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1.
Zool Res ; 42(5): 660-665, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34472227

RESUMO

Flatheads are valuable commercial fish species endemic to the Indo-West Pacific. Due to their economic value and unique biological traits, such as metamorphosis and camouflage, they serve as ideal marine organisms for studies on demersal adaptation and evolution. The brown-spotted flathead (Platycephalus sp.1) is the most widely distributed in the northwestern Pacific. Despite the lack of a valid scientific name, it has been long recognized and exploited in the marine fisheries of China, Japan, and Korea. In the current study, we applied Illumina, PacBio, and Hi-C sequencing to assemble a chromosome-scale genome for this species. The assembled genome was 660.63 Mb long with a scaffold N50 of 28.65 Mb and 100% of the contigs were anchored onto 24 chromosomes. We predicted 22 743 protein-coding genes, 94.8% of which were functionally annotated. Comparative genomic analyses suggested that Platycephalus sp.1 diverged from its common ancestor with Gasterosteus aculeatus ~88.4 million years ago. The expanded gene families were significantly enriched in immune, biosynthetic, and metabolic pathways. Furthermore, three shared Gene Ontology terms and 377 common positively selected genes were identified between flathead and flatfish species, suggesting that these genes may contribute to demersal adaptation in flatheads. The assembled genomic data provide a valuable molecular resource for further research on the biological and adaptive evolution of flathead species.


Assuntos
Adaptação Fisiológica/genética , Cromossomos/genética , Peixes/genética , Genoma , Genômica/métodos , Animais , Oceano Pacífico , Filogenia
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 829-832, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487523

RESUMO

OBJECTIVE: To detect variants of NF1 gene among thirteen patients with neurofibromatosis type 1. METHODS: Genomic DNA was extracted from peripheral blood samples of the patients. High-throughput sequencing was employed to detect potential variants of the NF1 and NF2 genes. RESULTS: Thirteen pathogenic variants were identified among the patients, which included one NF1 deletion, three missense variants, three nonsense variants and six frameshifting variants. Among these, 10 variants have been associated with neurofibromatosis type 1. c.4180A>T (p.Asn1394Tyr), c.4217dupT (p.Leu1406fs) and c.1753dupT(p.Leu585Phefs*3) were unreported previously. Based on the guidelines of the American College of Medical Genetics and Genomics, c.4180A>T (p.Asn1394Tyr) was predicted to be likely pathogenic (PS2+PM1+PM2+PP2), while c.4217dupT (p.Leu1406fs) and c.1753dupT (p.Leu585Phefs*3) were predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION: Variants of the NF1 gene probably underlay the disease among these children. Above findings have enriched the the spectrum of NF1 gene variants.


Assuntos
Genes da Neurofibromatose 1 , Neurofibromatose 1 , Criança , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Neurofibromatose 1/genética
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 838-840, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487525

RESUMO

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with resistance to thyroid hormone syndrome (RTH). METHODS: Exons 7 to 10 of the THRbeta gene were sequenced for the proband and members of his pedigree. RESULTS: Three patients from the pedigree were identified. All have presented with palpitation, fatigue, goiter, elevated free thyroid hormone and free triiodothyronine, and normal or elevated thyrotropin. Genetic testing revealed that the proband, his mother, second sister and one of her daughters had carried a heterozygous c.1336T>A variant of the THRbeta gene, which resulted in substitution of Cysteine by Serine at position 446. The variant was unreported previously. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.1336T>A(p.Cys446Ser) variant of THRbeta gene was predicted to be lilely pathogenic(PM1+PM2+PM5+PP3). CONCLUSION: The c.1336T>A variant, identified in the exon 10 of the THRbeta gene, probably underlay the RTH in this pedigree. Genetic testing has validated the clinical diagnosis for this pedigree.


Assuntos
Genômica , Mães , Feminino , Heterozigoto , Humanos , Mutação , Linhagem
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 877-879, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487535

RESUMO

OBJECTIVE: To explore the genetic basis for a patient diagnosed with tuberous sclerosis complex (TSC). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out to detect potential variant, and the result was verified by Sanger sequencing. RESULTS: The patient was found to harbor a heterozygous c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene. The same variant was not found in his unaffected parents and 100 unrelated healthy controls. Based on the American College of Medical Genetics and Genomics guidelines, the variant was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION: The novel c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene probably underlay the TSC in this patient.


Assuntos
Esclerose Tuberosa , Genômica , Heterozigoto , Humanos , Mutação , Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 887-890, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487538

RESUMO

OBJECTIVE: To explore the clinical features and disease-causing variants of a pediatric patient with fatal encephalopathy caused by mitochondrial peroxidase division deficiency, to identify the possible genetic causes of the disease and provide a basis for clinical diagnosis. METHODS: A child with fatal encephalopathy caused by mitochondrial peroxidase division deficiency in West China Second Hospital of Sichuan University was selected. The clinical manifestations, laboratory findings and disease-causing variant were analyzed. RESULTS: The main clinical symptoms of the patient were fever, headache and vomiting, followed by drug refractory epilepsy and progressive disturbance of consciousness. MRI showed deepening of sulcus, dilatation of bilateral ventricles, and multiple patch-like abnormal signals in paraventricular white matter, semioval center and subcortical white matter of bilateral frontal lobe. Gene detection showed a heterozygous missense variant c.1207C>T(p.Arg403Cys) in DNM1L, according to the American College of Medical Genetics and Genomics classification standards and guidelines for genetic variants, this variant was predicted to be pathogenic(PS1+PS2+PM2+PP3). After treated with gamma globulin, glucocorticoid, "mitochondrial cocktail therapy" and anti-epilepsy drugs, the condition of the patient was getting better, seizure attacks reduced and consciousness level improved. CONCLUSION: The c.1207C>T variant in DNM1L gene may be the disease-causing variant for the patient, and the result of genetic testing provides a basis for the clinical diagnosis in this case.


Assuntos
Epilepsia Resistente a Medicamentos , Peroxidase , Criança , Dinaminas , Genômica , Humanos , Mitocôndrias , Mutação , Convulsões
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 891-894, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487539

RESUMO

OBJECTIVE: To explore the genetic basis for a juvenile with maturity-onset diabetes of the young type 12(MODY12). METHODS: High-throughput sequencing was carried out to screen for the variants. Candidate variant was verified by Sanger sequencing. Pathogenity of the variant was predicted by searching the genetic databases and analysis by using bioinformatic software. RESULTS: Genetic testing indicated that the patient and his mother have both carried a heterozygous c.3976G>A variant (p.Glu1326Lys) in exon 32 of the ABCC8 gene. Prediction of the protein structure suggested the variant to be deleterious. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be uncertain significance. CONCLUSION: Whether the c.3976G>A variant of the ABCC8 gene is the cause of the disease in this patient or not depends on the functional studies and more case data. Above finding has enriched the spectrum of ABCC8 gene variants.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/genética , Testes Genéticos , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
7.
Curr Protoc ; 1(9): e252, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34506690

RESUMO

The creation of visualizations to interpret genomics data remains an important aspect of data science within computational biology. The GenVisR Bioconductor package was created to lower the entry point for publication-quality graphics and has remained a popular suite of tools within this domain. GenVisR supports visualizations covering a breadth of topics including functions to produce visual summaries of copy-number alterations, somatic variants, sequence quality metrics, and more. Recently, the GenVisR package has undergone significant updates to increase performance and functionality. To demonstrate the utility of GenVisR, we present protocols for use of the updated Waterfall() function to create a customizable Oncoprint-style plot of the mutational landscape of a tumor cohort. We explain the basics of installation, data import, configuration, plotting, clinical annotation, and customization. A companion online workshop describing the GenVisR library, Waterfall() function, and other genomic visualization tools is available at genviz.org. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Generating a Waterfall() plot from original mutation data Basic Protocol 2: Adding clinical data to a Waterfall() plot Basic Protocol 3: Customizing mutation burden in Waterfall() plots Basic Protocol 4: Brief exploration of customizable options Support Protocol 1: Installing GenVisR.


Assuntos
Neoplasias , Software , Biologia Computacional , Genoma , Genômica , Humanos , Neoplasias/genética
8.
BMC Bioinformatics ; 22(1): 434, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507532

RESUMO

BACKGROUND: One of the major challenges in precision medicine is accurate prediction of individual patient's response to drugs. A great number of computational methods have been developed to predict compounds activity using genomic profiles or chemical structures, but more exploration is yet to be done to combine genetic mutation, gene expression, and cheminformatics in one machine learning model. RESULTS: We presented here a novel deep-learning model that integrates gene expression, genetic mutation, and chemical structure of compounds in a multi-task convolutional architecture. We applied our model to the Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) datasets. We selected relevant cancer-related genes based on oncology genetics database and L1000 landmark genes, and used their expression and mutations as genomic features in model training. We obtain the cheminformatics features for compounds from PubChem or ChEMBL. Our finding is that combining gene expression, genetic mutation, and cheminformatics features greatly enhances the predictive performance. CONCLUSION: We implemented an extended Graph Neural Network for molecular graphs and Convolutional Neural Network for gene features. With the employment of multi-tasking and self-attention functions to monitor the similarity between compounds, our model outperforms recently published methods using the same training and testing datasets.


Assuntos
Antineoplásicos , Aprendizado Profundo , Neoplasias , Preparações Farmacêuticas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Genômica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética
9.
Rev Peru Med Exp Salud Publica ; 38(2): 267-271, 2021.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-34468574

RESUMO

The understanding of COVID-19, caused by the SARS-CoV-2, is essential to improve evidence-based public health policies. The effective reproductive number (Rt) in Peru was estimated using information from 113 complete genomes sequenced by the Instituto Nacional de Salud del Perú (INS), available in the GISAID public database. The Rt trend during March and April of 2020 was found to be similar to results from other epidemiological reports. The Rt decreased during the first two weeks of March. Its lowest value was reported during the week after the quarantine began. The Rt increased moderately after the second week of April. The implication of early decisions taken to mitigate the transmission are discussed. Genomic surveillance will be necessary to understand the transmission and evolution of SARS-CoV-2 in Peru, and will complement the epidemiological information.


Assuntos
COVID-19 , SARS-CoV-2 , Número Básico de Reprodução , Genômica , Humanos , Peru
10.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2703-2718, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472290

RESUMO

Plants with alien genomic components (alien chromosomes / chromosomal fragments / genes) are important materials for genomic research and crop improvement. To date, four strategies based on trait observation, chromosome analysis, specific proteins, and DNA sequences have been developed for the identification of alien genomic components. Among them, DNA sequence-based molecular markers are mainly used to identify alien genomic components. This review summarized several molecular markers for identification of alien genomic components in wheat, cabbage and other important crops. We also compared the characteristics of nine common molecular markers, such as simple sequence repeat (SSR), insertion-deletion (InDel) and single nucleotide polymorphism (SNP). In general, the accuracy of using a combination of different identification methods is higher than using a single identification method. We analyzed the application of different combination of identification methods, and provided the best combination for wheat, brassica and other crops. High-throughput detection can be easily achieved by using the new generation molecular markers such as InDel and SNP, which can be used to determine the precise localization of alien introgression genes. To increase the identification efficiency, other new identification methods, such as microarray comparative genomic hybridization (array-CGH) and suppression subtractive hybridization (SSH), may also be included.


Assuntos
Cromossomos de Plantas , Genoma de Planta , Hibridização Genômica Comparativa , Genoma de Planta/genética , Genômica , Triticum/genética
11.
Adv Exp Med Biol ; 1325: 151-171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495534

RESUMO

Although changes in protein glycosylation are observed in a wide range of diseases and pathological states, the examples of use of glycans as biomarkers and therapeutic targets are limited. This is not in small part because the understanding of human glycome regulation in vivo is incomplete and fragmented. Combination of human glycomics and genomics offers a powerful "data-driven hypotheses" approach to dissect the complex human glycobiology in vivo in an agnostic manner.In this chapter we review a decade of quantitative genetic studies of human N-glycome, including studies of its heritability and gene-mapping via genome-wide association studies (GWASs). We show that GWASs of human N-glycome start revealing regulators of the biochemical network of N-glycosylation. Some of these regulators demonstrate pleiotropic effects on human disease, especially autoimmune and inflammatory. We emphasize the use of in silico functional methods and multi-omics approaches to prioritize functional mechanisms to be further validated in laboratory experiments. This combined approach will lead to better understanding of mechanisms of regulation of human protein glycosylation and will provide a rich source of etiologic insight, therapeutic interventions, and biomarkers.


Assuntos
Estudo de Associação Genômica Ampla , Glicômica , Genômica , Glicosilação , Humanos , Polissacarídeos
12.
Rinsho Ketsueki ; 62(8): 1004-1011, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497186

RESUMO

Precision medicine refers to a medical model wherein treatments are customized for the patients according to their lifestyles, genetic background, and other molecular and physiological test results. Herein, I discuss the utility of comprehensive genomic profiling of hematologic malignancies and provide a perspective on the future of genomics-based precision medicine in the field of hematology/oncology.


Assuntos
Hematologia , Neoplasias , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Medicina de Precisão
13.
Rinsho Ketsueki ; 62(8): 1038-1049, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497190

RESUMO

Myelodysplastic syndrome (MDS) is a group of clonal diseases caused by the accumulation of genetic mutations. The outcome of MDS extremely varies, with an overall survival ranging from just a few months to years. Therefore, accurate classification and prognostic scoring are essential. Patients with MDS are generally divided into two risk groups. For low-risk patients, the treatment goal is to improve ineffective hematopoiesis and quality of life. Meanwhile, in high-risk patients, treatment aims to extend survival and prevent progression to leukemia. To date, different guidelines recommend azacytidine, which is a hypomethylating agent, as the initial treatment. This is the only therapy associated with a significant survival in high-risk patients who are not eligible for hematopoietic stem cell transplantation. However, the response rate is only about 40%, and responses are mostly transient. Recent advancements in sequencing technologies have improved our understanding of the molecular pathogenesis of MDS by identifying somatic mutations in almost each patient with MDS. The high phenotypic and clinical heterogeneity of patients with MDS is primarily based on genetics. Due to a high degree of heterogeneity, the treatment policy for patients with MDS is still challenging. In this review, we will discuss the current treatment strategies for MDS in Japan, including future perspectives.


Assuntos
Síndromes Mielodisplásicas , Qualidade de Vida , Azacitidina , Genômica , Humanos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Fatores de Risco
14.
Rinsho Ketsueki ; 62(8): 1131-1138, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497200

RESUMO

Ph-like acute lymphocytic leukemia (ALL) is a subtype of Ph-negative B precursor ALL, and its gene expression profile is similar to that of Ph+ALL. In recent decades, comprehensive genomic analyses have revealed that Ph-like ALL has two types. The first type is associated with the ABL-class tyrosine kinase fusion gene, and the second type with fusion genes involving cytokine receptors or molecules, including CRLF2, which are correlated with the activation of the JAK/STAT pathway. Based on these findings, tyrosine kinase or JAK inhibitors were found to be effective for Ph-like ALL. Genetic abnormalities identified in Ph-like ALL, except for CRLF2 rearrangement, are quite rare. Thus, functional studies regarding each genomic abnormality are relevant for establishing targeted therapies for Ph-like ALL. To develop a targeted molecular therapy, a functional study of NCOR1-LYN, which is a novel ABL-class fusion gene, was conducted on pediatric patients with Ph-like ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Genômica , Humanos , Terapia de Alvo Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Tirosina Quinases , Transcriptoma
15.
Rinsho Ketsueki ; 62(8): 967-977, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497237

RESUMO

The etiology and pathogenesis of acute myeloid leukemia (AML) have been elucidated at chromosomal and genetic levels. The classification and prognosis for its treatment has clearly involved specific chromosomal aberrations and genetic mutations. The recent comprehensive genomic analysis represented by next-generation sequencers has led to discovering new genetic mutations in AML. These findings have not only been applied clinically as prognostic factors and MRD markers but also contributed to the development of new molecular-targeting drugs. Many new drugs have already been approved in the USA and Europe, and new stratified treatments have tried to incorporate them. With the advent of venetoclax, treatment strategies, especially for patients with poor prognosis and who are unfit, have been substantially revised, and the maintenance therapy for AML is also being reevaluated in accordance to the National Comprehensive Cancer Network guidelines. This article will review the current status of AML treatment in Japan and according to Western guidelines.


Assuntos
Leucemia Mieloide Aguda , Aberrações Cromossômicas , Genômica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Prognóstico
16.
Microbiome ; 9(1): 182, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479645

RESUMO

BACKGROUND: Deep-sea animals in hydrothermal vents often form endosymbioses with chemosynthetic bacteria. Endosymbionts serve essential biochemical and ecological functions, but the prokaryotic viruses (phages) that determine their fate are unknown. RESULTS: We conducted metagenomic analysis of a deep-sea vent snail. We assembled four genome bins for Caudovirales phages that had developed dual endosymbiosis with sulphur-oxidising bacteria (SOB) and methane-oxidising bacteria (MOB). Clustered regularly interspaced short palindromic repeat (CRISPR) spacer mapping, genome comparison, and transcriptomic profiling revealed that phages Bin1, Bin2, and Bin4 infected SOB and MOB. The observation of prophages in the snail endosymbionts and expression of the phage integrase gene suggested the presence of lysogenic infection, and the expression of phage structural protein and lysozyme genes indicated active lytic infection. Furthermore, SOB and MOB appear to employ adaptive CRISPR-Cas systems to target phage DNA. Additional expressed defence systems, such as innate restriction-modification systems and dormancy-inducing toxin-antitoxin systems, may co-function and form multiple lines for anti-viral defence. To counter host defence, phages Bin1, Bin2, and Bin3 appear to have evolved anti-restriction mechanisms and expressed methyltransferase genes that potentially counterbalance host restriction activity. In addition, the high-level expression of the auxiliary metabolic genes narGH, which encode nitrate reductase subunits, may promote ATP production, thereby benefiting phage DNA packaging for replication. CONCLUSIONS: This study provides new insights into phage-bacteria interplay in intracellular environments of a deep-sea vent snail. Video Abstract.


Assuntos
Bacteriófagos , Animais , Bactérias/genética , Bacteriófagos/genética , Genômica , Proteômica , Caramujos , Transcriptoma/genética
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 849-852, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487528

RESUMO

OBJECTIVE: To explore the clinical feature and gene variant for two cases of primary male infertility caused by severe asthenospermia and to analyze the etiology of the disease. METHODS: Genomic DNA of peripheral blood samples of patients and their parents was extracted and gene variant analysis of the patients was conducted by using whole exome sequencing. Suspected pathogenic variant was verified by Sanger sequencing and pathogenic analysis. RESULTS: Whole exome sequencing showed that the DNAH1 gene of patient 1 had two heterozygous variants of c.2016T>G(p.Y672X) and c.6017T>G (p.V2006G). The DNAH1 gene of patient 2 had a homozygous variant of c.2610G>A(p.W870X), which were inherited from his father and mother, respectively. According to American College of Medical Genetics and Genomics standards and guidelines, the c.2016T>G (p.Y672X) and c.2610G>A (p.W870X) varaints of DNAH1 gene were predicted to be pathogenic (PVS1+PM2+PM3+PP3). CONCLUSION: The two patients of multiple morphological abnormalities of the sperm flagella may be caused by DNAH1 gene variant, which has resulted in primary male infertility.


Assuntos
Dineínas , Infertilidade Masculina , Cauda do Espermatozoide , Dineínas/genética , Genômica , Humanos , Infertilidade Masculina/genética , Masculino , Mutação , Cauda do Espermatozoide/patologia , Sequenciamento Completo do Exoma
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 857-860, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487530

RESUMO

OBJECTIVE: To report on a patient with congenital muscular dystrophy (CMD) due to a missense variant of LMNA gene and explore its pathogenicity. METHODS: The 1-year-and-1-month-old boy has presented with motor development delay and elevation of muscle enzymes for more than half a year. Congenital myopathy was suspected. Following muscle biopsy, HE staining, immunostaining and electron microscopy were conducted to clarify the clinical diagnosis. Meanwhile, DNA was extracted from the child and his parents' peripheral venous blood samples. Trio-whole exome sequencing (trio-WES) was carried out to detect pathogenic variant in the child. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: Both light and electron microscopy showed a large area of necrotic muscle tissues with infiltration of inflammatory cells. Immunohistochemistry revealed a large amount of muscle cells to be diffusely positive for Dysferlin. The patient's motor delays, elevations of muscle enzymes and histopathological results suggested a clinical diagnosis of CMD. A de novo missense c.1072G>A (p.E358K) variant was detected in the LMNA gene by trio-WES. The variant was unreported previously (PS2) and was absent from major allele frequency databases (PM2). It was a loss of function variant and was considered as hotspot variant in the LMNA gene (PM1) as the amino acid (E), located in position 358, was highly conserved, and change of this amino acid was found to cause destruction of the filament domain (AA: 30-386), which may result in serious damage to the intermediate filament protein. Furthermore, c.1072G>A (p. E358K) in LMNA gene was also predicted to be pathogenic based on MutationTaster, PROVEAN and PolyPhen-2 (PP3) analysis. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified to be likely pathogenic (PS2+PM1+PM2+PP3). CONCLUSION: The child's condition may be attributed to the de novo missense c.1072 G>A (p.E358K) variant of the LMNA gene. Above discovery has expanded the variant spectrum of the LMNA gene.


Assuntos
Lamina Tipo A , Distrofias Musculares , Frequência do Gene , Genômica , Humanos , Lactente , Lamina Tipo A/genética , Masculino , Distrofias Musculares/genética , Mutação , Sequenciamento Completo do Exoma
19.
BMC Genomics ; 22(1): 644, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488632

RESUMO

BACKGROUND: Inversion Symmetry is a generalization of the second Chargaff rule, stating that the count of a string of k nucleotides on a single chromosomal strand equals the count of its inverse (reverse-complement) k-mer. It holds for many species, both eukaryotes and prokaryotes, for ranges of k which may vary from 7 to 10 as chromosomal lengths vary from 2Mbp to 200 Mbp. Building on this formalism we introduce the concept of k-mer distances between chromosomes. We formulate two k-mer distance measures, D1 and D2, which depend on k. D1 takes into account all k-mers (for a single k) appearing on single strands of the two compared chromosomes, whereas D2 takes into account both strands of each chromosome. Both measures reflect dissimilarities in global chromosomal structures. RESULTS: After defining the various distance measures and summarizing their properties, we also define proximities that rely on the existence of synteny blocks between chromosomes of different bacterial strains. Comparing pairs of strains of bacteria, we find negative correlations between synteny proximities and k-mer distances, thus establishing the meaning of the latter as measures of evolutionary distances among bacterial strains. The synteny measures we use are appropriate for closely related bacterial strains, where considerable sections of chromosomes demonstrate high direct or reversed equality. These measures are not appropriate for comparing different bacteria or eukaryotes. K-mer structural distances can be defined for all species. Because of the arbitrariness of strand choices, we employ only the D2 measure when comparing chromosomes of different species. The results for comparisons of various eukaryotes display interesting behavior which is partially consistent with conventional understanding of evolutionary genomics. In particular, we define ratios of minimal k-mer distances (KDR) between unmasked and masked chromosomes of two species, which correlate with both short and long evolutionary scales. CONCLUSIONS: k-mer distances reflect dissimilarities among global chromosomal structures. They carry information which aggregates all mutations. As such they can complement traditional evolution studies , which mainly concentrate on coding regions.


Assuntos
Cromossomos , Genômica , Inversão Cromossômica , Cromossomos/genética , Eucariotos , Evolução Molecular , Humanos , Sintenia
20.
Zool Res ; 42(5): 671-674, 2021 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-34490760

RESUMO

All extant species in the rodent family Spalacidae are subterranean and have evolved various traits for underground life. However, the phylogenomic relationships among its three subfamilies (Myospalacinae, Spalacinae, and Rhizomyinae) and the molecular basis underlying their adaptations to underground life remain poorly understood. Here, we inferred the phylogenomic relationships among these subfamilies based on de novo sequencing the genome of the hoary bamboo rat ( Rhizomys pruinosus). Analyses showed that ~50% of the identified 11 028 one-to-one orthologous protein-coding genes and the concatenated sequences of these orthologous genes strongly supported a sister relationship between Myospalacinae and Rhizomyinae. The three subfamilies diversified from each other within ~2 million years. Compared with the non-subterranean controls with similar divergence dates, the spalacids shared more convergent genes with the African subterranean mole-rats at the genomic scale due to more rapid protein sequence evolution. Furthermore, these convergent genes were enriched in the functional categories of carboxylic acid transport, vascular morphogenesis, and response to oxidative stress, which are closely associated with adaptations to the hypoxic-hypercapnic underground environment. Our study presents a well-supported phylogenomic relationship among the three subfamilies of Spalacidae and offers new insights into the molecular adaptations of spalacids living underground.


Assuntos
Adaptação Fisiológica/genética , Comportamento Animal/fisiologia , Evolução Molecular , Genômica , Roedores/genética , Animais , Genoma , Filogenia , Roedores/fisiologia , Especificidade da Espécie
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