* Whole Genome Sequence Data From Captive Baboons Implicate RBFOX1 in Epileptic Seizure Risk.
- In this study, we investigate the genetic determinants that underlie epilepsy in a captive baboon pedigree and evaluate the potential suitability of this non-human primate model for understanding the genetic etiology of human epilepsy. Archived whole-genome sequence data were analyzed using both a candidate gene approach that targeted variants in baboon homologs of 19 genes (n = 20,881 SNPs) previously implicated in genetic generalized epilepsy (GGE) and a more agnostic approach that examined protein-altering mutations genome-wide as assessed by snpEff (n = 36,169). Measured genotype association tests for baboon cases of epileptic seizure were performed using SOLAR, as well as gene set enrichment analyses (GSEA) and protein-protein interaction (PPI) network construction of top association hits genome-wide (p < 0.01; n = 441 genes). The maximum likelihood estimate of heritability for epileptic seizure in the pedigreed baboon sample is 0.76 (SE = 0.77; p = 0.07). Among candidate genes for GGE, a significant association was detected for an intronic SNP in RBFOX1 (p = 5.92 × 10-6; adjusted p = 0.016). For protein-altering variants, no genome-wide significant results were observed for epilepsy status. However, GSEA revealed significant positive enrichment for genes involved in the extracellular matrix structure (ECM; FDR = 0.0072) and collagen formation (FDR = 0.017), which was reflected in a major PPI network cluster. This preliminary study highlights the potential role of RBFOX1 in the epileptic baboon, a protein involved in transcriptomic regulation of multiple epilepsy candidate genes in humans and itself previously implicated in human epilepsy, both focal and generalized. Moreover, protein-damaging variants from across the genome exhibit a pattern of association that links collagen-containing ECM to epilepsy risk. These findings suggest a shared genetic etiology between baboon and human forms of GGE and lay the foundation for follow-up research.
Overview of verb observe
The verb observe has 9 senses (first 8 from tagged texts)
1. (39) detect, observe, find, discover, notice -- (discover or determine the existence, presence,
or fact of; "She detected high levels of lead in her drinking water"; "We found traces of lead in
the paint")
2. (17) note, observe, mention, remark -- (make mention of; "She observed that his presentation took
up too much time"; "They noted that it was a fine day to go sailing")
3. (12) note, take note, observe -- (observe with care or pay close attention to; "Take note of this
chemical reaction")
4. (10) observe -- (watch attentively; "Please observe the reaction of these two chemicals")
5. (4) respect, honor, honour, abide by, observe -- (show respect towards; "honor your parents!")
6. (3) observe, celebrate, keep -- (behave as expected during of holidays or rites; "Keep the
commandments"; "celebrate Christmas"; "Observe Yom Kippur")
7. (2) watch, observe, follow, watch over, keep an eye on -- (follow with the eyes or the mind;
"Keep an eye on the baby, please!"; "The world is watching Sarajevo"; "She followed the men with the
binoculars")
8. (1) observe, keep, maintain -- (stick to correctly or closely; "The pianist kept time with the
metronome"; "keep count"; "I cannot keep track of all my employees")
9. observe, keep -- (conform one's action or practice to; "keep appointments"; "she never keeps her
promises"; "We kept to the original conditions of the contract")
Overview of adj observed
The adj observed has 1 sense (first 1 from tagged texts)
1. (7) ascertained, discovered, observed -- (discovered or determined by scientific observation;
"variation in the ascertained flux depends on a number of factors"; "the discovered behavior norms";
"discovered differences in achievement"; "no explanation for the observed phenomena")
--- WordNet end ---