Role of Q675H Mutation in Improving SARS-CoV-2 Spike Interaction with the Furin Binding Pocket

Genotype screening was implemented in Italy and showed a significant prevalence of new SARS-CoV-2 mutants carrying Q675H mutation, near the furin cleavage site of spike protein. Currently, this mutation, which is expressed on different SARS-CoV-2 lineages circulating worldwide, has not been thoughtfully investigated. Therefore, we performed phylogenetic and biocomputational analysis to better understand SARS-CoV-2 Q675H mutants’ evolutionary relationships with other circulating lineages and Q675H function in its molecular context. Our studies reveal that Q675H spike mutation is the result of parallel evolution because it arose independently in separate evolutionary clades. In silico data show that the Q675H mutation gives rise to a hydrogen-bonds network in the spike polar region. This results in an optimized directionality of arginine residues involved in interaction of spike with the furin binding pocket, thus improving proteolytic exposure of the viral protein. Furin was predicted to have a greater affinity for Q675H than Q675 substrate conformations. As a consequence, Q675H mutation could confer a fitness advantage to SARS-CoV-2 by promoting a more efficient viral entry. Interestingly, here we have shown that Q675H spike mutation is documented in all the VOCs. This finding highlights that VOCs are still evolving to enhance viral fitness and to adapt to the human host. At the same time, it may suggest Q675H spike mutation involvement in SARS-CoV-2 evolution.

Genotype screening of Cannabis sativa L. based on the specifics of minor cannabinoids manifestation

Analysis of hemp collection samples based on the content of minor (rare) non-psychotropic cannabinoids, such as cannabichromene (CBC), cannabidivarin (CBDV), and cannabinol (CBN); determination of correlation relationships between them and common compounds; selection of valuable breeding genotypes. Methods. Field, biochemical (gas chromatography of cannabinoid compounds), and statistical (pair, partial, and multiple linear correlations). Results. Quantitative analysis of 210 samp­les of various ecological-geographical and genetic origin (local and wild forms, self-filing lines, hybrids, varieties, synthetic populations, polyploids) with a tetrahydrocannabinol (THC) content of less than 0.08% in dried plants showed the level of manifestation of the trait from its absence within the sensitivity of the gas chromatograph up to 0.6838% CBC, 0.1719% CBC and 0.3274% CBN. In the studied hemp samples, a medium negative relationship was found between the signs of the CBC and cannabidiol (CBD) contents (r = –0.53), a weak negative relationship between CBC and CBDV contents (r = –0.35), medium positive relationships between the signs of CBC and THC contents (r = 0.57) and CBC and CBN contents (r = 0.59). A medium positive correlation (r = 0.57) was found between the signs of CBDV and CBD contents, while CBN had a strong positive relationship with THC (r = 0.82). There is almost no correlation between cannabigerol (CBG) and the minor cannabinoids under study. The biosynthesis of minor cannabinoid compounds is quite complex. Signs manifestation is affected by many genetic and external factors. Partial correlation coefficients (given that one of the three signs is eliminated) and multiple correlation coefficients (given that the relationship of one sign is determined and two other signs are combined) give grounds to state that the gene for CBCA-synthase affects the production of CBD and, in particular THC. Conclusions. The closeness of the linear relationships between minor cannabinoids and common components allows selecting valuable hemp samples with a high content of one or several compounds under the absence or low content of psychotropic THC.

HPV-specific risk assessment of cervical cytological abnormalities

Background Cytology and HPV genotype screening play an important role in cervical cancer detection. Whether multiple HPV genotyping can predict cytological lesions remains to be further studied. Methods Two thousand two hundred twenty-four females were analyzed for cytology and HPV genotypes test. The possibility of predicting cytological lesions by HPV genotypes test was evaluated by multivariate logistic regression and area under the receiver operator characteristic curve (AUC). Result Abnormal cytological results were found in 479 participants. A total of 688 patients were detected with HPV infection, 619 with HR-HPV infection and 112 with LR-HRV infection. HPV-52 was found to be the most common type among these patients, and a relatively higher risk of cervical lesions was found in HPV positive females. HPV-16, 31, 33 and 58 were found to have significantly higher infection rates in patients with HSIL and higher lesions. The prediction model was developed based on age and HPV-specific genotypes, with the AUC of 0.73 for cytological abnormalities and 0.82 for HSIL and higher lesions. Conclusion HPV-16, 31, 33 and 58 infection are significant risk factors for cervical lesions. Combined HPV genotypes test can effectively predict cytological abnormalities.

Identification of β Casein Genotypes in Indian Gir and Crossbred Exotic Cows from Mumbai Dairy Farms

Background: Collective evidence of polymorphic β-casein and associated health problems has led to the concern about milk consumption and cow breeding policies worldwide. This association has also engrossed the interest of dairy scientist and industry in evaluation of β casein genotype distribution. With increasing proportion of exotic and crossbred cows in India it is worth while to screen cattle for A1A2 β casein and enhance indigenous cow breeds. Methods: The present study intended to identify β casein genotypes in pure Indian Gir cows and crossbred Holstein and jersey cows from three local dairy farms. We analysed β casein genotypes by PCR-RFLP method in total 95 cows during the period of 2017-2019. Result: All the indigenous Gir cows had fixed A2 allele whereas crossbred Jersey and Holstein Frisian both had A1A2 as the most common genotype (frequency: 0.473 and 0.6 respectively) followed by A2A2 (Frequency 0.368 and 0.333 respectively) and A1A1 (Frequency 0.158 and 0.066 respectively). The results show that in this study group Gir, a native Indian breed has fixed A2 β casein variant whereas crossbred Jersey and Holstein Frisian have A1A2 as a most common genotype. Screening of cattle for â casein genotypes is vital to monitor the frequency of A1 beta casein in native Indian cow breeds.

Molecular Epidemiology of G6PD Genotypes in Different Ethnic Groups Residing in Saharan and Sahelian Zones of Mauritania

Plasmodium vivax malaria is endemic in Mauritania. Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may develop acute hemolytic anemia when exposed to 8-aminoquinoline antimalarial drugs, which are indispensable for a complete cure. The prevalence of G6PD allelic variants was assessed in different ethno-linguistic groups present in Mauritania. A total of 996 blood samples (447 males and 549 females; 499 white Moors and 497 individuals of black African ancestry) were collected from febrile patients in 6 different study sites: Aleg, Atar, Kiffa, Kobeni, Nouakchott, and Rosso. The presence of the African-type G6PD A- (G202A, A376G, A542T, G680T, and T968C mutations) and the Mediterranean-type G6PD B- (C563T) variants was assessed by PCR followed by restriction fragment length polymorphism and/or DNA sequencing. The prevalence of African-type G6PD A- genotype was 3.6% (36/996), with 6.3% (28/447) of hemizygote (A-) males and 1.5% (8/549) of homozygous (A-A-) females. Forty of 549 (7.3%) women were heterozygous (AA-). The following genotypes were observed among hemizygous men and/or homozygous women: A376G/G202A (22/996; 2.2%), A376G/T968C Betica-Selma (12/996; 1.2%), and A376G/A542T Santamaria (2/996; 0.2%). The Mediterranean-type G6PD B- genotype was not observed. The prevalence rates of G6PD A- genotype in male (10/243; 4.1%) and heterozygous female (6/256; 2.3%) white Moors were lower (p < 0.05) than those of males (18/204; 8.8%) and heterozygous females (34/293; 11.6%) of black African ancestry. There were only a few homozygous women among both white Moors (3/256; 1.2%) and those of black African ancestry (5/293; 1.7%). The prevalence of G6PD deficiency in Mauritania was comparable to that of neighboring countries in the Maghreb. Because of the purportedly close ethnic ties between the Mauritanian white Moors and the peoples in the Maghreb, further investigations on the possible existence of the Mediterranean-type allele are required. Moreover, a surveillance system of G6PD phenotype and/or genotype screening is warranted to establish and monitor a population-based prevalence of G6PD deficiency.

Polly Wants a Genome: The Lack of Genetic Testing for Pet Parrot Species

Parrots are considered the third most popular pet species, after dogs and cats, in the United States of America. Popular birds include budgerigars, lovebirds and cockatiels and are known for their plumage and vocal learning abilities. Plumage colour variation remains the main driving force behind breeder selection. Despite the birds’ popularity, only two molecular genetic tests—bird sexing and pathogen screening—are commercially available to breeders. For a limited number of species, parentage verification tests are available, but are mainly used in conservation and not for breeding purposes. No plumage colour genotyping test is available for any of the species. Due to the fact that there isn’t any commercial plumage genotype screening or parentage verification tests available, breeders mate close relatives to ensure recessive colour alleles are passed to the next generation. This, in turn, leads to inbreeding depression and decreased fertility, lower hatchability and smaller clutch sizes, all important traits in commercial breeding systems. This review highlights the research carried out in the field of pet parrot genomics and points out the areas where future research can make a vital contribution to understanding how parrot breeding can be improved to breed healthy, genetically diverse birds.

Community based screening for sickle haemoglobin among pregnant women in Benue State, Nigeria: I-Care-to-Know, a Healthy Beginning Initiative

Background Haemoglobin genotype screening at prenatal care offers women an opportunity to be aware of their genotype, receive education on sickle cell disease (SCD) and may increase maternal demand for SCD newborn screening. In developed countries, most pregnant women who access prenatal care and deliver at the hospital receive haemoglobin genotype screening. In settings with low prenatal care attendance and low hospital deliveries, community-based screening may provide similar opportunity for pregnant women. We assessed the feasibility and acceptability of integrating haemoglobin genotype screening into an existing community-based HIV program. Methods Onsite community-based integrated testing for HIV, hepatitis B virus and haemoglobin electrophoresis, were conducted for pregnant women and their male partners. Community Health Advisors implementing the NIH and PEPFAR-supported Healthy Beginning Initiative (HBI) program provided education on SCD, collected blood sample for haemoglobin electrophoresis and provided test results to participants enrolled into the HBI program. We concurrently conducted a cross-sectional study using a pretested, semi-structured, interviewer administered questionnaire to collect demographic data and assess awareness of individual haemoglobin “genotype” among HBI pregnant women participants. Results In this study, 99.9% (10,167/10,168) of pregnant women who received education on SCD accepted and completed the survey, had blood drawn for haemoglobin electrophoresis and received their results. A majority of participating pregnant women (97.0%) were not aware of their haemoglobin “genotype”. Among the participants who were incorrect about their haemoglobin “genotype”, 41.1% (23/56) of women who reported their haemoglobin “genotype” as AA were actually AS. The odds of haemoglobin “genotype” awareness was higher among participants who were in younger age group, completed tertiary education, had less number of pregnancies, and attended antenatal care. Overall prevalence of sickle cell trait (AS) was 18.7%. Conclusions It is feasible to integrate haemoglobin “genotype” testing into an existing community-based maternal-child program. Most pregnant women who were unaware of their haemoglobin “genotype” accepted and had haemoglobin genotype testing, and received their test results. Increasing parental awareness of their own haemoglobin “genotype” could increase their likelihood of accepting newborn screening for SCD.

Correlations between FTO Gene Polymorphisms and TSH Level in Uyghur Chinese Patients with Type 2 Diabetes

Objective. The aim of this study was to investigate the correlation between polymorphisms in the FTO gene and TSH level in Uyghur patients with type 2 diabetes in the Xinjiang region. Material and Methods. This cohort was made up of 498 Uyghur patients with type 2 diabetes who underwent genotype screening for rs8050136 and rs9939609 using the Sequenom MassARRAY system. The distribution frequencies of the genotypes and alleles at rs8050136 and rs993960 were compared between two patient groups, those with TSH < 2.5 mU/L and those with TSH ≥ 2.5 mU/L group. We further evaluated the relationships between these different genotypes and FT3, FT4, TSH, FPG, and HbA1c expression. Results. The results suggested the TSH level was 2.281 times higher in rs8050136 CC+CA carriers than in AA genotype ( 95 % CI = 1.024 ~5.080, P = 0.044 ) and was 2.417 times higher in rs9939609 TT+TA carriers than in AA genotype ( 95 % CI = 1.257 ~4.649, P = 0.008 ) after adjusting for age, sex, and BMI under the recessive model. TSH levels were significantly different between T2DM patients with different FTO genotypes, rs8050136 ( P = 0.008 ) and rs9939609 ( P = 0.003 ), with TSH levels in rs8050136 CC genotype carriers showing a significant increase compared to those in the AA genotype carriers ( P = 0.005 ). Additionally, rs9939609 TT and TA genotype carriers had a significant increase in the TSH level when compared to AA genotype carriers ( P = 0.001 and P = 0.031 , respectively). The TSH level was also significantly different in these male patients with different genotypes of rs8050136 ( P = 0.026 ) and rs9939609 ( P = 0.019 ). And TSH levels in rs8050136 CC genotype male carriers showing a significant increase compared to those in the AA genotype carriers ( P = 0.013 ) and rs9939609 TT genotype male carriers had a significant increase in TSH level when compared to AA genotype carriers ( P = 0.004 ). Conclusion. The polymorphisms at rs8050136 and rs9939609 are associated with changes in the TSH level with rs8050136 CC and rs9939609 TT genotypes identified as potential risk factors for increased TSH levels in these male patients.