Single and Mitochondrial Gene Inheritance Disorder Prediction Using Machine Learning

One of the most difficult jobs in the post-genomic age is identifying a genetic disease from a massive amount of genetic data.Furthermore,the complicated genetic disease has a very diverse genotype,making it challenging to find genetic markers.This is a challenging process since it must be completed effectively and efficiently.This research article focuses largely on which patients are more likely to have a genetic disorder based on numerous medical parameters.Using the patient’s medical history,we used a genetic disease prediction algorithm that predicts if the patient is likely to be diagnosed with a genetic disorder.To predict and categorize the patient with a genetic disease,we utilize several deep and machine learning techniques such as Artificial neural network(ANN),K-nearest neighbors(KNN),and Support vector machine(SVM).To enhance the accuracy of predicting the genetic disease in any patient,a highly efficient approach was utilized to control how the model can be used.To predict genetic disease,deep and machine learning approaches are performed.The most productive tool model provides more precise efficiency.The simulation results demonstrate that by using the proposed model with the ANN,we achieve the highest model performance of 85.7%,84.9%,84.3%accuracy of training,testing and validation respectively.This approach will undoubtedly transform genetic disorder prediction and give a real competitive strategy to save patients’lives.

Rice Mitochondrial Genes Are Transcribed by Multiple Promoters That Are Highly Diverged

Plant mitochondrial genes are often transcribed into complex sets of mRNA. To characterize the transcription initiation and promoter structure, the transcript termini of four mitochondrial genes, atpl, atp6, cob, rps7, in rice （Oryza sativa L.）, were determined by using a modified circularized RNA reverse transcription- polymerase chain reaction method. The results revealed that three genes （atp1, atp6, rps7） were transcribed from multiple initiation sites, indicating the presence of multiple promoters. Two transcription termination sites were detected in three genes （atp6, cob, rps7）, respectively. Analysis on the promoter architecture showed that the YRTA （Y=T or C, R=A or G） motifs that are widely present in the mitochondrlal promoters of other monocot and dicot plant species were detected only in two of the 12 analyzed promoters. Our data suggest that the promoter sequences in the rice mitochondrial genome are highly diverged in comparison to those in other plants, and the YRTA motif is not an essential element for the promoter activity.

Allotopic expression of mitochondrial genes:Basic strategy and progress

Allotopic expression of mitochondrial genes is a deliberate functional relocation of mitochondrial genes into the nucleus followed by import of the gene-encoded polypeptide from the cytoplasm into the mitochondria.For successful allotopic expression of a mitochondrial gene,several key aspects must be considered.These include the different codon dictionary used by the mitochondrial and nuclear genomes,different codon preferences between mitochondrial and nuclear-cytosolic translation systems,and the provision of an import signal to ensure that the newly translated protein in the cytosol is successfully imported into mitochondria.The allotopic expression strategy was first developed in yeast,a useful model organism for studying human and other eukaryotic cells.Currently,a number of mitochondrial genes have been successfully recoded and nuclearly expressed in yeast and human cells.In addition to its use in evolutionary and molecular biology studies,the allotopic expression strategy has been developed as a potential approach to treat mitochondrial genetic disorders.Substantial progress has been recently achieved,and the development of this technique for therapy of the mitochondrial disease Leber’s hereditary optic neuropathy(LHON)has entered phase III clinical trials.However,a number of challenges remain to be overcome to accelerate the successful application of this technique.These include improvement of nuclear gene expression,import into mitochondria,processing,and functional integration of the allotopically expressed polypeptides into mitochondrial protein complexes.This review discusses the current basic strategy,progress,challenges,and prospects of the allotopic expression strategy for mitochondrial genes.

Assembly and phylogenomic analysis of cotton mitochondrial genomes provide insights into the history of cotton evolution

Cotton is a major crop that provides the most important renewable textile fibers in the world.Studies of the taxonomy and evolution of cotton species have received wide attentions,not only due to cotton’s economic value but also due to the fact that Gossypium is an ideal model system to study the origin,evolution,and cultivation of polyploid species.Previous studies suggested the involvement of mitochondrial genome editing sites and copy number as well as mitochondrial functions in cotton fiber elongation.Whereas,with only a few mitogenomes assembled in the cotton genus Gossypium,our knowledge about their roles in cotton evolution and speciation is still scarce.To close this gap,here we assembled 20 mitogenomes from 15 cotton species spanning all the cotton clades(A–G,K,and AD genomes)and 5 cotton relatives using short and long sequencing reads.Systematic analyses uncovered a high level of mitochondrial gene sequence conservation,abundant sequence repeats and many insertions of foreign sequences,as well as extensive structural variations in cotton mitogenomes.The sequence repeats and foreign sequences caused significant mitogenome size inflation in Gossypium and its close relative Kokia in general,while there is no significant difference between the lint and fuzz cotton mitogenomes in terms of gene content,RNA editing,and gene expression level.Interestingly,we further revealed the specific presence and expression of two novel mitochondrial open reading frames(ORFs)in lint-fiber cotton species.Finally,these structural features and novel ORFs help us gain valuable insights into the history of cotton evolution and polyploidization and the origin of species producing long lint fibers from a mitogenomic perspective.

Genomic Analysis of Mitochondrial Carrier Genes in the Bombyx mori

This study is performed to investigate the mitochondrial carrier gene family in silkworm genome. In total, 30 genes are identified and claded into eight well-conserved groups. Gene duplication contributes to the expansion and complexity of this family. Diverse expression patterns suggest their functional differentiation. Analyses of the sitespecific profiles reveal critical amino acid residues for functional divergence. This study highlights the molecular evolution of the mitochondrial carrier gene family in silkworm and may provide a starting point for further experimental verification.

Genetic Differences of Mitten Crabs Based on RFLP Analysis on Mitochondrial Cytochrome Oxidase Subunit I(COI) Gene

The genetic differences of 15 mitten crab populations from 6 river systems in China's Mainland and 1 population from Russia were studied based on RFLP analysis of mitochondrial cytochrome oxidase subunit I （CO I）. The results showed that Tas I-RFLP pattern could be used as a genetic marker to distinguish Eriocheir hepuensis from Eriocheir sinensis, Eriocheirjaponica and Eriocheir leptognathus; genetic distances among 13 populations of Eriocheir sinensis range from 0 to 0.015, indicating that they were different geographic strains; the subspecies status of Eriocheir sinensis and Eriocheir hepuensis （population from Nanliujiang） were considered owning to their genetic distances of 0.02-0.044, indicating that genetic divergence between them was low; Eriocheir leptognathus （population from Nanpaihe, Tianjin） was the most distant taxon with genetic distances value of 0.147-0.195, which could be defined as genetic distances between species in genus Eriocheir.

The Genetic Structure and Diversity of Repomucenus curvicornis Inhabiting Liaoning Coast Based on Mitochondrial COⅠ Gene and Control Region

[Object] This study was conducted to explore the genetic diversity and structure of the wild Repomucenus curvicornis inhabiting Liaoning Coast, China. [Method] The mitochondrial COⅠ gene and control region（CR） were PCR amplified from the wild R. curvicornis populations from the Liaodong Bay（n=22） and the northern Yellow Sea（n=18）, sequenced and analyzed for genetic diversity. [Result] The contents of A, T, C and G of 624 bp COⅠ gene were 24.09%, 31.04%, 25.28%, and 19.59%, and those of 460 bp CR fragment were 32.96%, 32.80%, 14.86% and 19.38%, respectively. The total number of variable sites, average number of nucleotide differences（ k）, haplotype diversity（H） and nucleotide diversity（π） based on COⅠ gene were 38, 4.67,（0.96±0.02） and（0.007 5±0.004 2）, and those based on CR fragment were 26, 3.35,（0.97 ±0.02） and（0.007 3±0.004 3）, respectively. Based on mitochondrial COⅠ gene and CR, the genetic diversity of Liaodong Bay population was lower than that of the northern Yellow Sea population. The AMOVA analysis based on CR fragments revealed almost significant genetic divergence between the Liaodong Bay and the northern Yellow Sea populations, while there was no significant genetic divergence based on COⅠ gene. The results showed that CR and COⅠ gene are effective molecular markers for detecting the genetic diversity of R. curvicornis population, while CR is more reliable than COⅠ gene in detecting the genetic structure. [Conclusion] CR is an appropriate marker for genetic analysis of marine fish population.

Phylogenetic Analyses Reveal a Unique Species of Elaphe(Serpentes,Colubridae)New to Science

The snakes comprising the monophyletic group referred to as ratsnakes are found throughout Asia,Europe and the New World.Recently,three snake samples likely belonging to the ratsnakes were collected in Zoige County,Sichuan Province,China.Species identity was difficult to delimit morphologically because the specimens were juveniles and partially damaged.Subsequently,a molecular phylogenetic approach was used.Portions of three mitochondrial genes(cyt b,ND4 and 12S rRNA) were sequenced and analyzed.The results showed that they were sister to the genus Elaphe.Very little genetic variation was found among the three samples.The minimum genetic distances between these samples and those within Elaphe were greater than any currently recognized species within the genus.We conclude that this likely represents a new species within the genus Elaphe.Adult specimens and a morphologic description are needed for further study.

Interspecies Phylogenetic Analysis of Clonorchis sinensis in High-incidence Areas of Hunan Province, China

Objective This study aims to investigate the infection of Clonorchis sinensis(C.sinensis)in highincidence areas of Hunan Province,China.The phylogenetic analysis of the C.sinensis species in the highly infected areas was carried out.Method Infection of the definitive human host and intermediate fish host by C.sinensis was investigated,and the mitochondrial genes cox1 and Nad1 were used as genetic markers for phylogenetic analysis.Results In 2016–2020,the average population infection rate of Hunan was 1.38%,while in Tongdao County the rate was up to 26.90%,and the highest fish infection rate was detected in Qiyang County(99.44%in the dorsal fin of crucian carp).High genetic sequence similarity was observed in the samples from Qiyang and Lengshuitan which exhibited high homology with those from Guangdong and Gansu,whereas the parasitic species from Tongdao was highly homologous with those located in high-latitude areas.Moreover,no significant difference was found in the gene sequence of the parasitic species in definitive hosts dogs and cats.Conclusion The systematically study of C.sinensis infection in the high-incidence areas will contribute greatly to the prevention and effectively controlling the spread of Clonorchis sinensis in Hunan Province The endemic of C.sinensis infection in Hunan Province is the result of co-action of local and foreign parasite species.

Low Genetic Polymorphism at the Cytochrome C Oxidase I in Silkworm Strains of the Brazilian Germplasm Bank

Nucleotide sequences have been used to distinguish species and specimens for many years. More recently, the use of a partial sequence of 650 bp of the cytochrome c oxidase I, COI mitochondrial gene, has been proposed for species identification, known as DNA barcodes. In this work, a short sequence of the DNA barcode is described—approximately 250 bp, named as “DNA mini-barcode”—to molecularly identify different silkworm strains maintained at the unique public Germplasm Bank of Bombyx mori, at the Universidade Estadual de Maringá, UEM, Brazil. Analysis revealed no significant differences among the silkworm strains. The phylogenetic tree obtained by the neighbor-joining method and K2P distance, in which specimens of B. mandarina were used as outgroup, clustered all the specimens of B. mori in a unique clade. Genetic variability detect within B. mori was low or nonexistent. In conclusion, the partial region of 250 bp of the mitochondrial gene COI herein analyzed may not be efficient to discriminate silkworm strains from the UEM Germplasm Bank of Bombyx mori.

Cryptic species composition and genetic diversity within Bemisia tabaci complex in soybean in India revealed by mtCOI DNA sequence

Bemisia tabaci is a cryptic species complex, causing signiifcant loss on many agricultural y important crops worldwide. Knowledge on species composition and diversity within B. tabaci complex is critical for evolving sustainable pest management strategies. Here we investigate the whitelfy species complex in soybean in major soybean growing states of India. The mitochondrial cytochrome oxidase gene subunit-1 (mtCOI) based phylogenetic relationships established using Bayesian methods indicated the existence of three cryptic species namely Asia I, Asia II 1, and Asia II 7. Al the haplotypes detected in the study could be assigned to these three cryptic species fol owing the species demarcation criteria of 3.5%divergence threshold. Of these, Asia II 1 was found to be predominant with wide spread distribution across the surveyed regions from cool temperate zones to hot and humid tropical plains. On the contrary, cryptic species Asia II 7 showed localized distribu-tion. The Asia II 1 exhibited the highest haplotype diversity and Asia I showed high level of nucleotide diversity. There was a signiifcantly high genetic differentiation among these three cryptic species. The MEAM 1, a dreadful invasive species was not detected in the specimens tested in the current study. The diversity and distribution of three cryptic species is discussed in the light of current knowledge on distribution of whitelfy species in India and yel ow mosaic disease observed during sampling survey.

A single degenerated primer significantly improves COX1 barcoding performance in soil nematode community profiling

A new COX1 primer for soil nematode metabarcoding was designed,and this primer outperforms other commonly used COX1 primer pairs in species recovery and quantity of PCR products.•The lack of reference database is the main reason that led to the low species recovery in COX1 metabarcoding.•We expanded current NCBI database by adding 51 newly generated COX1 reference sequences.Microscopic nematodes play important roles in soil ecosystems and often serve as bioindicators of soil health.The identification of soil nematodes is often difficult due to their limited diagnostic characters and high phenotypic plasticity.DNA barcoding and metabarcoding techniques are promising but lack universal primers,especially for mitochondrial COX1 gene.In this study a degenerated COX1 forward primer COIFGED was developed.The primer pair(COIFGED/JB5GED)outperforms other four commonly used COX1 primer pairs in species recovery and quantity of polymerase chain reaction(PCR)products.In metabarcoding analysis,the reads obtained from the new primer pair had the highest sequencing saturation threshold and amplicon sequence variant(ASV)diversity in comparison to other COX1 as well as 18S rRNA primers.The annotation of ASVs suggested the new primer pair initially recovered 9 and 6 out of 25 genera from mock communities,respectively,outperformed other COX1 primers,but underperformed the widely used 18S NF1/18Sr2b primers(16 out of 25 genera).By supplementing the COX1 database with our reference sequences,we recovered an additional 6 mock community species bringing the tally closer to that obtained with 18S primers.In summary,our newly designed COX1 primers significantly improved species recovery and thus can be supplementary or alternative to the conventional 18S metabarcoding.

Relationship between mutations of mitochondrial DNA ND1 gene and type 2 diabetes

Background Recent studies have indicated that many mutations in mitochondrial (mt)DNA NDI gene region are related to diabetes mellitus. In this study we explored the relationship between various mtDNA ND1 gene mutations and type 2 diabetes mellitus (DM) among Chinese. Methods Using PCR restriction fragment length polymorphism (PCR-RFLP) analysis and gene sequencing, 4 spots of mtDNA (nt3243, nt3316, nt3394, nt3426) were screened in 478 diabetics and 430 non-diabetic subjects.Results In diabetic group, there were 13 carriers (2.72%)of 3316 G→A mutation,12 (2.51%) of 3394 T→C mutation and 2 (0.42%) of 3426A→G mutation. In controls, only 3394 T→C mutation was observed in 2 subjects (0.47%). There was significant difference in the frequency of 3316 and 3394 mutation between two groups (P<0.05, respectively). More subjects with mitochondrial DNA ND1 gene mutations had DM family history and greater tendency of maternal inheritance when compared to those patients without mutation in diabetic group(P<0.01). A 3426 mutation diabetic pedigree was studied, and we found 12 maternal members in the family had the same mutation. Conclusion mtDNA ND1 gene mutations at nt3316 (G→A), nt3394 (T→C) and 3426 (A→G) might contribute to the pathogenesis of DM with other genetic factors and environment factors.

Phylomitogenomics of Malacostraca(Arthropoda: Crustacea)

Along with the sequencing technology development and continual enthusiasm of researchers on the mitochondrial genomes, the number of metazoan mitochondrial genomes reported has a tremendous growth in the past decades. Phylomitogenomics—reconstruction of phylogenetic relationships based on mitochondrial genomic data—is now possible across large animal groups. Crustaceans in the class Malacostraca display a high diversity of body forms and include large number of ecologically and commercially important species. In this study, comprehensive and systematic analyses of the phylogenetic relationships within Malacostraca were conducted based on 86 mitochondrial genomes available from Gen Bank. Among 86 malacostracan mitochondrial genomes, 54 species have identical major gene arrangement（excluding t RNAs） to pancrustacean ground pattern,including six species from Stomatopoda, three species from Amphipoda, two krill, seven species from Dendrobranchiata（Decapoda）, and 36 species from Pleocyemata（Decapoda）. However, the other 32 mitochondrial genomes reported exhibit major gene rearrangements. Phylogenies based on Bayesian analyses of nucleotide sequences of the protein-coding genes produced a robust tree with 100% posterior probability at almost all nodes. The results indicate that Amphipoda and Isopoda cluster together（Edriophthalma）（BPP=100）.Phylomitogenomic analyses strong support that Euphausiacea is nested within Decapoda, and closely related to Dendrobranchiata, which is also consistent with the evidence from developmental biology. Yet the taxonomic sampling of mitochondrial genome from Malacostraca is very biased to the order Decapoda, with no complete mitochondrial genomes reported from 11 of the 16 orders. Future researches on sequencing the mitochondrial genomes from a wide variety of malacostracans are necessary to further elucidate the phylogeny of this important group of animals. With the increase in mitochondrial genomes available, phylomitogenomics will emerge as an important component in the Tree of Life researches.

Clinical,pathological and genetic study of a kindred of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes

The first description of a syndrome including stroke-like episodes, lactic acidaemia, and ragged red fibres, was reported by Shapira et al in 1975. 1 Pavlakis et al 2 described further cases, introduced the acronym MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes), and suggested that this represented a distinct mitochondrial disease phenotype. In 1990, Goto et al 3 identified A3243G mutation in the transfer RNA (tRNA) leucine (UUR) gene in some patients with MELAS. Although this mutation has now been established to be the commonest mtDNA defect it is often misdiagnosed. Here we report a kindred of MELAS including a mother and a son. Clinical, pathological and genetic studies are proceeding.

Invasion history of Solenopsis invicta （Hymenoptera： Formicidae） in Fujian, China based on mitochondrial DNA and its implications in development of a control strategy

One of the most invasive species worldwide, Solenopsis invicta Buren, has been described in China since 2003. Recent studies have suggested that China populations are the result of introductions from the USA; however, detailed molecular studies need to be performed in order to understand the expansion and potential multiple introductions from other countries into China. As there were populations of red imported fire ant, S. invicta in different areas and with different methods of introduction, mitochondrial cytochrome oxidase Ⅰ gene was used as a marker from 12 populations in four cities in Fujian Province, China, to determine the relationship of invasion among these populations. The three most common haplotypes previously describe in invasive populations of S. invicta： H5, H22 and H36, were found in Fujian. However, frequencies in each city were different. For instance, three populations from Longyan city which invaded with waste plastics, shared haplotype H5. Populations from Xiamen city and Jinjiang city which dispersed with nursery stock, sward and scrap leather, shared haplotype H22. The population from Nanyan village of Xinluo district, Longyan city, bore haplotype H36. Mitochondrial data reveals that the invasion history of S. invicta in Fujian Province is complex, including multiple invasions probably from other provinces within China. Security measures to prevent S. invicta spreading within China are as important as from overseas.

Phylogeny of the green lacewing Chrysoperla nipponensis species-complex （Neuroptera： Chrysopidae）in China, based on mitochondrial sequences and AFLP data

Severalstudieshaveindicatedthatthegreenlacewing, Chrysoperlanipponensis （Neuroptera： Chrysopidae） may include more than one valid species. We investigated the phylogenetic status of Chrysoperla nipponensis s.l. in China and Japan using mitochondrial sequences and AFLP data. The molecular phylogenetic analyses based on mitochondrial genes showed that the C. nipponensis species-complex comprises four clades, each having high support values. In addition, the phylogenetic tree based on AFLP data indicates that the species-complex comprises three groups. These results confirm that C. nipponensis s.1. comprises at least three genetically distinct clades and suggests that two of these clades may be closely related to populations of C. nipponensis in Japan. However, these clades cannot be recognized as species until analysis of their courtshin songs has been cornnleted

Advances in cochlear implantation for hereditary deafness caused by common mutations in deafness genes

The pathogenic factors of deafness are complex;more than 50%of cases are caused by genetic factors.Between 75%and 80%of cases of hereditary hearing impairment are autosomal recessive,15%to 25%are autosomal dominant,and 1%to 2%are mitochondrial or X-linked.Cochlea implantation is the main method for treating severe and extremely severe bilateral sensorineural deafness and it is widely used in clinical treatment.As clinical cases of cochlea implantation accumulate,differences in the efficacy of implantation in individuals are emerging and attracting attention.In addition to residual hearing level,implantation age,and other factors,gene mutation is an important factor influencing postoperative rehabilitation in patients.With continuous progress in genetic testing technology for deafness,genetic diagnosis has become an important tool in preoperative evaluation and postoperative effect prediction in patients undergoing cochlear implantation.This article reviews the current status and future development of cochlear implantation in the treatment of hereditary deafness resulting from mutations in common deafness-causing genes.

Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome

Background Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients. Methods Sixty-five unrelated cases （35 men and 30 women） who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography （CT） scan or magnetic resonance imaging （MRI）. The differential diagnosis of organic acidurias and fatty acid IS-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA （T8993G, T8993C, T9176C, A8344G, A3243G） were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 （26.2%） of the patients. The diagnosis was confirmed by autopsy in 6 （9.2%） patients. Results The patients had various forms of metabolic encephalomyopathy. Filly-nine （90.8%） of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty （30.8%） patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases （7.7%）. Of these, the A8344G mutation was detected in 2 patients. The T8993G T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 （12.3%） families by DNA sequencing. A G604C mutation was identified in 6 （9.2%） patients. The genotypes of 52 patients remained unknown. Conclusions Leigh syndrome presents as a diverse array of clinical features and can result from specific mutations in nuclear or mitochondrial DNA. In this study, SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 （12.3%） out of 65 patients with Leigh syndrome. It indicates that SURF1 mutations might be a common cause of Leigh syndrome in China. The etiology of Leigh syndrome in Chinese patients represents a persistent challenge to clinicians.