Potential damaging mutation in LRP5 from genome sequencing of the first reported chimpanzee with the Chiari malformation

The genus Pan is the closest related to humans (Homo sapiens) and it includes two species: Pan troglodytes (chimpanzees) and Pan paniscus (bonobos). Different characteristics, some of biomedical aspect, separate them from us. For instance, some common human medical conditions are rare in chimpanzees (menopause, Alzheimer disease) although it is unclear to which extent longevity plays an active role in these differences. However, both humans and chimpanzees present similar pathologies, thus, understanding traits in chimpanzees can help unravel the molecular basis of human conditions. Here, we sequenced the genome of Nico, a central chimpanzee diagnosed with a particular biomedical condition, the Chiari malformation. We performed a variant calling analysis comparing his genome to 25 whole genomes from healthy individuals (bonobos and chimpanzees), and after predicting the effects of the genetic variants, we looked for genes within the OMIM database. We found a novel, private, predicted as damaging mutation in Nico in LRP5, a gene related to bone density alteration pathologies, and we suggest a link between this mutation and his Chiari malformation as previously shown in humans. Our results reinforce the idea that a comparison between humans and chimpanzees can be established in this genetic frame of common diseases. M.S.-M. is supported by the Ministerio de Economía y Competitividad, Spain (Maria de Maetzu grant MDM-2014-0370-16-3). M.d.M. is supported by a Formació de personal Investigador fellowship from Generalitat de Catalunya (FI_B01111). J.H.-R. is supported by the Ministerio de Economía y Competitividad, Spain (FPI grant BES-2013-064333). C.F. is supported by La Caixa Foundation. A.N. is funded by MINECO BFU2015-68649-P. T.M.-B. is supported by MINECO BFU2014-55090- P (FEDER), U01 MH106874 grant, Howard Hughes International Early Career, La Caixa Foundation and Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat de Catalunya.