Species Association of Hepatitis B Virus (HBV) in Non-Human Apes; Evidence for Recombination between Gorilla and Chimpanzee Variants

Hepatitis B virus (HBV) infections are widely distributed in humans, infecting approximately one third of the world's population. HBV variants have also been detected and genetically characterised from Old World apes; Gorilla gorilla (gorilla), Pan troglodytes (chimpanzee), Pongo pygmaeus (orang-utan), Nomascus nastusus and Hylobates pileatus (gibbons) and from the New World monkey, Lagothrix lagotricha (woolly monkey). To investigate species-specificity and potential for cross species transmission of HBV between sympatric species of apes (such as gorillas and chimpanzees in Central Africa) or between humans and chimpanzees or gorillas, variants of HBV infecting captive wild-born non-human primates were genetically characterised. 9 of 62 chimpanzees (11.3%) and two from 11 gorillas (18%) were HBV-infected (15% combined frequency), while other Old world monkey species were negative. Complete genome sequences were obtained from six of the infected chimpanzee and both gorillas; those from P. t .ellioti grouped with previously characterised variants from this subspecies. However, variants recovered from P. t. troglodytes HBV variants also grouped within this clade, indicative of transmission between sub-species, forming a paraphyletic clade. The two gorilla viruses were phylogenetically distinct from chimpanzee and human variants although one showed evidence for a recombination event with a P.t.e.-derived HBV variant in the partial X and core gene region. Both of these observations provide evidence for circulation of HBV between different species and sub-species of non-human primates, a conclusion that differs from the hypothesis if of strict host specificity of HBV genotypes

The time scale of recombination rate evolution in great apes

We present three linkage-disequilibrium (LD)-based recombination maps generated using whole-genome sequence data from 10 Nigerian chimpanzees, 13 bonobos, and 15 western gorillas, collected as part of the Great Ape Genome Project (Prado-Martinez J, et al. 2013. Great ape genetic diversity and population history. Nature 499:471-475). We also identified species-specific recombination hotspots in each group using a modified LDhot framework, which greatly improves statistical power to detect hotspots at varying strengths. We show that fewer hotspots are shared among chimpanzee subspecies than within human populations, further narrowing the time scale of complete hotspot turnover. Further, using species-specific PRDM9 sequences to predict potential binding sites (PBS), we show higher predicted PRDM9 binding in recombination hotspots as compared to matched cold spot regions in multiple great ape species, including at least one chimpanzee subspecies. We found that correlations between broad-scale recombination rates decline more rapidly than nucleotide divergence between species. We also compared the skew of recombination rates at centromeres and telomeres between species and show a skew from chromosome means extending as far as 10-15Mb from chromosome ends. Further, we examined broad-scale recombination rate changes near a translocation in gorillas and found minimal differences as compared to other great ape species perhaps because the coordinates relative to the chromosome ends were unaffected. Finally, on the basis of multiple linear regression analysis, we found that various correlates of recombination rate persist throughout the African great apes including repeats, diversity, and divergence. Our study is the first to analyze within- And between-species genome-wide recombination rate variation in several close relatives

Effectiveness of non-mydriatic ultra-widefield retinal imaging to screen for diabetic eye disease: a randomized controlled trial (Clearsight)

   Objective Suboptimal diabetic eye disease screening is a major cause of preventable vision loss. Screening barriers include mydriasis and need for dedicated screening appointments. The Clearsight trial assessed whether non-mydriatic ultra-widefield (NM UWF) screening on the day of a diabetes clinic visit improved detection of clinically important eye disease vs usual screening. Research Design and Methods  This single-center, randomized, parallel-group controlled trial was conducted at St. Joseph’s Health Care, London, Canada. Adults with diabetes due for screening were randomized to same-day On-Site Screening (NM UWF imaging) on the day of a scheduled diabetes clinic visit or Usual Screening (encouraged to arrange optometrist screening). The primary outcome was detection of actionable eye disease (AED) defined as need for ophthalmology referral or increased ocular surveillance. The primary analysis (modified intention-to-screen) compared the proportions of AED between groups within one year of enrollment.  Results  Of 740 participants randomized between March 7, 2016 and April 17, 2019, 335 On-Site Screening and 323 Usual Screening participants met criteria for the primary analysis. More AED was detected in the On-Site Screening than Usual Screening groups (50/335 [14.9%] vs 22/323 [6.8%]; adjusted odds ratio 2.51 [95% CI 1.49–4.36]). The number-needed-to-screen by On-Site Screening to detect one additional patient with AED was 13 [95% CI 8–29]. Conclusions  Same-day On-Site Screening by NM UWF imaging increased detection of clinically important diabetic eye disease vs Usual Screening. Integration of NM UWF imaging into routine diabetes clinic visits improved screening adherence and has the potential to prevent vision loss.</p