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

Abstract

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.

Humans and Chimpanzees Display Opposite Patterns of Diversity in Arylamine N-Acetyltransferase Genes

“…As foreseen by Olson and Varki (2003), analyzing genetic and genomic diversity in the great apes is also providing novel insights of medical interest ( e.g. , (Enard et al 2002; Bergfeld et al 2017; Solis-Moruno et al 2017). Indeed, physiological differences between species, whether they emerged through demographic processes or as adaptive responses might offer insights into present-day questions regarding human health and disease (Olson and Varki 2003; O’Bleness et al 2012).…”

A combined RNA-seq and whole genome sequencing approach for identification of non-coding pathogenic variants in single families

“…Interestingly, vision phenotypes such as photophobia, vision loss and nystagmus have been reported as accompanying symptoms in some forms of Chiari malformations 57–60 . Unfortunately, despite evidence that Chiari malformations have a hereditable component 61–63 , the genes involved are not yet well defined 59, 64, 65 . For that reason we could not rule out the possibility that the vision phenotypes and Chiari malformations share a common genetic causality.…”

A combined RNA-seq and whole genome sequencing approach for identification of non-coding pathogenic variants in single families

“…Interestingly, vision phenotypes such as photophobia, vision loss and nystagmus have been reported as accompanying symptoms in some forms of Chiari malformations [57][58][59][60] . Unfortunately, despite evidence that Chiari malformations have a hereditable component [61][62][63] , the genes involved are not yet well defined 59,64,65 . For that reason we could not rule out the possibility that the vision phenotypes and Chiari malformations share a common genetic causality.…”