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"Black Copper Walking on Silver ", the unique copper production process in Yunnan, as an important part of the excellent traditional Chinese culture, its inheritance has far-reaching significance for us to establish cultural confidence and rebuild cultural identity. However, the current development of black copper and silver walking technology is difficult, and the traditional sense of protection has been unable to solve the root problem. Nowadays, the protection of black copper and silver walking skills should break the traditional static single protection mode, combine the traditional inheritance with modern protection, and grasp the intangible cultural heritage elements from the perspective of productive protection. On the basis of objectively analyzing the characteristics and development status, the article effectively connects the living inheritance with industrialization, and explores the new development mode of folk custom industrialization under the live inheritance mode, so as to promote the live inheritance of black copper walking on silver and the common development of folk economy industry.

Forkhead box (FOX) proteins are members of a conserved family of transcription factors. Pathogenic variants in FOX genes have been shown to be responsible for several human genetic diseases. Here, we have studied the molecular and structural features of germline pathogenic variants in seven FOX proteins involved in Mendelian disorders and compared them with those of variants present in the general population (gnomAD). Our study shows that the DNA-binding domain of FOX proteins is particularly sensitive to damaging variation, although some family members show greater mutational tolerance than others. Next, we set to demonstrate that this tolerance depends on the inheritance mode of FOX-linked disorders. Accordingly, genes whose variants underlie recessive conditions are supposed to have a greater tolerance to variation. This is what we found. As expected, variants responsible for disorders with a dominant inheritance pattern show a higher degree of pathogenicity compared to those segregating in the general population. Moreover, we show that pathogenic and likely pathogenic variants tend to affect mutually exclusive sites with respect to those reported in gnomAD. The former also tend to affect sites with lower solvent exposure and a higher degree of conservation. Our results show the value of using publicly available databases and bioinformatics to gain insights into the molecular and structural bases of disease-causing genetic variation.

Background Dusky cotton bug (DCB), Oxycarenus hyalinipennis (Costa) (Hemiptera: Lygaeidae), is a key insect pest of cotton. It causes huge losses to cotton and many other economically important crops. Sulfoxaflor is a newly introduced systemic insecticide that is effective against many sap-feeding insect pests such as aphids, whiteflies and true bugs. The present study was designed to characterize the inheritance of sulfoxaflor resistance in DCB. Moreover, the role of synergists in reducing sulfoxaflor resistance in DCB was also assessed. Results A field population of DCB has developed 1132.0-fold resistance to sulfoxaflor after 11 selected generations in the laboratory. Nonsignificant difference of reciprocal crosses was observed depending on the LC50 (median lethal concentration) values (95% confidence intervals overlapped), suggesting an autosomal mode of sulfoxaflor resistance inheritance. The degree of dominance of 0.7 for F1 (Sulfo-Sel Pop ♀ × Lab-Pop♂) and 0.6 for F1 '(Sulfo-Sel Pop ♂ × Lab-Pop♀), respectively, suggested that sulfoxaflor resistance was incompletely dominant. According to the monogenic model, the number of genes involved to induce sulfoxaflor resistance revealed that sulfoxaflor resistance was polygenic in nature. The realized heritability (h2 ) value for sulfoxaflor resistance was 0.2. The synergists experiment indicated that esterases were involved in the sulfoxaflor resistance mechanism in DCB. Conclusions The current results indicate that there is autosomal, incompletely dominant and polygenic inheritance of sulfoxaflor resistance in DCB. Our results would be helpful in delaying sulfoxaflor resistance against DCB in the field. © 2021 Society of Chemical Industry.

Previous studies using additive genetic models failed to identify robust evidence of associations between colorectal cancer (CRC) risk variants and survival outcomes. However, additive models can be prone to false negative detection if the underlying inheritance mode is recessive. Here, we tested all currently known CRC-risk variants (n = 129) in a discovery analysis of 5675 patients from a Scottish cohort. Significant associations were then validated in 2474 CRC cases from UK Biobank. We found that the TT genotype of the intron variant rs7495132 in the CRTC3 gene was associated with clinically relevant poorer CRC-specific survival in both the discovery (HR = 1.97, 95% CI = 1.41-2.74, P = 6.1x10-5 ) and validation analysis (HR = 1.69, 95% CI = 1.03-2.79, P = 0.038). In addition, the GG genotype of rs10161980 (intronic variant of AL139383.1 lncRNA) was associated with worse overall survival in the discovery cohort (HR = 1.24, 95% CI = 1.10-1.39, P = 3.4x10-4 ) and CRC-specific survival in the validation cohort (HR = 1.26, 95% CI = 1.01-1.56, P = 0.040). Our findings show that common genetic risk factors can also influence CRC survival outcome. This article is protected by copyright. All rights reserved.

Social transformation and inheritance of national traditional sports culture are the inevitable trends of modernization development. Social transformation has led to great changes in social environment, economic structure, culture and values. This change has affected the development space, development path and inheritance mode of national traditional sports culture to a certain extent. In order to better inherit China’s national sports culture under social transformation and promote the innovative development of China’s traditional culture, it is necessary to effectively explore the relationship between social transformation and cultural inheritance, so as to make social progress, establish local, value coexistence, integration and innovation, and make culture better serve the society.

The development and inheritance of jade carving skills are the foundation of jade culture rooted in China. At present, the jade carving industry has entered a brand new period. With the rise and development of jade carving design in higher-level education, the traditional model of mentoring inheritance is obviously not applicable to the modern higher education system. Through the combing of the jade carving inheritance method, the advantages and disadvantages of each inheritance method can be effectively summarized. We should draw lessons from the advantages of the traditional inheritance mode, combined with the current higher education mode and resources. On the basis of the existing teaching mode, jade carving teaching methods more suitable for the modern higher education system are explored. It is helpful to cultivate high-quality jade carving talents with high design level and practical technical level. The inheritance mode of higher education and the accumulation of talent training will become an important carrier and channel for jade carving art inheritance in the future.

The influencing factors of kite culture inheritance form a complex system that is influenced by many factors, such as the inheritance mode, audience preferences, communication mode and social environment, and the influencing factors are plentiful and nonlinear. In this paper, we use the literature search method and Delphi method to determine the set of influencing factors and clarify the direct binary relationships between each of them. Based on the results of these methods, the Adversarial Interpretive Structure Model (AISM) is modeled and used, and the AISM model with a cause-effect reachable hierarchy is obtained by comparing the directed topological diagram of a pair of up and down diagrams and conducting a comprehensive analysis of the influencing factors of kite culture inheritance. Finally, the validity of the model is proved through the project practice of talent training in the National Art Foundation of China. The results of this study show the following: policies and regulations and product characteristics are the root cause elements affecting the inheritance of intangible cultural heritage.

The dusky cotton bug (DCB), Oxycarenus hyalinipennis Costa (Hemiptera: Lygaeidae) is one of the most important pests of cotton. Fipronil belongs to phenylpyrazole and is being used against various insect pests. To reduce the resistance to this insecticide, the present study was planned to examine the inheritance mode and preliminary mechanism of resistance to fipronil in DCB. A fipronil selected strain had a 9855-fold level of resistance after 11 generations of selection with fipronil. The median lethal concentration of reciprocal crosses F1 (Fipro-Sel.♂×Lab-Pop♀) and F1-(Fipro-Sel.♀× Lab-Pop♂) showed no significant difference and degree of dominance values were 0.60 and 0.58 for F1 and F1-), respectively, suggesting autosomal and incompletely dominance of resistance to fipronil in fipronil selected strain of DCB. Monogenic model of inheritance revealed polygenic resistance to fipronil. Realized heritability (h2) value was 0.24 for fipronil resistance. The study of synergism indicated that PBO (Piperonyl butoxide) and DEF (S, S-butyl phosphorotrithioateases) did not enhance the toxicity of fipronil on both populations. The study on inheritance mode of fipronil resistance in DCB may help delay the resistance with insecticides.

Alport syndrome (AS) is a progressive inherited kidney disease characterized by hearing loss and ocular abnormalities. There are three forms of AS depending on inheritance mode: X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, which encodes type IV collagen α5 chain, while ADAS and ARAS are caused by variants in COL4A3 or COL4A4, which encode type IV collagen α3 or α4 chain, respectively. In male XLAS or ARAS cases, end-stage kidney disease (ESKD) develops around a median age of 20 to 30 years old, while female XLAS or ADAS cases develop ESKD around a median age of 60 to 70 years old. The diagnosis of AS is dependent on either genetic or pathological findings. However, determining the pathogenicity of the variants detected by gene tests can be difficult. Recently, we applied the following molecular investigation tools to determine pathogenicity: 1) in silico and in vitro trimer formation assay of α345 chains to assess triple helix formation ability, 2) kidney organoids constructed from patients' induced pluripotent stem cells to identify α5 chain expression on the glomerular basement membrane, and 3) in vitro splicing assay to detect aberrant splicing to determine the pathogenicity of variants. In this review article, we discuss the genetic background and novel assays for determining the pathogenicity of variants. We also discuss the current treatment approaches and introduce exon skipping therapy as one potential treatment option.

Backgrounds MUTYH‐associated polyposis (MAP) is an autosomal recessive disease caused by biallelic pathogenic variants (PV) of the MUTYH gene. The aim of this study was to investigate the genetic causes of unexplained polyposis patients with monoallelic MUTYH PV. The analysis focused on 26 patients with suspected MAP, belonging to 23 families. Ten probands carried also one or more additional MUTYH variants of unknown significance. Methods Based on variant type and on the collected clinical and molecular data, these variants were reinterpreted by applying the ACMG/AMP rules. Moreover, supplementary analyses were carried out to investigate the presence of other variants and copy number variations in the coding and promoter regions of MUTYH, as well as other polyposis genes (APC, NTHL1, POLE, POLD1, MSH3, RNF43, and MCM9). Results We reclassified 4 out of 10 MUTYH variants as pathogenic or likely pathogenic, thus supporting the diagnosis of MAP in only four cases. Two other patients belonging to the same family showed a previously undetected deletion of the APC gene promoter. No PVs were found in the other investigated genes. However, 6 out of the 18 remaining families are still interesting MAP candidates, due to the co‐presence of a class 3 MUTYH variant that could be reinterpreted in the next future. Conclusion Several efforts are necessary to fully elucidate the genetic etiology of suspected MAP patients, especially those with the most severe polyposis/tumor phenotype. Clinical data, tumor molecular profile, family history, and polyposis inheritance mode may guide variant interpretation and address supplementary studies., The aim of this study was to investigate the genetic causes of unexplained polyposis patients with monoallelic MUTYH pathogenic variants. Clinical data, tumor molecular profile, family history, and polyposis inheritance mode may guide MUTYH variant interpretation and address supplementary studies of additional polyposis risk genes.

Dupuytren contracture (DC) is predominantly an autosomal dominant disorder characterized by hypertrophy and contraction of the palmar fascia that results in tethered flexion of the affected digits. It has its highest prevalence in the North European population or in people of Viking descent, and its incidence is growing with age. DC shares a common inheritance mode, predisposing factors, comorbidities, pathophysiology, and evolution with Ledderhose disease, Garrod knuckle pads, and Peyronie disease. Nonmelanoma skin cancer also has a higher incidence in the population of North European phenotype and apparently a common genetic polymorphism. Psoriasis shares many risk factors and comorbidities with DC and has a higher prevalence in patients with DC. We suggest a close relationship among DC, some skin malignancies, and psoriasis. Regular monitoring for those skin diseases in all patients with DC is highly recommended.

Background Pathogenic variants in human phospholamban coding gene (PLN) are known to cause hereditary dilated cardiomyopathy with heart failure in an autosomal dominant mode. Methods We performed high-depth targeted next-generation sequencing using a cardiomyopathy-panel containing 80 disease-related genes in 650 unrelated patients with non-ischemic cardiomyopathy to identify potential pathogenic PLN variants. To comprehensively evaluate the genetic cause of the proband and his pedigree, whole-exome sequencing and Sanger sequencing were performed. Results A novel homozygous nonsense variant (p.Glu2Ter, c.4G>T) in PLN was identified in a 36-year-old male suffering from dilated cardiomyopathy with severe heart failure. No more cardiomyopathy-causing variant or likely pathogenic copy number variation was identified. This variant was not detected in 800 unrelated healthy controls. Furthermore, the variant is not in the Exome Aggregation Consortium or the Genome Aggregation databases. Western blots showed that this variant significantly reduced the expression of phospholamban. Furthermore, in pedigree analysis, we found that all five heterozygous PLN-p.Glu2Ter carriers (including four elder relatives) had normal heart size and cardiac function, which revealed a novel autosomal recessive inheritance mode. Conclusions Our study identified a novel pathogenic variant of PLN, and revealed a novel pathogenic inheritance mode of PLN causing dilated cardiomyopathy with heart failure.

Summary/AbstractWhole-genome duplications yield varied chromosomal pairing patterns, ranging from strictly bivalent to multivalent, resulting in disomic and polysomic inheritance modes. In the bivalent case, homeologous chromosomes form pairs, where in a multivalent pattern all copies are homologous and are therefore free to pair and recombine. As sufficient sequencing data is more readily available than high-quality cytological assessments of meiotic behavior or population genetic assessment of allelic segregation, especially for non-model organisms, here we describe two bioinformatics approaches to infer origins and inheritance modes of polyploids using short-read sequencing data. The first approach is based on distributions of allelic read depth at the heterozygous sites within an individual, as the expectations of such distributions are different for disomic and polysomic inheritance modes. The second approach is more laborious and based on a phylogenetic assessment of partially phased haplotypes of a polyploid in comparison to the closest diploid relatives. We discuss the sources of deviations from expected inheritance patterns, advantages and pitfalls of both methods, effects of mating types on the performance of the methods, and possible future developments.

Mutation rate plays an important role in adaptive evolution due to its effect on the rate of appearance of both beneficial and deleterious mutations and is therefore subject to second-order selection. The mutation rate varies between and within species and populations, increases under some stresses, and can be modified by mutator and anti-mutator alleles. It may also vary among genetically identical individuals: empirical evidence from bacteria suggests that the mutation rate can be affected by translation errors and expression noise in various proteins. Importantly, this non-genetic variation may be heritable via a transgenerational epigenetic mode of inheritance, giving rise to mutator phenotype switching that is independent from mutator alleles. Here we investigate mathematically how the rate of adaptive evolution on rugged, complex fitness landscapes is affected by the rate of mutation rate phenotype switching. Motivated by recent experimental results of mutation rate variation, we model an asexual population with two mutation rate phenotypes, non-mutator and mutator. An offspring may switch from its parental phenotype to the other phenotype. Thus, the mutation rate can be interpreted as a genetically inherited trait when the switching rate is low, as an epigenetically inherited trait when the switching rate is intermediate, or as a randomly determined trait when the switching rate is high. We find that intermediate switching rates maximize the rate of adaptation on rugged fitness landscapes. This is because an intermediate switching rate can maintain within the same individuals both a mutator phenotype and pre-existing mutations, a combination that facilitates the crossing of fitness valleys. Further, intermediate switching rates allow the population to quickly revert to a low mutation rate after adaptation is achieved, avoiding the accumulation of deleterious mutations linked to mutator alleles. Our results rationalize recently observed noise in the expression of proteins that affect the mutation rate and suggest that non-genetic inheritance of this phenotype may facilitate evolutionary adaptive processes.

Background Triflumezopyrim, a novel commercialized mesoionic chemical insecticide, has been confirmed as a promising insecticide for efficiently controlling the brown planthopper, Nilaparvata lugens (Stal). Here, a laboratory triflumezopyrim-resistant (TR) strain and an isogenic susceptible (TS) strain were established to characterize the inheritance and fitness costs of triflumezopyrim resistance in N. lugens. Results After 29 generations of successive selection with triflumezopyrim, the TR strain developed a 155.23-fold higher resistance level than the TS strain. The median lethal concentration (LC50 ) values from progenies (F1 RS and F1 SR) of reciprocal crosses between TR and TS strains suggested that triflumezopyrim resistance in N. lugens was autosomal and codominant. Chi-square analyses of self-bred and backcrossed progenies suggested that the resistance results from a polygenic effect. Compared to the TS strain, the TR strain showed a lower relative fitness (0.62) with a significantly decreased female adult period, longevity, total fecundity, egg hatchability, intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0 ), and prolonged pre-adult period and total preoviposition period (TPOP). Conclusion The inheritance mode of triflumezopyrim resistance in N. lugens was characterized as autosomal, codominant and polygenic. The resistance had a fitness cost, which may be an important factor limiting the evolution of resistance. These findings provide valuable information for optimizing resistance management strategies to delay triflumezopyrim resistance development and maintain sustainable control of N. lugens. © 2021 Society of Chemical Industry.

Metazoans usually reproduce sexually, blending the unique identity of parental genomes for the next generation through functional crossing-over and recombination in meiosis. However, some metazoan lineages have evolved reproductive systems where offspring are either full (clonal) or partial (hemiclonal) genetic replicas. In the latter group, the process of uniparental genome elimination selectively eliminates either the maternal or paternal genome from germ cells, and only one parental genome is selected for transmission. Although fairly common in plants, hybridogenesis (i.e., clonal haploidization via chromosome elimination) remains a poorly understood process in animals. Here, we explore the proximal cytogenomic mechanisms of somatic and germ cell chromosomes in sexual and hybrid genotypes of Australian carp gudgeons (Hypseleotris) by tracing the fate of each set during mitosis (in somatic tissues) and meiosis (in gonads). Our comparative study of diploid hybrid and sexual individuals revealed visually functional gonads in male and female hybrid genotypes and generally high karyotype variability, although the number of chromosome arms remains constant. Our results delivered direct evidence for classic hybridogenesis as a reproductive mode in carp gudgeons. Two parental sets with integral structure in the hybrid soma (the F1 constitution) contrasted with uniparental chromosomal inheritance detected in gonads. The inheritance mode happens through premeiotic genome duplication of the parental genome to be transmitted, whereas the second parental genome is likely gradually eliminated already in juvenile individuals. The role of metacentric chromosomes in hybrid evolution is also discussed.

This study is the first to evaluate familial aggregation, heritability and inheritance mode of type 2 diabetes (T2D) in Tehran Lipid Glucose Study (TLGS) participants as a representative sample of the Iranian population.From the ongoing family-based TLGS cohort, 13,741 individuals at least 20 years of age (mean ± standard deviation, 39.71±16.56) were assessed. After correcting family structures using genomic information from the Tehran Cardiometabolic Genetic Study, 2,594 constituent pedigrees were constructed. Familial aggregation was assessed based on genealogic index testing, familial intraclass correlation and positive family history. Family-based heritability was checked with 2 linear mixed models, including 2 different random components: the kinship matrix and the genomic relationship matrix. The mode of inheritance of T2D was investigated by complex segregation analysis (CSA).Familial aggregation of T2D was significant (p0.05), and family-based heritability showed a high degree of genetic variation in T2D between individuals at 65% (standard error, 0.034). Within first-degree relatives (parent/offspring and siblings), the likelihood of a parental affect was higher than in siblings (odds ratio, 4.11 vs 1.65). Family history of T2D among first-degree relatives was more noteworthy than for second-degree relatives (odds ratio, 3.84 vs 0.59). CSA revealed that the polygenic model is best to illustrate the mode of inheritance of T2D for TLGS participants.Our findings demonstrate that the heritability of T2D with polygenic mode in the Iranian population is higher than the global average. We also found that T2D is transmitted equally into siblings, with parental affect the leading risk factor. These data suggest that policymakers should change individual-level to family-level prevention.

Infantile epileptic encephalopathy-9 (EIEE9) is a developmental and epileptic encephalopathy (DEE) with infantile onset of clusters of focal seizures triggered by febrile illness and subsequent intellectual disability, autism spectrum disorder, and psychiatric comorbidity in most patients. This pathology is due to de novo or inherited mutations in the X-chromosome gene PCDH19 (Xq22.1), and its inheritance mode is peculiar since healthy carrier fathers transmit the mutations to their affected daughters. Therefore a “cell-interference model” has been hypothesized, according to which PCDH19-related DDE (PCDH19-DDE) symptoms would arise from the coexistence of PCDH19-positive and PCDH19-negative cells, as a consequence of the random X-chromosome inactivation in females. PCDH19 is emerging as a cell-adhesion molecule broadly involved in several core stages of neurodevelopment, from neurulation to neuronal network wiring passing through cell migration and proliferation. Despite PCDH19-DDE treatments still representing an open battle, the ongoing research on PCDH19 biological function is expected to provide important therapeutic hints.

In China, there is a crisis of rural cultural heritage inheritance due to urbanization. The traditional cultural inheritance modes such as building museums may not satisfy the needs of wide and fast culture transmission, communication, and inheritance. However, the virtual museum may provide new solutions. Nowadays, China has essential social-economic conditions for virtual museum construction but lacks sustainable modes for virtual museums supporting rural cultural heritage inheritance. In this study, we adopted the theoretical analysis method, expert argumentative method, and combined with virtual museum technology analysis to design an appropriate mode for the cultural heritage’s inheritance in rural areas. We built a demonstrational virtual museum for the Mt. Mogan government according to this mode, adopted a comparative analysis and questionnaire survey to verify, and assess the application effects of the mode. Results show that the inheritance mode of rural cultural heritage based on the virtual museum has advantages of larger exhibition scale and wider scope of cultural transmission and communication with less input, and this mode’s operation is steady and sustainable. The inheritance crisis of rural cultural heritage needs reasonable solutions, and our results can be a guideline for building virtual museums in rural areas to promote wide, fast, and sustainable cultural inheritance.

Forensic genetic laboratories perform a large amount of STR analyses of the Y chromosome, in particular to analyze the male part of complex DNA mixtures. However, the statistical interpretation of evidence retrieved from Y-STR haplotypes is challenging. Due to the uni-parental inheritance mode, Y-STR loci are connected to each other and thus haplotypes show patterns of relationship on the familial and population level. This precludes the treatment of Y-STR loci as independently inherited variables and the application of the product rule. Instead, the dependency structure of Y-STRs needs to be included in the haplotype frequency estimation process affecting also the current paradigm of a random match probability that is in the autosomal case approximated by the population frequency assuming unrelatedness of sampled individuals. Information on the degree of paternal relatedness in the suspect population as well as on the familial network is however needed to interpret Y-chromosomal results in the best possible way. The previous recommendations of the DNA commission of the ISFG on the use of Y-STRs in forensic analysis published more than a decade ago [1] cover the interpretation issue only marginally. The current recommendations address a number of topics (frequency estimators, databases, metapopulations, LR formulation, triage, rapidly mutating Y-STRs) with relevance for the Y-STR statistics and recommend a decision-based procedure, which takes into account legal requirements as well as availability of population data and statistical methods.

Along with traditional effects of aging and carcinogen exposure—inherited DNA variation has substantial contribution to cancer risk. Extraordinary progress made in analysis of common variation with GWAS methodology does not provide sufficient resolution to understand rare variation. To fulfill missing classification for rare germline variation we assembled dataset of whole exome sequences from>2000 patients (selected cases tested negative for candidate genes and unselected cases) with different types of cancers (breast cancer, colon cancer, and cutaneous and ocular melanomas) matched to more than 7000 non-cancer controls and analyzed germline variation in known cancer predisposing genes to identify common properties of disease-associated DNA variation and aid the future searches for new cancer susceptibility genes. Cancer predisposing genes were divided into non-overlapping classes according to the mode of inheritance of the related cancer syndrome or known tumor suppressor activity. Out of all classes only genes linked to dominant syndromes presented significant rare germline variants enrichment in cases. Separate analysis of protein-truncating and missense variation in this list of genes confirmed significant prevalence of protein-truncating variants in cases only in loss-of-function tolerant genes (pLI 0.9). In addition to findings in genetically enriched cases, we observed significant burden of rare variation in unselected cases, suggesting substantial role of inherited variation even in relatively late cancer manifestation. Taken together, our findings provide reference for distribution and types of DNA variation underlying inherited predisposition to some common cancer types.

Background Germ lines are the cell lineages that give rise to the sperm and eggs in animals. The germ lines first arise from primordial germ cells (PGCs) during embryogenesis: these form from either a presumed derived mode of preformed germ plasm (inheritance) or from an ancestral mechanism of inductive cell-cell signalling (induction). Numerous genes involved in germ line specification and development have been identified and functionally studied. However, little is known about the molecular evolutionary dynamics of germ line genes in metazoan model systems. Results Here, we studied the molecular evolution of germ line genes within three metazoan model systems. These include the genus Drosophila (N=34 genes, inheritance), the fellow insect Apis (N=30, induction), and their more distant relative Caenorhabditis (N=23, inheritance). Using multiple species and established phylogenies in each genus, we report that germ line genes exhibited marked variation in the constraint on protein sequence divergence (dN/dS) and codon usage bias (CUB) within each genus. Importantly, we found that de novo lineage-specific inheritance (LSI) genes in Drosophila (osk, pgc) and in Caenorhabditis (pie-1, pgl-1), which are essential to germ plasm functions under the derived inheritance mode, displayed rapid protein sequence divergence relative to the other germ line genes within each respective genus. We show this may reflect the evolution of specialized germ plasm functions and/or low pleiotropy of LSI genes, features not shared with other germ line genes. In addition, we observed that the relative ranking of dN/dS and of CUB between genera were each more strongly correlated between Drosophila and Caenorhabditis, from different phyla, than between Drosophila and its insect relative Apis, suggesting taxonomic differences in how germ line genes have evolved. Conclusions Taken together, the present results advance our understanding of the evolution of animal germ line genes within three well-known metazoan models. Further, the findings provide insights to the molecular evolution of germ line genes with respect to LSI status, pleiotropy, adaptive evolution as well as PGC-specification mode. Electronic supplementary material The online version of this article (10.1186/s12862-019-1363-x) contains supplementary material, which is available to authorized users.

Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring. Elucidating the molecular mechanism for this unusual mode of inheritance will provide new insights into how mtDNA is passed on from parent to offspring and may even lead to the development of new avenues for the therapeutic treatment for pathogenic mtDNA transmission.

Dusky cotton bug, Oxycarenus hyalinipennis (Hemiptera: Lygaeidae) has become a notorious pest of cotton due to widespread use of Bt cotton. Imidacloprid is a broad spectrum neonicotinoid that has been used for the control of various insect pests worldwide. This study was conducted to explore the genetic mode of imidacloprid resistance in O. hyalinipennis. Continuous selection with imidacloprid for nine generations produced a high level of resistance (104-fold). The CI intervals of LC50 values of both reciprocal crosses (F1 and F1′) were overlapping, exhibiting an autosomal mode of inheritance. The heritability value was 0.33 for imidacloprid resistance. A monogenic model of inheritance revealed that more than one factor is involved in imidacloprid resistance. Imidacloprid resistance in O. hyalinipennis was autosomal, incompletely dominant and polygenic. The present study suggested that such high level of resistance can be controlled by alternating use of insecticides with different modes of action along with timely and accurate application of imidaclopid.

FBLN5-related cutis laxa (CL) is a rare syndrome that can be inherited in an autosomal dominant or recessive manner. Autosomal recessive cutis laxa (ARCL), type IA, has been reported to be more severe. The disease is characterized by microcephaly, sagging cheeks, loose, wrinkled and redundant skin, emphysema, aorta or pulmonary artery abnormalities, inguinal hernia, and anomalies of internal organs. Homozygous mutations in the FBLN5 gene are responsible for the clinical manifestations. We report a family study of a child with ARCL. FBLN5 genes of the patient and parents were sequenced using next-generation sequencing technologies. Analyses showed that the patient was homozygous for the novel c.518A>G, p.R173H mutation in exon 6 of the FBLN5 gene, whereas the parents were heterozygous. The mutation was found to be 'possibly pathogenic' in bioinformatic analysis. We identified a novel FBLN5 mutation in a CL patient; pedigree and parental genetic analyses suggested ARCL. Our results also suggest that the mutation analysis provides useful evidence to support the clinical diagnosis and define the inheritance mode of CL in an apparently sporadic case.

Motivation The use of single nucleotide polymorphism (SNP) interactions to predict complex diseases is getting more attention during the past decade, but related statistical methods are still immature. We previously proposed the SNP Interaction Pattern Identifier (SIPI) approach to evaluate 45 SNP interaction patterns/patterns. SIPI is statistically powerful but suffers from a large computation burden. For large-scale studies, it is necessary to use a powerful and computation-efficient method. The objective of this study is to develop an evidence-based mini-version of SIPI as the screening tool or solitary use and to evaluate the impact of inheritance mode and model structure on detecting SNP–SNP interactions. Results We tested two candidate approaches: the ‘Five-Full’ and ‘AA9int’ method. The Five-Full approach is composed of the five full interaction models considering three inheritance modes (additive, dominant and recessive). The AA9int approach is composed of nine interaction models by considering non-hierarchical model structure and the additive mode. Our simulation results show that AA9int has similar statistical power compared to SIPI and is superior to the Five-Full approach, and the impact of the non-hierarchical model structure is greater than that of the inheritance mode in detecting SNP–SNP interactions. In summary, it is recommended that AA9int is a powerful tool to be used either alone or as the screening stage of a two-stage approach (AA9int+SIPI) for detecting SNP–SNP interactions in large-scale studies. Availability and implementation The ‘AA9int’ and ‘parAA9int’ functions (standard and parallel computing version) are added in the SIPI R package, which is freely available at https://linhuiyi.github.io/LinHY_Software/. Supplementary information Supplementary data are available at Bioinformatics online.

International audience; Hereditary spastic paraplegias (HSP) are neurodegenerative disorders characterized by lower limb spasticity and weakness that can be complicated by other neurological or non-neurological signs. Despite a high genetic heterogeneity (460 causative genes), 40–70% of the families remain without a molecular diagnosis. Analysis of one of the pioneer cohorts of 193 HSP families generated in the early 1990s in Portugal highlighted that SPAST and SPG11 are the most frequent diagnoses. We have now explored 98 unsolved families from this series using custom next generation sequencing panels analyzing up to 70 candidate HSP genes. We identified the likely disease-causing variant in 20 of the 98 families with KIF5A being the most frequently mutated gene. We also found 52 variants of unknown significance (VUS) in 38% of the cases. These new diagnoses resulted in 42% of solved cases in the full Portuguese cohort (81/193). Segregation of the variants was not always compatible with the presumed inheritance, indicating that the analysis of all HSP genes regardless of the inheritance mode can help to explain some cases. Our results show that there is still a large set of unknown genes responsible for HSP and most likely novel mechanisms or inheritance modes leading to the disease to be uncovered, but this will require international collaborative efforts, particularly for the analysis of VUS.

Hereditary spastic paraplegia (HSP) includes a group of clinically and genetically heterogeneous disorders with multiple genetic loci participating in its pathogenesis. Here we report three Iranian patients with HSP. Molecular analyses revealed that they have mutations in AP4M1 gene (NM_004722:c.802C>T, p.R268X and c.1225T>C, p.F409L) and AP4E1 gene (NM_007347: c.3212_3213delCT, p.L1072Afs*10). All of them were born to consanguineous parents. Genetic diagnosis was performed using whole exome sequencing (WES), Sanger sequencing and segregation analysis. Due to heterogeneity in clinical manifestations and inheritance mode as well as the presence of different causative genes in HSP, WES facilitates the diagnosis and provides opportunity for prenatal diagnosis in families with affected members.

Tooth impaction is a pathological condition where a tooth fails to attain its normal functional position. The present study aims to highlight the phenotypic heterogeneity of impacted third molars in a Caucasian family, to investigate the characteristics of the dental phenotype, to evidence the diversity of dental phenotype, and to identify the inheritance mode of the condition. Detailed anamnesis, clinical examination, complementary tests (panoramic radiographs), family study and pedigree analysis. Phenotypic characteristics of impacted third molar tooth in our family case report was: Severe horizontal impaction of the mandibular right third molar, Angular impaction of the maxillary right third molar and angular impaction of the maxillary left third molar, Angular impaction of the mandibular left third molar and partial eruption of the maxillary right third molar, Horizontal impaction of the mandibular left third molar and Angular impaction of the mandibular left third molar. The inheritance mode of the impacted third molar tooth in the family case report was: from mother to both daughters’ transmission, from mother to both sons’ transmission, and from mother to daughter transmission. Family study and pedigree analysis are very important for illustrate the genetic basis of impacted teeth.

Auditory aura was the very important clinical character in familial temporal Lobe epilepsy. LGI1 was the main pathogenic gene. The inheritance mode of this disease was autosomal dominant. We describes the clinical characters and gene detection in 7 patients in a temporal lobe epilepsy family with auditory aura. All patients in this family were diagnosed as temporal lobe epilepsy and had the same mutation: the splice site mutation in No. 2 base of the intron after the first exon in gene LGI1, c.215+2T>A, which induced the abnormal expression of peptide protein after the No. 71 amino acid encoded by LGI1. Some of the antiepileptic drugs, such as carbamazepine, oxcarbazepine, could be effective.

Nilaparvata lugens Stal (Hemiptera: Delphacidae) is an important agricultural insect pest all around the world due to its serious damage to rice plants by sucking sap and transmitting viral diseases. The synthetic insecticides such as neonicotinoid insecticides have widely been used to control this insect pest. Nitenpyram belongs to this group of insecticides, which is the third commercialized nicotinic acetylcholine receptor (nAChR) competitive modulators. Due to the intensive application of this insecticide, moderate level of resistance to nitenpyram has rapidly evolved in field populations of N. lugens in China. Thus, a study of the mode of inheritance and the realized heritability of resistance in laboratory-selected resistance strain against nitenpyram (resistance ratio, RR = 144.7-fold) was made to estimate the resistance in N. lugens. In this study, the reciprocal crosses were used to determine the inheritance mode. The chi-square ( χ 2 ) test and concentration-response curve goodness-of-fit between observed and the expected mortality were used to estimate monogenic resistance or multiple-gene resistance. The value of the realized heritability (h2) was 0.12 in the nitenpyram-selected strain of N. lugens. The LC50s of F1 (NR♂ × NS♀) and F1’ (NR♀ × NS♂) were 2.62 mg/L and 2.94 mg/L, respectively, with overlapped the confidence intervals of both suggesting autosomal inheritance. The degree of dominance (D) values of F1 and F1’ was 0.06 and 0.10, respectively, indicating that nitenpyram resistance was compatible with an incompletely dominant inheritance in the tested populations of N. lugens. The resistance against nitenpyram could be controlled by more than one gene in N. lugens. The present study suggested that nitenpyram resistance agaisnt N. lugens was inherited as autosomal, incompletely dominant and multigene. Based on the results of this study, minimize the selection for resistance may delay the evolution of resistance against nitenpyram in this species. Therefore, this study will support helpful information to manage the evolution of N. lugens resistance against nitenpyram and ensure rice food security as well as rural livelihoods.