Whole genomes reveal multiple candidate genes and pathways involved in the immune response of dolphins to a highly infectious virus

2021 ◽  
Author(s):  
Kimberley C. Batley ◽  
Jonathan Sandoval‐Castillo ◽  
Catherine Kemper ◽  
Nikki Zanardo ◽  
Ikuko Tomo ◽  
...  
Author(s):  
Kimberley Batley ◽  
Jonathan Sandoval-Castillo ◽  
Catherine Kemper ◽  
Nikki Zanardo ◽  
Ikuko Tomo ◽  
...  

2021 ◽  
pp. 8-15
Author(s):  
Prabir Chakravarty Ph.D

COVID-19 is fast spreading around the globe in a highly contagious manner. Until date there are no therapeutic agents/vaccines developed which could control this highly infectious virus from spreading among human population. During early stage of COVID-19, stringent Lockdown was implemented throughout India on 25 March, 2020. Our earlier findings reflected that early introduction of complete Lockdown significantly controlled the spread of COVID-19 in the population immediately after Lockdown. It was hypothesized that immune response was responsible for the control of the spread of COVID-19. To further evaluate the role of immune response/passive vaccination, data from COVID-19 positive/recovered individuals in eight states were assessed for the month of December, 2020. The results from our study reflect that in all the eight states, there was marked decrease in the number of confirmed COVID-19 cases after Lockdown, with one region recording no COVID-19 cases. All the states studied had very low number of active cases; the minimum number being two even after such a long period from the start of this disease. A negative correlation between number of recovered individuals and number of active cases of COVID-19 was noted. Here we hypothesize that passive immunization may have played a significant role in controlling SARS-CoV-2. It could be inferred from this study that implementation of prolonged Lockdown was able attenuate the virus and create an environment for the development of passive immunity in the section of population studied.


PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0171828 ◽  
Author(s):  
Md. Aminul Islam ◽  
Christine Große-Brinkhaus ◽  
Maren Julia Pröll ◽  
Muhammad Jasim Uddin ◽  
Sharmin Aqter Rony ◽  
...  

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Aleeza C. Gerstein ◽  
Katrina M. Jackson ◽  
Tami R. McDonald ◽  
Yina Wang ◽  
Benjamin D. Lueck ◽  
...  

ABSTRACT Patient outcomes during infection are due to a complex interplay between the quality of medical care, host immunity factors, and the infecting pathogen’s characteristics. To probe the influence of pathogen genotype on human survival, immune response, and other parameters of disease, we examined Cryptococcus neoformans isolates collected during the Cryptococcal Optimal Antiretroviral Therapy (ART) Timing (COAT) Trial in Uganda. We measured human participants’ survival, meningitis disease parameters, immunologic phenotypes, and pathogen in vitro growth characteristics. We compared those clinical data to whole-genome sequences from 38 C. neoformans isolates of the most frequently observed sequence type (ST), ST93, in our Ugandan participant population and to sequences from an additional 18 strains of 9 other sequence types representing the known genetic diversity within the Ugandan Cryptococcus clinical isolates. We focused our analyses on 652 polymorphisms that were variable among the ST93 genomes, were not in centromeres or extreme telomeres, and were predicted to have a fitness effect. Logistic regression and principal component analysis identified 40 candidate Cryptococcus genes and 3 hypothetical RNAs associated with human survival, immunologic response, or clinical parameters. We infected mice with 17 available KN99α gene deletion strains for these candidate genes and found that 35% (6/17) directly influenced murine survival. Four of the six gene deletions that impacted murine survival were novel. Such bedside-to-bench translational research identifies important candidate genes for future studies on virulence-associated traits in human Cryptococcus infections. IMPORTANCE Even with the best available care, mortality rates in cryptococcal meningitis range from 20% to 60%. Disease is often due to infection by the fungus Cryptococcus neoformans and involves a complex interaction between the human host and the fungal pathogen. Although previous studies have suggested genetic differences in the pathogen impact human disease, it has proven quite difficult to identify the specific C. neoformans genes that impact the outcome of the human infection. Here, we take advantage of a Ugandan patient cohort infected with closely related C. neoformans strains to examine the role of pathogen genetic variants on several human disease characteristics. Using a pathogen whole-genome sequencing approach, we showed that 40 C. neoformans genes are associated with human disease. Surprisingly, many of these genes are specific to Cryptococcus and have unknown functions. We also show deletion of some of these genes alters disease in a mouse model of infection, confirming their role in disease. These findings are particularly important because they are the first to identify C. neoformans genes associated with human cryptococcal meningitis and lay the foundation for future studies that may lead to new treatment strategies aimed at reducing patient mortality.


BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Sèyi Fridaïus Ulrich Vanvanhossou ◽  
Carsten Scheper ◽  
Luc Hippolyte Dossa ◽  
Tong Yin ◽  
Kerstin Brügemann ◽  
...  

Abstract Background Specific adaptive features including disease resistance and growth abilities in harsh environments are attributed to indigenous cattle breeds of Benin, but these breeds are endangered due to crossbreeding. So far, there is a lack of systematic trait recording, being the basis for breed characterizations, and for structured breeding program designs aiming on conservation. Bridging this gap, own phenotyping for morphological traits considered measurements for height at withers (HAW), sacrum height (SH), heart girth (HG), hip width (HW), body length (BL) and ear length (EL), including 449 cattle from the four indigenous Benin breeds Lagune, Somba, Borgou and Pabli. In order to utilize recent genomic tools for breed characterizations and genetic evaluations, phenotypes for novel traits were merged with high-density SNP marker data. Multi-breed genetic parameter estimations and genome-wide association studies (GWAS) for the six morphometric traits were carried out. Continuatively, we aimed on inferring genomic regions and functional loci potentially associated with conformation, carcass and adaptive traits. Results SNP-based heritability estimates for the morphometric traits ranged between 0.46 ± 0.14 (HG) and 0.74 ± 0.13 (HW). Phenotypic and genetic correlations ranged from 0.25 ± 0.05 (HW-BL) to 0.89 ± 0.01 (HAW-SH), and from 0.14 ± 0.10 (HW-BL) to 0.85 ± 0.02 (HAW-SH), respectively. Three genome-wide and 25 chromosome-wide significant SNP positioned on different chromosomes were detected, located in very close chromosomal distance (±25 kb) to 15 genes (or located within the genes). The genes PIK3R6 and PIK3R1 showed direct functional associations with height and body size. We inferred the potential candidate genes VEPH1, CNTNAP5, GYPC for conformation, growth and carcass traits including body weight and body fat deposition. According to their functional annotations, detected potential candidate genes were associated with stress or immune response (genes PTAFR, PBRM1, ADAMTS12) and with feed efficiency (genes MEGF11 SLC16A4, CCDC117). Conclusions Accurate measurements contributed to large SNP heritabilities for some morphological traits, even for a small mixed-breed sample size. Multi-breed GWAS detected different loci associated with conformation or carcass traits. The identified potential candidate genes for immune response or feed efficiency indicators reflect the evolutionary development and adaptability features of the breeds.


2019 ◽  
Author(s):  
Aleeza C. Gerstein ◽  
Katrina M. Jackson ◽  
Tami R. McDonald ◽  
Yina Wang ◽  
Benjamin D. Lueck ◽  
...  

AbstractPatient outcomes during infection are due to a complex interplay between the quality of medical care, host immunity factors, and the infecting pathogen’s characteristics. To probe the influence of pathogen genotype on human immune response and disease, we examinedCryptococcus neoformansisolates collected during the Cryptococcal Optimal ART Timing (COAT) trial in Uganda. We measured human participants’ immunologic phenotypes, meningitis disease parameters, and survival. We compared this clinical data to whole genome sequences from 38C. neoformansisolates of the most frequently observed sequence type (ST) ST93 in our Ugandan participant population, and an additional 18 strains from 9 other sequence types representing the known genetic diversity within the UgandanCryptococcusclinical isolates. We focused our analyses on 652 polymorphisms that: were variable among the ST93 genomes, were not in centromeres or extreme telomeres, and were predicted to have a fitness effect. Logistic regression and principal component analyses identified 40 candidateCryptococcusgenes and 3 hypothetical RNAs associated with human immunologic response or clinical parameters. We infected mice with 17 available KN99α gene deletion strains for these candidate genes and found that 35% (6/17) directly influenced murine survival. Four of the six gene deletions that impacted murine survival were novel. Such bedside-to-bench translational research provides important candidate genes for future studies on virulence-associated traits in humanCryptococcusinfections.Author SummaryEven with the best available care, mortality rates in cryptococcal meningitis range from 20-60%. Disease is often due to infection by the fungus Cryptococcus neoformans and involves a complex interaction between the human host and the fungal pathogen. Although previous studies have suggested genetic differences in the pathogen impact human disease, it has proven quite difficult to identify the specific C. neoformans genes that impact the outcome of the human infection. Here, we take advantage of a Ugandan patient cohort infected with closely related C. neoformans strains to examine to role of pathogen genetic variants on several human disease characteristics. Using a pathogen whole genome sequencing approach, we showed that 40 C. neoformans genes are associated with human disease. Surprisingly, many of these genes are specific to Cryptococcus and have unknown functions. We also show deletion of these genes alters disease in a mouse model of infection, confirming their role in disease. These findings are particularly important because they are the first to identify C. neoformans genes associated with human cryptococcal meningitis and lay the foundation for future studies that may lead to new treatment strategies aimed at reducing patient mortality.


Genome ◽  
2019 ◽  
Vol 62 (4) ◽  
pp. 279-285 ◽  
Author(s):  
Hojjat Asadollahpour Nanaei ◽  
Ahmad Ayatollahi Mehrgardi ◽  
Ali Esmailizadeh

Equine athletes have a genetic heritage that has been evolved for millions of years, which provides an opportunity to study the genetics of locomotion pattern and performance in mammals. The Hanoverian, a breed originating in Germany, is arguably among the most athletic of horse breeds, as well as possessing a balanced character and beautiful appearance. Here, we compared the whole genomes of Hanoverian with three other horse breeds (Akhal-Teke, Franches-Montagnes, and Standardbred), using the fixation index (Fst) and cross-population composite likelihood ratio (XP-CLR) methods for testing the multi-locus allele frequency differentiation between populations. We identified 299 and 485 positively selected genes using the Fst and XP-CLR methods, respectively. Further functional analyses showed that the ACTA1 gene is potentially involved in athletic performance in the Hanoverian breed, consistent with its role observed in human population. In addition, three other loci on chromosomes 1 and 20 were identified to be potentially involved in equine physical performance. The selected candidate genes identified in this study may be useful in current breeding efforts to develop improved breeds in regard to athletic performance.


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