Polygenic Complex Research Articles

Unraveling schizophrenia's genetic complexity through advanced causal inference and chromatin 3D conformation

Schizophrenia is a polygenic complex disease with a heritability as high as 80 %, yet the mechanism of polygenic interaction in its pathogenesis remains unclear. Studying the interaction and regulation of schizophrenia susceptibility genes is crucial for unraveling the pathogenesis of schizophrenia and developing antipsychotic drugs. Therefore, we developed a bioinformatics method named GRACI (Gene Regulation Analysis based on Causal Inference) based on the principles of information theory, a causal inference model, and high order chromatin 3D conformation. GRACI captures the interaction and regulatory relationships between schizophrenia susceptibility genes by analyzing genotyping data. Two datasets, comprising 1459 and 2065 samples respectively, were analyzed, and the gene networks from both datasets were constructed. GRACI showcased superior accuracy when compared to widely adopted methods for detecting gene-gene interactions and intergenic regulation. This alignment was further substantiated by its correlation with chromatin high-order conformation patterns. Using GRACI, we identified three potential genes—KCNN3, KCNH1, and KCND3—that are directly associated with schizophrenia pathogenesis. Furthermore, the results of GRACI on the standalone dataset illustrated the method's applicability to other complex diseases. GRACI download: https://github.com/liuliangjie19/GRACI

Chargaff's second parity rule lies at the origin of additive genetic interactions in quantitative traits to make omnigenic selection possible.

Francis Crick's central dogma provides a residue-by-residue mechanistic explanation of the flow of genetic information in living systems. However, this principle may not be sufficient for explaining how random mutations cause continuous variation of quantitative highly polygenic complex traits. Chargaff's second parity rule (CSPR), also referred to as intrastrand DNA symmetry, defined as near-exact equalities G ≈ C and A ≈ T within a single DNA strand, is a statistical property of cellular genomes. The phenomenon of intrastrand DNA symmetry was discovered more than 50 years ago; at present, it remains unclear what its biological role is, what the mechanisms are that force cellular genomes to comply strictly with CSPR, and why genomes of certain noncellular organisms have broken intrastrand DNA symmetry. The present work is aimed at studying a possible link between intrastrand DNA symmetry and the origin of genetic interactions in quantitative traits. Computational analysis of single-nucleotide polymorphisms in human and mouse populations and of nucleotide composition biases at different codon positions in bacterial and human proteomes. The analysis of mutation spectra inferred from single-nucleotide polymorphisms observed in murine and human populations revealed near-exact equalities of numbers of reverse complementary mutations, indicating that random genetic variations obey CSPR. Furthermore, nucleotide compositions of coding sequences proved to be statistically interwoven via CSPR because pyrimidine bias at the 3rd codon position compensates purine bias at the 1st and 2nd positions. According to Fisher's infinitesimal model, we propose that accumulation of reverse complementary mutations results in a continuous phenotypic variation due to small additive effects of statistically interwoven genetic variations. Therefore, additive genetic interactions can be inferred as a statistical entanglement of nucleotide compositions of separate genetic loci. CSPR challenges the neutral theory of molecular evolution-because all random mutations participate in variation of a trait-and provides an alternative solution to Haldane's dilemma by making a gene function diffuse. We propose that CSPR is symmetry of Fisher's infinitesimal model and that genetic information can be transferred in an implicit contactless manner.

Genetic analysis of the content of palmytic acid glycerides in the carriers of maize mutation shrunken-1

Aim. The influence of corn shrunken-1 (sh1) mutation on the content of palmitate in corn oil establishing and genetic analysis of this trait. Methods. The effects of the sh1 mutation on the content of palmitate were determined by comparing the inbreds – carriers of this mutation with inbreds of the common type, as well as in the top-crosses of common type inbreds with the mutant inbreds. The genetic components of the variance in terms of the content of palmitate were analyzed in the diallel crosses of mutant inbreds according to the second Griffing method. The determination of oil fatty acid composition was carried out by the Peisker gas chromatographic method. Results. It has been established that the corn inbreds – carriers of sh1 mutation exceed the common type inbreds by an average of 29.2 % in terms of palmitate content. The level of the trait in the inbreds based on the sh1 mutation was notable as having the quantitative variability and varied within 12.2-15.6 %. The content of palmitate in the carriers of sh1 mutation was inherited as incomplete dominance with a predominant contribution of additive effects to the variance. A higher level of the trait was controlled by recessive alleles of polygenes. Conclusions. The obtained results suggests the possibility of spatial linkage of the sh1 mutant gene with palmitate-coding locus, the effect of which is modified by the polygenic complex. It has been confirmed, that the carriers of sh1 mutation expands the genetic diversity of corn in terms of palmitate content.

Gene B5 in Cotton Confers High and Broad Resistance to Bacterial Blight and Conditions High Amounts of Sesquiterpenoid Phytoalexins.

Bacterial blight resistance gene B5 has received little attention since it was first described in 1950. A near-isogenic line (NIL) of Gossypium hirsutum cotton, AcB5, was generated in an otherwise bacterial-blight-susceptible 'Acala 44' background. The introgressed locus B5 in AcB5 conferred strong and broad-spectrum resistance to bacterial blight. Segregation patterns of test crosses under Oklahoma field conditions indicated that AcB5 is likely homozygous for resistance at two loci with partial dominance gene action. In controlled-environment conditions, two of the four copies of B5 were required for effective resistance. Contrary to expectations of gene-for-gene theory, AcB5 conferred high resistance toward isogenic strains of Xanthomonas citri subsp. malvacearum carrying cloned avirulence genes avrB4, avrb7, avrBIn, avrB101, and avrB102, respectively, and weaker resistance toward the strain carrying cloned avrb6. The hypothesis that each B gene, in the absence of a polygenic complex, triggers sesquiterpenoid phytoalexin production was tested by measurement of cadalene and lacinilene phytoalexins during resistant responses in five NILs carrying different B genes, four other lines carrying multiple resistance genes, as well as susceptible Ac44E. Phytoalexin production was an obvious, but variable, response in all nine resistant lines. AcB5 accumulated an order of magnitude more of all four phytoalexins than any of the other resistant NILs. Its total levels were comparable to those detected in OK1.2, a highly resistant line that possesses several B genes in a polygenic background.

Inheritance of spike color in einkorn wheat (Triticum monococcum L.)

Aim: specify the spike color inheritance in einkorn wheat (Triticum monococcum L.) hybrids. Methods: reciprocal hybrids between the black-spikeed UA0300282 and white-spikeed UA0300311 cultivated einkorn accessions were created with the use of the “single cross” method. Four generations were analyzed using the segregation analysis method: P1, P2, F1, and F2 at autumn and spring sowing. Results: it was found that for the combination UA0300311 × UA0300282 at autumn sowing, the most suitable inheritance model is MX2-EA-AD, which implies the presence of two main genes with an equal additive effect plus polygene systems with an additive-dominant effect. In the plants of spring sowing, spike color is described by the MX2-CD-AD model, which suggests the presence of two major genes with full dominant effect plus polygenes with additive-dominant effect. In the reciprocal combination UA0300282 × UA0300311, the optimal model that describes best the spike color dispersion in plants of autumn sowing is MX2-ADI-AD, which suggests the presence of two main genes with an additive-dominant-epistatic effect plus polygenes with the additive-dominant effect. Distribution of the spring-sowing plants in terms of the spike color is well described by the MX2-ADI-ADI model – two main genes with an additive-dominant-epistatic effect plus a system of polygenes also with an additive-dominant-epistatic effect. The genes manifest themselves differently in the trait control depending on the weather conditions determined by the sowing time. In the group of direct combination plants (UA0300311 × UA0300282) of autumn sowing, heritability determined by the main gene is 97%, while that determined by polygenes is 2.7%; at spring sowing, these values are 67% and 32% respectively. In the reciprocal combination (UA0300282 × UA0300311) of autumn sowing, the main genes heritability effect is 99%, and the polygenic system accounts for 1%; in plants of spring sowing, respectively, 72%, and 28%. Conclusions: on the basis of the spike color expressiveness in the crossing combination of the einkorn kinds of wheat UA0300311 × UA0300282, the parental forms differ in two main genes and polygenes. The ratio of spike color heritability components depends on the growing conditions: at autumn sowing, 97–99 % of heritability is determined by the main genes, the polygenes account for 1–3 % of phenotypic variability; at spring sowing, the heritability component increases to 28–33 % due to the polygenic complex.

Genetic analysis of palmytic acid content in the oil of maize based on Waxy mutation

Aim. Determination of the effect of wx mutation on the palmitate content and genetic analysis of this trait in waxy maize. Methods. In two-year experiments, 10 unrelated maize inbreds of the common type and 10 inbreds – carriers of the wx mutation were analyzed. Genetic analysis of palmitate content was carried out in the diallel crosses of 6 indreds – carriers of the wx mutation by the second Griffing method. The palmitate content was determined by Peysker’s gas chromatographic method. Results. Carriers of the wx mutation of maize exceeded the maize of common type in the content of glycerides of palmitic acid in oils. The content of palmitate in unrelated inbreds – carriers of the wx mutation was subjected to quantitative variability and ranged from 13.3 % to 16.4 %. Inheritance of palmitate content in the waxy corn was carrired out by the type of incomplete dominance with a predominant contribution of additive effects to the variation. A higher level of trait was controlled by recessive alleles of polygens. Conclusions. The obtained results suggest the presence in chromosome 9 of spatial linkage of the mutant wx gene with palmitate - coding locus, the effect of which is modified by a polygenic complex.

Identification of potential blood biomarkers for early diagnosis of schizophrenia through RNA sequencing analysis

Schizophrenia (SCZ) is a highly heritable, polygenic complex mental disorder with imprecise diagnostic boundaries. Finding sensitive and specific novel biomarkers to improve the biological homogeneity of SCZ diagnosis is still one of the research hotspots. To identify the blood specific diagnostic biomarkers of SCZ, we performed RNA sequencing (RNA-seq) on 30 peripheral blood samples from 15 first-episode drug-naïve SCZ patients and 15 healthy controls (CTL). By performing multiple bioinformatics analysis algorithms based on RNA-seq data and microarray datasets, including differential expression genes (DEGs) analysis, WGCNA and CIBERSORT, we first identified 6 specific key genes (TOMM7, SNRPG, KRT1, AQP10, TMEM14B and CLEC12A) in SCZ. Moreover, we found that the proportions of lymphocyte, monocyte and neutrophils were significantly distinct in SCZ patients with CTL samples. Therefore, combining various features including age, sex and the novel blood biomarkers, we constructed the risk prediction model with three classifiers (RF: Random Forest; SVM: support vector machine; DT: decision tree) through repeated k-fold cross validation ensuring better generalizability. Finest result of Area under Receiver Operating Characteristic (AUROC) score of 0.91 was achieved by RF classifier and with a comparable good performance of AUROC 0.77 in external validation dataset. A lower AUROC of 0.63 was demonstrated when it was further applied to a Bipolar disorder (BPD) cohort. In conclusion, the study identified three peripheral core immunocytes and six key genes associated with the occurrence of SCZ, and further studies are required to test and validate these novel biomarkers for early diagnosis and treatment of SCZ.

Genome-wide association mapping in maize: status and prospects.

The online version contains supplementary material available at 10.1007/s13205-021-02799-4.

Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture.

Anterior cruciate ligament (ACL) rupture is an important condition of the human knee. Second ruptures are common and societal costs are substantial. Canine cranial cruciate ligament (CCL) rupture closely models the human disease. CCL rupture is common in the Labrador Retriever (5.79% prevalence), ~100-fold more prevalent than in humans. Labrador Retriever CCL rupture is a polygenic complex disease, based on genome-wide association study (GWAS) of single nucleotide polymorphism (SNP) markers. Dissection of genetic variation in complex traits can be enhanced by studying structural variation, including copy number variants (CNVs). Dogs are an ideal model for CNV research because of reduced genetic variability within breeds and extensive phenotypic diversity across breeds. We studied the genetic etiology of CCL rupture by association analysis of CNV regions (CNVRs) using 110 case and 164 control Labrador Retrievers. CNVs were called from SNPs using three different programs (PennCNV, CNVPartition, and QuantiSNP). After quality control, CNV calls were combined to create CNVRs using ParseCNV and an association analysis was performed. We found no strong effect CNVRs but found 46 small effect (max(T) permutation P<0.05) CCL rupture associated CNVRs in 22 autosomes; 25 were deletions and 21 were duplications. Of the 46 CCL rupture associated CNVRs, we identified 39 unique regions. Thirty four were identified by a single calling algorithm, 3 were identified by two calling algorithms, and 2 were identified by all three algorithms. For 42 of the associated CNVRs, frequency in the population was <10% while 4 occurred at a frequency in the population ranging from 10–25%. Average CNVR length was 198,872bp and CNVRs covered 0.11 to 0.15% of the genome. All CNVRs were associated with case status. CNVRs did not overlap previous canine CCL rupture risk loci identified by GWAS. Associated CNVRs contained 152 annotated genes; 12 CNVRs did not have genes mapped to CanFam3.1. Using pathway analysis, a cluster of 19 homeobox domain transcript regulator genes was associated with CCL rupture (P = 6.6E-13). This gene cluster influences cranial-caudal body pattern formation during embryonic limb development. Clustered genes were found in 3 CNVRs on chromosome 14 (HoxA), 28 (NKX6-2), and 36 (HoxD). When analysis was limited to deletion CNVRs, the association was strengthened (P = 8.7E-16). This study suggests a component of the polygenic risk of CCL rupture in Labrador Retrievers is associated with small effect CNVs and may include aspects of stifle morphology regulated by homeobox domain transcript regulator genes.

DEVELOPMENT OF INTROGRESSION LINES OF WINTER BREAD WHEAT WITH TRAITS OF RESISTANCE TO PHYTOPATHOGENS

Introduction. Wide hybridization is an important source of new genes for resistance to diseases for efficient breeding of wheat (Triticum aestivum L.) in particular due to the involvement of a wide range of an alien diversity and the ability to combine wheat and the alien resistance genes.Aim. Investigate the resistance to widespread diseases and give the breeding evaluation of the advanced introgression lines developed by repeated crosses of amphiploids, primitive lines or collection samples with modern cultivars of winter bread wheat.Methods. The field experiments were established in the crop rotation of the department of wheat breeding and seed production of PBGI–NCSCI according to the generally accepted scheme of the breeding process of self-pollinating crops. The degree of plant damage was determined on a 9-point integrated scale developed on the basis of a modified Saari and Precott scale. The protein content was determined by the Kjeldahl method, the weight of thousand kernels (WTK) by the standard method (DSTU 4138-2002).Results. A low frequency of combine of the group resistance with high yield and grain quality was registered. The genetic background of some introgression lines has been found to be favorable for realizing the positive effect of rye translocation 1BL.1RS on both economically valuable and adaptive traits in Southern Ukraine and the ability to combine with other resistance genes. A failure of a correlation of the resistance to powdery mildew, leaf and stem rusts with crop yield both in the absence and presence of a natural infectious pressure, as well as low positive connection (Rsp = 0,26 **) of the productivity with resistance to Septoria blight and yellow rust in only one variant of the experiment were established. A low significant positive correlation between the resistance and protein content and WTK, as well as between indexes of the line resistance to various diseases was observed in most cases, which is obviously a result of the artificial selection for group resistance. The breeding lines (E2792_14, AIL1161_16, E218_09, E212_09, AIL1073_16) with alien polygenic complexes for the resistance to rust diseases, high values of WTK, protein content and morphological traits; characterized by high productivity, adaptability, baking quality were isolated.Conclusions. The lines are devoid of many of the negative qualities inherent to wild species, they can be a promising source for resistance to the diseases and may be of interest for further breeding work in Southern Ukraine. Кey words: Triticum aestivum L., introgression lines, resistance, productivity.

Genetic analysis of oleic acid content in the oils of maize mutants amylose extender

Aim. Genetic analysis of oleate content in the carriers of maize mutation ae. Methods. In two-year experiments 10 unrelared on origin inbreds – carriers of ae mutation and a series of hybrids from their diallel and top-cross crossings were analysed. The analysis of the fatty acid composition of oil was carried out using a modified gas-chromatographic Peysker method. Results. It was found that the carriers of maize ae mutation are characterized by a higher oleate content compared to the maize of common type, however the oleate content in the oils of ae mutants was lower than that of the mutants su1 and su2. The different inbreds – carriers of the ae mutation differed among themselves by the the effects of the combining abilities for the oleate content in oil. The inheritance of oleate content by hybrids based on the ae mutation was similar to the type of incomplete dominance with a significant contribution of additive effects to the variance. Conclusions. In the carriers of ae maize mutation, the spatial linkage in the fifth chromosome of ae mutant gene with the oleate – encoding locus, the effect of which is modified by the polygenic complex, is likely.&#x0D; Keywords: Zea mays L., mutation ae, oleic acid, genetic analysis.

In silico analysis reveals interrelation of enriched pathways and genes in type 1 diabetes

Type 1 diabetes (T1D) is a multifactorial, polygenic complex autoimmune disease damaging pancreatic islet β cells. Numerous genes linked to T1D have been discovered through genetical studies, GWAS and polymorphisms. Most genetical studies focused on independent genes while others overemphasized on SNPs. Here, a collective analysis of documented T1D-associated genes was performed using bioinformatics tools. Enriched biological pathways, functions, enrichment clustering, networks and interactomes were analysed. Besides, meta-analyses of T1D-associated genes and T1D-related genes from SNPs were investigated to find common genes, pathways, enrichment and interrelationships. Notable enriched pathways comprised of cytokine-mediated signalling, cytokine production, interferon gamma production, myeloid leukocyte activation, activation of immune response, lymphocyte activation, adaptive immune response, Th17 cell differentiation etc. Enrichment analysis of T1D-associated genes emphasized the role of immune-linked machineries in metabolism, disease progression and aetiology of type 1 diabetes. Interactome analysis revealed overrepresentation of T1D-associated genes compared with T1D-related genes from SNPs. MCODE components highlighted the significance of pathways linked to vitamin D metabolism, signalling by interleukins, toll-like receptors, chemokines, PD-1, NOTCH, antigen processes etc. About 153 genes from MCODE complexes representing enriched pathways of T1D-associated genes and T1D-related genes from SNPs play a crucial role and may be important for further investigations. The information may be valuable for designing precision medicine-based therapeutics.

Genetic analysis of oleic acid content in the oils of maize sugary-2 mutants

Aim. Genetic analysis of oleate content in the carriers of maize mutation su2. Methods. Experiments were performed on a series of unrelated inbreeds – carriers of mutation su2 which were hybridized by the diallel and top – cross crossings. The analysis of the fatty acid composition of oil were carried out using a modified gas-chromatographic Peyskare method. Results. It was found, that su2 mutants were notable as having the increased content of oleate compared to the maize of usual type and this trait has a quantitative nature. The inbreeds – carriers of su2 mutation were significantly differed in the the effects of combining abilities for the oleate content. The inheritance of oleate was carried out by the type of incomplete dominance with the prevailing contribution of additive effects to the variance. Conclusions. In the sixth maize chromosome it is very likely that there is a spatial linkage of the su2 and oleate- encoding locus, the effect of which can be modified by the polygenic complex. Keywords: Zea mays L., mutation su2, oleic acid, genetic analysis.

Use of introgression winter bread wheat lines to increase the protein content in grain

Introduction. The problem of genetic increase in the protein content is the most important scientific and practical objective in plant breeding. Interspecies hybridization is a tools to expand the genetic diversity of wheat, in particular with respect to the protein content. Several breeding lines with alien polygenic complexes for disease resistance, high 1000-grain weight, protein content and morphological characters were obtained using crosses of original introgressive lines, collection accessions, amphiploids and elite synthetics derived from Ae. tauschii with modern wheat varieties.Aim and objectives of research. To perform comparative breeding evaluation of newly developed introgressive lines; to determine correlations between some agronomic characters and economic features; to select large-seeded, high-protein donor lines with high performance and a set of valuable characters of alien origin.Material and methods. 736 introgressive lines of bread wheat of different generations, saturation degrees and origin were studied. Generally, they were derivatives with different alien characters from distant hybridization and properties from several winter bread wheat varieties (Odesskaya 267, Albatros, Nikoniya, Selianka, Kuyalnik, Panna, Gurt), which were crossed with two original recombinant introgressive lines, one collection accession, two original amphiploids derived from Elymus sibiricus L., and six amphiploids derived from Ae. tauschii. The field experiments were laid out in compliance with the conventional design of the breeding of self-pollinating crops. The endosperm consistency and SDS30 sedimentation index were measured by the methods developed in the Department of Genetic Basics of Breeding of PBGI– NCSCI; the protein content - by the Kjeldahl digestion on a Kjeltec-Auto 1030 analyzer; 1000-grain weight – by the conventional technique; the data were statistically processed by standard methods.Results and discussion. The results of the 2015/16-2017/18 trials distinguished several lines (IL910/16, IL911/16, IL914/16, IL940/16, and IL953/16) with a high relative protein content. They are of interest for transgressive breeding for large grain and increased protein content. In addition, promising breeding lines (E196/09, E2792/14, IL299/16, IL997/16, IL1073/16, IL1100/16, IL1161/16, IL334/17, and IL480/17) combining performance equal to or higher than that of the standard, with alien complexes of disease resistance, high protein content and xeromorphic morphological characters but without negative features of wild species, were singled out.Conclusions. The studied lines may be of interest for further breeding in the South of Ukraine, provided preservation of the alien gene complexes.

Major changes of cell function and toxicant sensitivity in cultured cells undergoing mild, quasi-natural genetic drift

Genomic drift affects the functional properties of cell lines, and the reproducibility of data from in vitro studies. While chromosomal aberrations and mutations in single pivotal genes are well explored, little is known about effects of minor, possibly pleiotropic, genome changes. We addressed this question for the human dopaminergic neuronal precursor cell line LUHMES by comparing two subpopulations (SP) maintained either at the American-Type-Culture-Collection (ATCC) or by the original provider (UKN). Drastic differences in susceptibility towards the specific dopaminergic toxicant 1-methyl-4-phenylpyridinium (MPP+) were observed. Whole-genome sequencing was performed to identify underlying genetic differences. While both SP had normal chromosome structures, they displayed about 70 differences on the level of amino acid changing events. Some of these differences were confirmed biochemically, but none offered a direct explanation for the altered toxicant sensitivity pattern. As second approach, markers known to be relevant for the intended use of the cells were specifically tested. The “ATCC” cells rapidly down-regulated the dopamine-transporter and tyrosine-hydroxylase after differentiation, while “UKN” cells maintained functional levels. As the respective genes were not altered themselves, we conclude that polygenic complex upstream changes can have drastic effects on biochemical features and toxicological responses of relatively similar SP of cells.

Genetic analysis of oleic acid сontent in the oil of maize on the basis of mutation Sugary-1

Aim. Genetic analysis of oleate content in the carriers of maize mutation su1. Methods. Experiments were conducted on a series of inbreds – carriers of mutation su1, as well as hybrids derived from their diallel and top cross crossings. Results. Inbreds – carriers of mutation su1 were notable as having the increased content of oleate, which was inherited by the type of incomplete dominance with the prevailing contribution of additive effects to the variance. Conclusions. Increasing the content of the oleic acid glycerides in the carriers of mutation su1 caused by the spatial coupling of the locus su1 with the oleate – encoding locus, the effect of which can be modified by the polygenic complex.&#x0D; Keywords: Zea mays L., mutation su1, oleic acid, genetic analysis.

Dobzhansky’s concept of genetic coadaptation: Drosophila ananassae is an exception to this concept

Dobzhansky was the first to show that the inversion polymorphism in Drosophila pseudoobscura is subject to natural selection and is a device to cope with the diversity of environments. His extensive work on D. pseudoobscura has revealed interesting phenomena of population genetics. In continuation of his work on this species, he constructed a number of homozygous lines for different gene arrangements in the third chromosome, and while employing these lines in intrapopulation and interpopulation crosses, he quantified the fitness of inversion homokaryotypes and heterokaryotypes. Interestingly, his results showed that heterokaryotypes formed by chromosomes originating from the same geographic area exhibited superiority over the corresponding homokaryotypes. However, superiority of heterokaryotypes was lost in the crosses when chromosomes were derived from different localities. Based on these results, Dobzhansky suggested the concept of genetic coadaptation. According to this concept, 'in each locality, the chromosomes with different gene arrangements aremutually adjusted or coadapted to yield highly fit inversion heterozygotes through long continued natural selection. However, this adaptive superiority of inversion heterozygotes breaks down in interracial hybridization experiments when two gene arrangements are derived from different localities'. This concept has received experimental evidence in its favour on the basis of work done in other species of Drosophila, such as D. willistoni, D. paulistorum, D. pavani and D. bipectinata. In all these species, interracial hybridization led to the loss of superiority of inversion heterozygotes. Further, it has been suggested that coadapted polygenic complexes contained in the chromosomes are disrupted as a result of recombination in interstrain crosses. This concept was also tested in D. ananassae, a cosmopolitan and domestic species commonly found in India, while employing three cosmopolitan inversions exhibiting heterotic buffering. In interstrain crosses involving monomorphic and polymorphic strains due to three cosmopolitan inversions, the persistence of heterosis was observed, which does not support the above-mentioned hypothesis of Dobzhansky. Thus, evidence for coadaptation is lacking in natural populations of D. ananassae, which is considered as an exception to the Dobzhansky's concept of genetic coadaptation. Thus, heterotic buffering associated with the three cosmopolitan inversions in D. ananassae is not populational heterosis; rather, it appears to be simple luxuriance.

Established Type 2 Diabetes–Susceptibility Genetic Variants in Saudi ethnicity: A Mini-Systematic Review

Type 2 Diabetes (T2D) is a polygenic and multi-factorial complex disease. The significant challenge of finding genetic markers that could be used to predict T2D risk remains unresolved. Saudi Arabia is one of several ethnicities with a high prevalence rate of T2D. A large number of studies have been performed that explored genetic factors associated with T2D risk. In this work, we conducted a systematic review of published studies on T2D genetic markers in the Saudi population. Multiple databases were employed in the literature review, which focused on studies that either reported the association or non-association of a genetic marker with T2D risk. Using appropriate search terms, we collected, analyzed, and selected 428 articles published between the years of 2000-2018, Of these, 18 articles reported a total of 67 polymorphisms in 46 genes that are strongly linked to T2D in the Saudi population. Most of the relevant studies used genotyping as the primary methodology to identify genetic markers of T2D. Most of these studies were published between the years of 2012-2017. A total of 23 polymorphisms in 17 genes were found to be associated with T2D risk in the Saudi population: KCNJ11, PPARG2, IRS1, VDE, WFS1, JAZF1, CDKN2A/B, TCF7L2, KCNQ1, HNF4A, DUSP9, APOE, HNF1A, SLC30A8, APOC3, SNAP25, and ACE.

Genome-wide compound heterozygote analysis highlights alleles associated with adult height in Europeans

Adult height is the most widely genetically studied common trait in humans; however, the trait variance explainable by currently known height-associated single nucleotide polymorphisms (SNPs) identified from the previous genome-wide association studies (GWAS) is yet far from complete given the high heritability of this complex trait. To exam if compound heterozygotes (CH) may explain extra height variance, we conducted a genome-wide analysis to screen for CH in association with adult height in 10,631 Dutch Europeans enriched with extremely tall people, using our recently developed method implemented in the software package CollapsABEL. The analysis identified six regions (3q23, 5q35.1, 6p21.31, 6p21.33, 7q21.2, and 9p24.3), where multiple pairs of SNPs as CH showed genome-wide significant association with height (P < 1.67 × 10−10). Of those, 9p24.3 represents a novel region influencing adult height, whereas the others have been highlighted in the previous GWAS on height based on analysis of individual SNPs. A replication analysis in 4080 Australians of European ancestry confirmed the significant CH-like association at 9p24.3 (P < 0.05). Together, the collapsed genotypes at these six loci explained 2.51% of the height variance (after adjusting for sex and age), compared with 3.23% explained by the 14 top-associated SNPs at 14 loci identified by traditional GWAS in the same data set (P < 5 × 10−8). Overall, our study empirically demonstrates that CH plays an important role in adult height and may explain a proportion of its “missing heritability”. Moreover, our findings raise promising expectations for other highly polygenic complex traits to explain missing heritability identifiable through CH-like associations.

The first U–Pb isotope age data of island arc and continental–margin magmatism in the central part of the Koryak Highlands and U–Pb age of ore-controlling granitoids of the talyayigin ore field

Precision U–Pb (SHRIMP-II) isotope geochronological data, obtained for the first time, make it possible to suggest that sediments of the Neocomian primitive island arc sequence are missed or poorly developed in the South-Western part of the Mainitskii terrane of the Koryak Highlands. However, Late Albian mature island arc tuff and tuffaceous–turbidite formations are common. This enables us to extend the age range of the Mainitskii island arc from the Early Neocomian to the Late Albian and to suggest a two-stage pattern of its development. The isotope-geochronological data obtained for plagiogranite and moderately acid subvolcanics, previously attributed to the Koryak–Western Kamchatka volcanoplutonic belt, indicate that it is possible to combine them into the Middle Miocene postsubduction? polygenic complex. In addition, owing to modern high-precision isotope–geochronological methods, it has become possible to determine the age of gold–sulfide mineralization of the Talyaigin ore field, paragenetically related to the manifestations of the Middle Miocene Vilyuneiveem complex.