., Tanaka, H., Hibino, K., Kamanaka, Y., Nakamura, S., Mitsunaga, F., Kawamoto, Y., Morimoto, M., Aisu, S., Natsume, T. :|
|Hypercholesterolemia induced by spontaneous oligogenic mutations in rhesus macaques (Macaca mulatta). J Med Primatol :, 2023. Pubmed reference: 37186395 . DOI: 10.1111/jmp.12642.|
|2000||Takenaka, A., Matsumoto, Y., Nagaya, A., Watanabe, K., Goto, S., Suryobroto, B., Takenaka, O. :|
|Plasma cholesterol levels in free-ranging macaques compared with captive macaques and humans. Primates 41:299-309, 2000. Pubmed reference: 30545181 . DOI: 10.1007/BF02557599.|
|1990||Hummel, M., Li, Z.G., Pfaffinger, D., Neven, L., Scanu, A.M. :|
|Familial hypercholesterolemia in a rhesus monkey pedigree: molecular basis of low density lipoprotein receptor deficiency. Proc Natl Acad Sci U S A 87:3122-6, 1990. Pubmed reference: 2326270 . DOI: 10.1073/pnas.87.8.3122.|
|1988||Scanu, A.M., Khalil, A., Neven, L., Tidore, M., Dawson, G., Pfaffinger, D., Jackson, E., Carey, K.D., McGill, H.C., Fless, G.M. :|
|Genetically determined hypercholesterolemia in a rhesus monkey family due to a deficiency of the LDL receptor. J Lipid Res 29:1671-81, 1988. Pubmed reference: 3244017 .|
- Created by Imke Tammen2 on 17 May 2023
- Changed by Imke Tammen2 on 17 May 2023