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Abstract Background Non-inferiority trials are recommended by the World Health Organization (WHO) to demonstrate that health products show comparable efficacy to that of existing standard of care. As part of the WHO Global Malaria Programme (GMP) process of assessment of malaria vector control products, a second-in-class insecticide-treated net (ITN) must be shown to be non-inferior to a first-in-class product based on mosquito mortality. The public health impact of the first-in-class pyrethroid-piperonyl butoxide (PBO) ITN, Olyset® Plus, has been demonstrated in epidemiological trials in areas with insecticide-resistant mosquitoes, but there is a need to determine the efficacy of other pyrethroid-PBO nets to ensure timely market availability of nets in order to increase access to ITNs. The non-inferiority of a deltamethrin-PBO ITN Yorkool® G3 was evaluated entomologically against Olyset® Plus in experimental huts in Tanzania, following WHO guidelines for non-inferiority trials. Methods The trial of the two pyrethroid-PBO ITNs was conducted in experimental huts in Lupiro, Tanzania, using a randomized 7 × 7 Latin square block design. The study ran for 49 nights in 14 huts assessing the mosquito mortality and blood-feeding of wild, free-flying, pyrethroid-resistant Anopheles arabiensis. Using the non-inferiority approach, the comparative efficacy (primary endpoint was mosquito mortality at 24 h and secondary endpoint was blood-feeding) of unwashed and 20 times field-washed pyrethroid-PBO Yorkool® G3 ITNs, were compared with the first-in-class product Olyset® Plus and against a pyrethroid-only ITN, PermaNet® 2.0 ITNs, as a standard comparator. Results The experimental hut trial demonstrated non-inferiority and superiority of Yorkool® G3 to Olyset® Plus based on mosquito mortality [51% vs. 39%, OR 1.68 (95% CI 1.50–1.88)], given that lower 95% CI exceeded 0.74 (delta of 39%) and the margin of no difference (1). Blood-feeding inhibition was high for all treated ITNs (> 90%) and Yorkool® G3 was non-inferior to Olyset® Plus [4% vs. 2%, OR 1.81 (95% CI 1.46–2.39)], given that upper 95% CI was less than 4.85 (delta of 4%). The pyrethroid-PBO ITNs were superior to the pyrethroid-only net, PermaNet® 2.0, as determined by both the proportion of mortality and blood-feeding of mosquitoes (p-value

Salinity poses a significant threat to the floral plants. Melatonin has emerged as a potential phytohormone to cope with the adverse effects of salinity on plants due to its multifaceted roles in regulating abiotic stresses. The current study aimed to investigate the impact of melatonin on pansy by modifications in physiological indices under salinity stress. Pansy plants were subjected to salinity stress (0, 50, and 100 mM NaCl) and melatonin (control, 50, and 100 µM). Salinity-induced oxidative stress was apparent through enhanced generation of toxic substances. However, melatonin supplementation improved chlorophyll ‘a’, chlorophyll ‘b’, total chlorophyll, glycine betaine (GB), superoxidase dismutase (SOD), peroxidase (POD), catalases (CAT), and glutathione-reductase (GR), thus promoting improved growth under salinity. The activation of plant defense system and regulation of signaling molecules is indication of lessening of toxic substances within the plant cells. Current findings revealed that supplementation of melatonin enhanced pansy tolerance against salinity stress.

Abstract Background Increasing metabolic resistance in malaria vector mosquitoes resulted in the development of insecticide-treated nets (ITNs) with active ingredients (AI) that target them. Bioassays that accurately measure the mortality induced by these AIs on ITNs are needed. Mosquito metabolic enzyme expression follows a circadian rhythm. Thus, this study assessed (i) influence of the time of day of mosquito exposure and (ii) timing of assessment of mortality post exposure (24 and 72 h) to ITNs against vectors that are susceptible to pyrethroids and those with metabolic and knockdown resistance mechanisms. Methods Two cone bioassay experiments were conducted following World Health Organization (WHO) guidelines. Firstly, on ITNs incorporated with 2 g AI/kg of deltamethrin (DM) alone, or combined with 8 g AI/kg piperonyl butoxide (PBO) synergist, during the day (9:00–14:00 h) and repeated in the evening (18:00–20:00 h). This was followed by a confirmatory experiment during the afternoon (12:00–14:00 h) and repeated in the night (22:00–24:00 h) using mosquitoes unexposed or pre-exposed to PBO for 1 h before exposure to DM ITNs. Each net piece was tested with a minimum of eight cones per time (N = 24). The outcome was mortality after 24 h (M24) or 72 h (M72) of holding. Results The cone bioassays performed using metabolic resistant mosquitoes during the evening showed significantly lower M24 than those performed in the day for DM: odds ratio (OR) 0.14 [95% confidence interval (CI) 0.06–0.30, p

The first record in Ukraine of Arrhenia chlorocyanea (Hygrophoraceae) is reported. The species is rather rare, or mostly overlooked, in Europe. A complete description of the fruit bodies and details of their microscopic structure is provided. In addition, information on the habitats and worldwide distribution of the species is presented. The article is illustrated with original photos and drawings of the fungus.

The article covers the study of the effect of β-lactoglobulin gene polymorphism on daity productivity, qualitative composition of milk and lactation activity of Holstein cows. The work was carried out on 146 animals in the Lenin Breeding Farm Integrated Agricultural Production Center (IAPC) of the Republic of Tatarstan. DNA genotyping by the locus of the Bos taurus BLG-Hae III gene was performed by PCR-RFLP. As a result of genetic typing of cattle, 2 alleles (A – 0.651 and B – 0.349) and 3 genotypes (AA – 41.1, AB – 47.9 and BB – 11.0 %) were identified. The chi-square criterion is below the critical value (5.99; p < 0.05) and testifies that the Hardy-Weinberg genetic equilibrium is not disturbed in the population. The evaluation of dairy productivity traits showed that cows with the AB genotype have the highest milk yield and high-quality milk. The heifers with the AB genotype are characterized by the best lactation curve throughout lactation. The difference in the amount of milk received between cows with the AB genotype and animals with the AA and BB genotypes is 71.6 kg (or 9.3 %) and 95.7 kg (or 16.9 %), respectively. Cows with low milk yields (genotype AA) had the lowest lactation decline (4.34) and greater stability (99.9).

Gallium-containing chlorite, mica, and magnetite (up to 14, 13, and 5-7 wt % of Ga) along with Ga hydroxides (oxyhydroxides?) were found for the first time in massive sulfide deposit in the Urals. The minerals identified within the cement of chalcopyrite-sphalerite breccias of the Shemur copper-zinc-massive sulfide deposit (Northern Urals) are associated with Ga-enriched sphalerite, chalcopyrite, and, less commonly, pyrite (33-364, 67-363, and 4-230 g/t, respectively). [ABSTRACT FROM AUTHOR]

This study aimed to determine the effect of hydrogen sulfide on chilling injury (CI) of banana (Musa spp.) during cold storage (7°C). It was observed that hydrogen sulfide application (2 mmol L–1) markedly reduced the CI index and showed significantly higher chlorophyll contents, along with suppressed chlorophyll peroxidase and chlorophyllase enzyme activity. The treated banana fruits exhibited substantially higher peel lightness (L*), along with significantly a lower browning degree and soluble quinone content. The treated bananas had substantially a higher endogenous hydrogen sulfide content and higher activity of its biosynthesis-associated enzymes such as D-cysteine desulfhydrase (DCD) and L-cysteine desulfhydrase (LCD), along with significantly lower ion leakage, lipid peroxidation, hydrogen peroxide, and superoxide anion concentrations. Hydrogen sulfide-treated banana fruits showed an increased proline content and proline metabolism-associated enzymes including ornithine aminotransferase (OAT), Δ1-pyrroline-5-carboxylate synthetase (P5CS), and proline dehydrogenase (PDH). In the same way, hydrogen sulfide-fumigated banana fruits accumulated higher endogenous γ-aminobutyric acid (GABA) due to enhanced activity of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T) enzymes. The hydrogen sulfide-treated fruits exhibited higher total phenolics owing to lower polyphenol oxidase (PPO) and peroxidase (POD) activity and stimulated phenylalanine ammonia lyase (PAL). The treated banana exhibited higher ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR), dehydroascorbate reductase (DHAR), monodehydroascorbate reductase (MDHAR), and superoxide dismutase (SOD) activity, along with higher glutathione (GSH) and ascorbic acid (AsA) concentrations and a significantly lower dehydroascorbic acid (DHA) content. In conclusion, hydrogen sulfide treatment could be utilized for CI alleviation of banana fruits during cold storage.

Salt stress negatively affects the growth, development, and yield of horticultural crops. Nitric oxide (NO) is considered a signaling molecule that plays a key role in the plant defense system under salt stress. This study investigated the impact of exogenous application of 0.2 mM of sodium nitroprusside (SNP, an NO donor) on the salt tolerance and physiological and morphological characteristics of lettuce (Lactuca sativa L.) under salt stress (25, 50, 75, and 100 mM). Salt stress caused a marked decrease in growth, yield, carotenoids and photosynthetic pigments in stressed plants as compared to control ones. Results showed that salt stress significantly affected the oxidative compounds (superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX)) and non-oxidative compounds (ascorbic acid, total phenols, malondialdehyde (MDA), proline, and H2O2) in lettuce. Moreover, salt stress decreased nitrogen (N), phosphorous (P), and potassium ions (K+) while increasing Na ions (Na+) in the leaves of lettuce under salt stress. The exogenous application of NO increased ascorbic acid, total phenols, antioxidant enzymes (SOD, POD, CAT, and APX) and MDA content in the leaves of lettuce under salt stress. In addition, the exogenous application of NO decreased H2O2 content in plants under salt stress. Moreover, the exogenous application of NO increased leaf N in control, and leaf P and leaf and root K+ content in all treatments while decreasing leaf Na+ in salt-stressed lettuce plants. These results provide evidence that the exogenous application of NO on lettuce helps mitigate salt stress effects.

The study examined the polymorphism of the glutathione peroxidase-1 gene (GPX-1, g. 189 T/C) effect on the GPx enzyme activity and biochemical parameters in the blood serum of Holstein cows of indigenous and foreign selection. The work was carried out in the Lenin Breeding Farm Integrated Agricultural Production Center (IAPC) and the Mukhametshin Z.Z. Peasant Farm Enterprise (PFE) of the Republic of Tatarstan. DNA genotyping by the locus of the Bos taurus GPX-1-Bsc4 I gene was performed by PCR-RFLP. As a result of genetic typing of cattle, 2 alleles (C and T) and 3 genotypes (CC, TC and TT) were identified. The classification carried out by PIC values in two populations of Holstein cattle showed that there is a moderate polymorphism of the GPX-1 gene. A negative inbreeding coefficient (F) indicates excessive outbreeding in both populations. In both populations, the numerical advantage of heterozygous genotype TC cows is 60.1 and 56.7 % of the total livestock. Indigenous breeding cows, compared with imported cattle had higher: GPx activity, AST, ALT, cholesterol level, total protein and albumin fraction. Analysis of the association between the GPX-1 gene polymorphism and the GPx enzyme level indicates that the activity of this enzyme varies depending on the genotype, and there is also a variation in the biochemical parameters of the Holstein cattle blood serum.

Tomato is considered as a valuable vegetable crop all over the world. It prefers loose, well drained loamy soils rich in organic matter. In Pakistan, mostly soils are calcareous in nature. In calcareous soils, the production of tomato crop is low because of zinc deficiency. Therefore, current study was aimed to examine the potential of foliar application of zinc oxide in tomato cultivar Tiny Tim Cherry in calcareous soil conditions. In the current study, all the studied traits i.e. plant height, stem diameter, number of branches per plant, number of leaves, number of flowers per plant, fruit weight and yield per plant were significantly higher after foliar application of zinc oxide (30 ppm) and significantly lower in controlled treatment as compared to other treatments of zinc oxide. The maximum total soluble solids (TSS), chlorophyll A, chlorophyll B, vitamin C, flavonoids, carotenoids and phenolics were recorded in plants treated with 30 ppm of zinc oxide as compared to other treatments. However, the highest acidity was calculated in 10 ppm, while the lowest acidity was measured in 0 ppm (control). Conclusively, foliar application of Zn has potential to increase the nutritional components of tomato fruits.

Tomato is an important vegetable that is highly sensitive to drought (DR) stress which impairs the development of tomato seedlings. Recently, melatonin (ME) has emerged as a nontoxic, regulatory biomolecule that regulates plant growth and enhances the DR tolerance mechanism in plants. The present study was conducted to examine the defensive role of ME in photosynthesis, root architecture, and the antioxidant enzymes’ activities of tomato seedlings subjected to DR stress. Our results indicated that DR stress strongly suppressed growth and biomass production, inhibited photosynthesis, negatively affected root morphology, and reduced photosynthetic pigments in tomato seedlings. Per contra, soluble sugars, proline, and ROS (reactive oxygen species) were suggested to be improved in seedlings under DR stress. Conversely, ME (100 µM) pretreatment improved the detrimental-effect of DR by restoring chlorophyll content, root architecture, gas exchange parameters and plant growth attributes compared with DR-group only. Moreover, ME supplementation also mitigated the antioxidant enzymes [APX (ascorbate peroxidase), CAT (catalase), DHAR (dehydroascorbate reductase), GST (glutathione S-transferase), GR (glutathione reductase), MDHAR (monodehydroascorbate reductase), POD (peroxidase), and SOD (superoxide dismutase)], non-enzymatic antioxidant [AsA (ascorbate), DHA (dehydroascorbic acid), GSH (glutathione), and GSSG, (oxidized glutathione)] activities, reduced oxidative damage [EL (electrolyte leakage), H2O2 (hydrogen peroxide), MDA (malondialdehyde), and O2•− (superoxide ion)] and osmoregulation (soluble sugars and proline) of tomato seedlings, by regulating gene expression for SOD, CAT, APX, GR, POD, GST, DHAR, and MDHAR. These findings determine that ME pretreatment could efficiently improve the seedlings growth, root characteristics, leaf photosynthesis and antioxidant machinery under DR stress and thereby increasing the seedlings’ adaptability to DR stress.

The aim of the work was to study serum biochemical parameters and qualitative composition of milk of cows with various genotypes of the LEP gene. The research was conducted in 148 Holstein cow-heifers of Integrated Agricultural Production Centre “Stud farm named after Lenin” of the Atninsky district of the Republic of Tatarstan. Cattle genotyping was conducted by the AC-PCR method at the laboratory of the Department of Agrobiological Research of Tatar Research Institute of Agriculture of FRC KazanSC of RAS. The findings of allele and genotype calling of the LEP gene showed that the population under study is polymorphic and differs in genetic biodiversity. The study of serum biochemical parameters of experimental animals testified that the level of triglycerides, cholesterol and lipase is meaningfully lower in the blood of animals with the TT genotype. This indicates the rate of lipid metabolism in their body. During the analysis of milk productivity and parameters of the qualitative composition of milk, it was found that cow-heifers with the TT genotype of the LEP gene were superior to animals with other LEP gene genotypes in terms of milk yield for standard lactation (305 days), fat mass fraction, milk fat yield, milk fat and milk protein yield in total. Thus, it may be concluded that the TT genotype of the LEP gene has a positive effect on the economically important characters of cattle, which can be used in breeding in the future.

The aim of the work was to study the traits of dairy productivity of Holstein heifers with different genotypes of the paraoxonase-1 (PON1) gene. The research was conducted in 148 animals of Integrated Agricultural Production Centre “Stud farm named after Lenin” of Atninsky district of the Republic of Tatarstan. Genotyping of cattle was carried out by the PCR-RFLP method at the laboratory of the Department of Agrobiological Research of Tatar Scientific Research Institute of Agriculture, FRC Kazan Scientific Center, Russian Academy of Sciences. The results of allele and genotype calling of the PON1 gene showed that the study population is polymorphic and differs in genetic biodiversity. During the analysis of daity productivity, qualitative composition of milk and lactational activity, it was found that cow-heifers with the GG genotype of the PON1 gene were superior to animals with other genotypes in all the test parameters. Thus, it follows that the GG genotype of the PON1 gene has a positive effect on the economic characters of cattle, which can be used in breeding in the future.

ABSTRACT Bitter gourd is of great importance due to its usage against the treatment of numerous ailments in human beings. A comprehensive survey at four localities of Southern Punjab, Pakistan was carried out to determine the severity of Myrothecium leaf spot. Maximum disease severity was at C1 (Chak 11/NP) and least at C2 (Kot Mehtab). Among isolated species Myrothecium roridum was found more prevalent and pathogenic as compared to M. verrucaria. Antifungal activity using solvent extracts of five medicinal plants (Mangifera indica, Melia azedarach, Nicotiana tabacum, Moringa oleifera and Eucalyptus globosum) were evaluated against isolated species by agar well diffusion method at various concentrations (0.01, 0.10, 1.0 and 10.0 µg / mL). N. tabacum revealed maximum zone size (13.40 mm and 8.28 mm) with ethanol and chloroform solvents respectively followed by M. azedarach (9.00mm and 6.48mm). However, least inhibition was observed with ethanol and chloroform extracts of E. globosum (6.04mm and 3.88mm zone size respectively). Ethanol extracts showed highest activity when compared to chloroform extracts. Qualitative phytochemical analysis showed that all the selected plants are rich in chemical compounds such as alkaloids, terpenoids, flavonoids and phenols whereas Saponins was only present in N. tabacum while absent in rest of the extracts.

The research presents the findings of DNA testing of allelic polymorphism by the PCR-RFLP method of the SCD1 gene and the relationship of genotypes with the milk fatty acid composition of Holstein cows of Tatarstan population. The research was conducted among 172 Holstein cows at the Integrated Agricultural Production Centre “Stud farm named after Lenin” in Atninsky district of the Republic of Tatarstan in 2017–2018. All genotypes of the SCD1 gene were identified through the research. The milk yield test showed that the maximum content of the mass fraction of fat was in animals with the TT genotype. The significant difference between the content of the mass fraction of fat in milk in individuals by the locus of the SCD1-Fsp4H I gene was: TT to CC – 0.32 % (p < 0.05) and TT to TC – 0.40 % (p < 0.01). The results of chromatography indicate the balance of the milk fatty acid composition of cows with the TT genotype and, as a consequence, its positive effect on the human body. Cows with a homozygous TT genotype are characterized by the optimum ratio of fatty acids in milk fat. The maximum value of the oxygen desaturation index is also observed in animals with the TT genotype by the SCD1 gene.

The research presents the findings of DNA testing of allelic polymorphism by the AC-PCR method of the LEP gene. The research was conducted among 172 Holstein cows at Integrated Agricultural Production Centre “Stud farm named after Lenin” in Atninsky district of the Republic of Tatarstan in 2017–2018. All genotypes of the LEP gene were identified through the research. Associations of the leptin gene polymorphism with dynamics of milk production during three lactations of Holstein cows were established. The best indicators for all three lactations were found in a group of animals with the TT genotype of the LEP gene. These individuals are characterized by increased milk yield, a high yield index, and tend to increase the average daily milk yield during three lactations. These individuals are characterized by increased milk yield, a high milk yield index, and tend to increase the average daily milk yield during three lactations.

The study presents the results obtained in DNA testing of allelic polymorphism by PCR-RFLP based methods for the leptin and stearoyl-coenzyme A desaturase genes and the interaction of their complex genotypes on the milk productivity indicators of Holstein heifers of Tatarstan population. The study was carried out among 471 Holstein cow-heifers by Integrated Agricultural Production Centre “Stud farm named after Lenin” of Atninsky district of the Republic of Tatarstan in 2016–2018. All complex LEP/SCD1 genotypes were identified through the study. The maximum frequency was observed in the combination of heterozygous genotypes LEPTCSCD1TC 149 animals (31.5 %). Milk productivity test, based on the complex genotypes LEP and SCD1, showed that a significantly high level of productivity for 305 days of lactation was 7314.4 kg, and in heifers with a complex genotype LEPTTSCD1CC was minimal (6337.4 kg) in comparison with indicators of milk yield of heifers with other complex genotypes. According to the content of the mass fraction of fat, reliably the best indicators were established in a subpopulation of animals with a complex TT/TC genotype 3.87 %. The content of the mass fraction of protein was maximal for animals with a complex CC/CC genotype.

Air- and sun-dried raisins from Thompson Seedless (TS) grapes were analyzed under GC/MS to evaluate fatty acids (FAs) and their derived volatile compounds, coming from unsaturated fatty acids oxidation. A total of 16 FAs were identified in TS raisins, including 10 saturated fatty acids (SFAs) and 6 unsaturated fatty acids (USFAs). The contents of C18:0, C15:0, and C16:0 among SFAs and C18:3, C18:2 and C18:1 in USFAs were significantly higher. Furthermore, USFAs such as C16:1 and C20:1 were only identified in air-dried raisins. The principal component analysis showed the increased content of FAs and FA-derived compounds were in air-dried and sun-dried raisins, respectively. Among FA-derived compounds, 2-pentyl furan, 3-octen-2-one, 1-hexanol and heptanoic acid were more potent. This study shows that air-drying is more favorable for the production of fatty acids (SFAs and USFAs), whereas sun-drying is more advantageous in terms of fatty acid-derived volatiles.

Purpose: Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12., Methods: We used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids., Results: We found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators' recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment., Conclusion: Our study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity., Competing Interests: Conflict of Interest J.R.L. owns stock in 23andMe and is a paid consultant for Genome International. All other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nicolaides-Baraitser syndrome (NCBRS) is a neurodevelopmental disorder caused by pathogenic sequence variants in SMARCA2 which encodes the catalytic component of the chromatin remodeling BAF complex. Pathogenic variants in genes that encode epigenetic regulators have been associated with genome-wide changes in DNA methylation (DNAm) in affected individuals termed DNAm signatures., Methods: Genome-wide DNAm was assessed in whole-blood samples from the individuals with pathogenic SMARCA2 variants and NCBRS diagnosis (n = 8) compared to neurotypical controls (n = 23) using the Illumina MethylationEPIC array. Differential methylated CpGs between groups (DNAm signature) were identified and used to generate a model enabling classification variants of uncertain significance (VUS; n = 9) in SMARCA2 as "pathogenic" or "benign". A validation cohort of NCBRS cases (n = 8) and controls (n = 96) demonstrated 100% model sensitivity and specificity., Results: We identified a DNAm signature of 429 differentially methylated CpG sites in individuals with NCBRS. The genes to which these CpG sites map are involved in cell differentiation, calcium signaling, and neuronal function consistent with NCBRS pathophysiology. DNAm model classifications of VUS were concordant with the clinical phenotype; those within the SMARCA2 ATPase/helicase domain classified as "pathogenic". A patient with a mild neurodevelopmental NCBRS phenotype and a VUS distal to the ATPase/helicase domain did not score as pathogenic, clustering away from cases and controls. She demonstrated an intermediate DNAm profile consisting of one subset of signature CpGs with methylation levels characteristic of controls and another characteristic of NCBRS cases; each mapped to genes with ontologies consistent with the patient's unique clinical presentation., Conclusions: Here we find that a DNAm signature of SMARCA2 pathogenic variants in NCBRS maps to CpGs relevant to disorder pathophysiology, classifies VUS, and is sensitive to the position of the variant in SMARCA2. The patient with an intermediate model score demonstrating a unique genotype-epigenotype-phenotype correlation underscores the potential utility of this signature as a functionally relevant VUS classification system scalable beyond binary "benign" versus "pathogenic" scoring. This is a novel feature of DNAm signatures that could enable phenotypic predictions from genotype data. Our findings also demonstrate that DNAm signatures can be domain-specific, highlighting the precision with which they can reflect genotypic variation.