Habilidad combinatoria de los caracteres relacionados con la producción de habichuela (Phaseolus vulgaris L.)

Las variedades de habichuela cultivadas en Colombia presentan un bajo potencial de producción, por lo que se hace necesario adelantar programas de mejoramiento, cuya ejecución depende del conocimiento de la habilidad combinatoria de los cultivares disponibles. Con el objetivo de evaluar la acción génica predominante en caracteres de importancia económica, se evaluaron 15 híbridos directos y seis progenitores. Las habilidades combinatorias general (HCG) y específica (HCE), se estimaron con el Método 2 modelo 1 de Griffing, que considera a los progenitores y sus cruzamientos directos. Se midieron los caracteres: número de vainas y producción por planta, peso promedio y longitud de la vaina. Los resultados indicaron efectos genéticos aditivos para longitud de la vaina; por el contrario, el número de vainas y producción por planta, se vieron influenciados por efectos genéticos no aditivos, mientras que el peso promedio de la vaina fue controlado por efectos genéticos, tanto aditivos como no aditivos. Los progenitores 1 y 6 mostraron efectos positivos más altos de HCG, para el peso promedio y longitud de la vaina, mientras los progenitores 5 y 6, lo fueron para la producción de vainas por planta y los progenitores 4 y 5, para el número de vainas por planta. La estimación de HCE más alta para todos los caracteres, se presentó en el hibrido 1x2, siendo la más adecuada para mejorar la producción de la habichuela.

Green bean varieties grown in Colombia have low production potential, therefore it is necessary to carry out plant breeding programs, which execution depends on the knowledge of the combinatorial ability of the available cultivars. To evaluate the predominant gene action in economically important traits 15 direct hybrids and six parents were evaluated. General combining ability (GCA) and specific combining ability (SCA) were estimated with Griffing's Method 2 model 1, which considers parents and their direct crosses. The characters: number of pods and yield per plant, average weight and pod length were measured. The results indicated additive genetic effects for pod length. In contrast, pod number and yield per plant were influenced by non-additive genetic effects, while average pod weight was controlled by both additive and non-additive genetic effects. Parents 1 and 6 showed higher positive effects of HCG for average pod weight and pod length, while parents 5 and 6 for pod yield per plant and parents 4 and 5 for number of pods per plant. The highest ECGH estimation for all traits was found in the 1x2 hybrid, being the most suitable for improving bean production.

Investigation of associations between apolipoprotein A5 and C3 gene polymorphisms with plasma triglyceride and lipid levels

SUMMARY OBJECTIVE: The aim of this study was to determine frequency and associations between APOA5 c.56C>G, −1131T>C, c.553G>T, and APOC3 −482C>T and SstI gene polymorphisms with hypertriglyceridemia. METHODS: Under a case-control study model, 135 hypertriglyceridemic and 178 normotriglyceridemic control participants were recruited. Polymerase chain reaction and restriction fragment length polymorphism methods were utilized for genotyping. Statistical calculations were performed by comparing allele and genotype frequencies between groups. Clinical characteristics were compared between groups and intra-group genotypes. RESULTS: APOC3 gene −482C>T and SstI polymorphic genotypes and allele frequencies were significantly higher in hypertriglyceridemic group (genotype frequencies, p=0.035, p=0.028, respectively). Regression analysis under unadjusted model confirmed that APOC3 −482C>T and SstI polymorphisms were significantly contributing to have hypertriglyceridemia (p=0.02, odds ratio [OR]=1.831 (95% confidence interval [CI] 1.095-3.060); p=0.04, OR=1.812 (1.031-3.183), respectively). APOA5 c.56C>G was in complete linkage disequilibrium with APOA5 c.553G>T polymorphism (D'=1). CONCLUSION: For the first time in a population sample from Turkey, among the five polymorphisms of APOA5 and APOC3 genes investigated, APOC3 −482C>T and SstI polymorphisms were associated with elevated serum TG levels, while APOA5 c.56C>G, −1131T>C, and c.553G>T polymorphisms were not.

Impact of pharmacogenetics on aspirin resistance: a systematic review / Impacto da farmacogenética na resistência à aspirina: uma revisão sistemática

Abstract Background Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR). Objectives To realize a systematic literature review to determine the impact of genetic variants on AR. Methods Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included. Results The genetic variants rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2), and rs5918 (ITGB3) were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance (p< 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 and rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 and rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP), and rs662 (PON1), while these differ in real interference in AR: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1), and rs20417 (PTGS2). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences. Conclusion It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR.

Resumo Antecedentes A farmacogenética promete melhorar o controle de doenças como as cardiovasculares. O ácido acetilsalicílico, a aspirina, previne a formação de um agente ativador da agregação plaquetária e vasoconstrição e é usado na prevenção de tais doenças. No entanto, os pacientes podem ter falha no tratamento devido a variantes genéticas que modificam o metabolismo da droga causando resistência à aspirina (RA). Objetivos Realizar uma revisão sistemática da literatura para determinar o impacto das variantes genéticas na resistência à aspirina. Métodos Artigos publicados nos bancos de dados MEDLINE/PubMed, Cochrane, Scopus, LILACS e SCIELO foram sistematicamente selecionados. Foram identificados 290 artigos e, destes, 269 artigos foram excluídos por não atenderem aos critérios de inclusão previamente estabelecidos. Um total de 20 estudos caso-controles e 1 coorte foi incluído. Resultados As variantes genéticas rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2) e rs5918 (ITGB3) foram as mais estudadas. Quanto à relevância, das 64 variantes genéticas avaliadas pelos artigos, 14 tiveram significância estatística (p< 0,05; intervalo de confiança [IC] de 95%) em pelo menos um artigo. Entre eles, os seguintes tiveram resultados unânimes: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 e rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 e rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP) e rs662 (PON1), enquanto estes diferiram na interferência real na RA: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1) e rs20417 (PTGS2). Como limitações do estudo, destacam-se as metodologias não uniformes dos artigos analisados e as diferenças populacionais. Conclusão Vale ressaltar que a farmacogenética é uma área em expansão. Portanto, mais estudos são necessários para entender melhor a associação entre variantes genéticas e RA.

Clinical features and genetic variations of Axenfeld-Rieger syndrome / 中华实验眼科杂志

Axenfeld-Rieger syndrome is a rare autosomal dominant hereditary disease characterized by anterior segment dysgenesis, which may be accompanied by various systemic defects, including craniofacial dysmorphism, hypodontia, microdontia, and redundant periumbilical skin.Its typical ocular manifestations include posterior embryotoxon, iris hypoplasia, peripheral anterior synechiae, corectopia and polycoria with a high prevalence of glaucoma.Patients can exhibit any combination of these features.However, family members with the same genotype may present different phenotypes due to phenotypic heterogeneity.Emerging evidence suggests that PITX2 and FOXC1 genes encoding transcription factors are primarily associated with genetic variants in ARS.Intragenic mutations and gene deletions are common types of genetic variations suspected to trigger changes in gene dosages and protein function.However, the underlying molecular mechanism remains unclear.Some patients with ARS carry mutations in the COL4A1, PRDM5, and CYP1B1 genes, but the pathogenicity of these variations has yet to be confirmed by further studies.This article provided an overview of the typical clinical features, potential correlations between phenotype and genotype, as well as gene function.

Interpretation of standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology / 中华实验眼科杂志

Sequencing technology has evolved rapidly with the advent of high-throughput next-generation sequencing (NGS). By adopting NGS, more and more ophthalmologists and medical institutions are now performing genetic testing for molecular diagnosis and genetic research in genetic ocular disorders.Genetic testing has gradually become an indispensable test item in the diagnosis and treatment of patients with monogenetic ocular diseases and has been accompanied by new challenges in sequence interpretation due to increased complexity.As we know, NGS can detect a large number of the genetic variation data.Without strict standards to distinguish pathogenic variation from many potential functional variations in the human genome, false positive judgments of causality may be accelerated, which may hind the application and promotion of genetic diagnosis in clinical diagnosis as well as the biological understanding of diseases.The American College of Medical Genetics and Genomics (ACMG) has developed guidances for the interpretation of sequence variants and the Chinese Branch of Genetic Counseling has organized some experts in the field of genetic compiled the Chinese version of the ACMG Standards and Guidelines, which is one of the reference bases to help us interpret genetic variation.This article interpreted the ACMG Standards and Guidelines in order to provide reference for Chinese ophthalmologists in the classification of genetic variation, determination of pathogenic variation, application in clinical diagnosis and related genetic research.

VPS13B gene variation and clinical phenotype of Cohen syndrome in a Chinese Han family / 中华实验眼科杂志

Objective:To analyze the pathogenicity and clinical characteristics of patients with Cohen syndrome caused by a compound heterozygous variation of VPS13B gene. Methods:A pedigree investigation was conducted.A Chinese Han family with Cohen syndrome was recruited from Henan Eye Hospital in September 2021.There were three members of two generations in this family, including one patient.The clinical data of the proband and his parents were collected, and the relevant ophthalmic and general examinations were performed to evaluate the clinical phenotype.The peripheral venous blood samples of the family members were collected to extract whole genomic DNA, and the whole exome sequencing was performed.Sanger sequencing and pedigree co-segregation analysis were performed among the family members.According to the ACMG guidelines, the pathogenicity of the selected variants was evaluated and the online tools were used to predict the pathogenicity of the variants.Relevant literature of Cohen syndrome were retrieved in Online Mendelian Inheritance in Man (OMIM) and PubMed, China National Knowledge Infrastructure and Wanfang databases by taking Cohen syndrome and VPS13B gene as the searching keywords.The clinical manifestations and pathogenic variants of patients in the literature were summarized, and the relationship between genotype and clinical phenotype was analyzed.This study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). Both the subject and the patient's guardian were aware of the study purpose and method.Written informed consent was obtained. Results:The family was consistent with autosomal recessive inheritance.The proband, a 5-year-old male, had bilateral night blindness with photophobia, ptosis, lower eyelid entropion, and trichiasis; high myopia in both eyes; osteoblastoid pigmentation in the peripheral retina, atrophy and thinning of the outer layer of the peripheral retina, extinguished flashing electroretinogram; global growth retardation, typical facial features, slender fingers and toes, flatfoot, foot valgus, dystonia, no cardiac abnormalities; excessively cheerful personality.The clinical manifestations of the proband were consistent with Cohen syndrome.No obvious abnormality was found in the clinical phenotype and the auxiliary examination of the proband's parents.Whole exon sequencing revealed that the proband carried two heterozygous variations, a nonsense variation c. 11713C>T(p.Gln3905*) and a splicing variation c. 6940+ 1G>T.Sanger sequencing confirmed that the above variations were co-segregated in this family.c.11713C>T(p.Gln3905*) was a novel variant, which prematurely terminated the protein encoded by it and affected the normal function of the protein.The two variations were pathogenic variants according to the ACMG guidelines.A total of 12 articles on variants and clinical characteristics of Cohen syndrome in China were retrieved.Combined with the results of this study, a total of 24 VPS13B variants were found in Chinese patients, of which the incidence of frameshift variation was 41.7%(10/24), missense variation 20.8%(5/24), splicing variation 20.8%(5/24) and nonsense variation 16.7%(4/24), respectively.The onset age of patients with Cohen syndrome was from 28 days to 12 years old.The symptoms such as nerve system, eye, brain, and bone were sporadic, and the clinical manifestations were highly heterogeneous. Conclusions:A novel pathogenic variation c. 11713C>T is found in the VPS13B gene of the Cohen syndrome pedigree in this study, and expands the pathogenic variation spectrum of the VPS13B gene.The clinical manifestations of Cohen syndrome are highly heterogeneous.

Research Progress of Key Molecular Events Related to Progression of Colorectal Cancer / 肿瘤防治研究

The continuous development of high-throughput and single-cell sequencing technologies and the emergence of spatial transcriptome sequencing have allowed the continuous discovery of temporal and spatial molecular events in the progression of colorectal cancer (CRC) to better understand its mechanism of malignant progression. Genetic variations (mutation of APC and P53, etc.) and mismatch repair of DNA, posttranscriptional regulation, such as epigenetic alteration, and dynamic alteration of complex molecular networks have their own special molecules that play key roles. Drug resistance and metastasis in the late stage of CRC progression are closely related to these key molecular events. This article reviews the research progress and explores key molecular events in the malignant progression of CRC to provide scientific basis and ideas for elucidating the regulatory mechanism of CRC and evaluating its prognosis prediction and treatment.

Ancestry and self-reported race in Brazilian breast cancer women

SUMMARY OBJECTIVE: This study aimed to evaluate the association between self-reported race/color and ancestry in Brazilian patients with breast cancer. METHODS: This was an observational, transversal, epidemiological study, evaluating race and ancestry in 1,127 patients with breast cancer. For genetic ancestry, a 46-AIM-INDEL panel was used. The ancestral profile was evaluated with the Structure v.2.3.3 software. Descriptive statistics were performed. To assess differences between race and ancestry, an analysis of variance with Bonferoni adjustment was used. RESULTS: The race distribution was 77.7% white, 17.6% brown, 4.1% black, 0.4% yellow, and 0.3% cafuse. The African ancestry proportion was significantly (p<0.001) more evident in black [0.63±0.21 (0.17-0.96)], followed by brown [0.25±0.16 (0.02-0.70)], and less frequent in white skin color. The European ancestry proportion was significantly (p<0.001) higher in white [0.72±0.17 (0.02-0.97)], followed by brown [0.57±0.19 (0.12-0.92)], yellow [0.27±0.31 (0.12-0.620], and black [0.24±0.19 (0.02-0.72)]. The Asiatic ancestry proportion is significantly (p<0.001) higher in yellow [0.48±0.51 (0.04-0.93)]. The Amerindian ancestry proportion frequency was the least frequent in all groups, and cafuse patients did not express differences between all race groups. The brown race group presented differences in African and European ancestry. CONCLUSION: Although we found many similarities between white European ancestry, black African ancestry, and yellow Asian ancestry, there is great miscegenation between patients. Although they can be labeled as having one race, they do present many ancestral genes that would allow their inclusion in another race group.

Genetic testing for cannabinoid use / Testes genéticos para uso de canabinoides

ABSTRACT BACKGROUND AND OBJECTIVES: Cannabis is the most popular and consumed illicit drug in the world, it has about 540 bioactive phytocannabinoids, including tetrahydrocarbinol (THC) and cannabidiol (CBD). The therapeutic potential of phytocannabinoids has been the subject of many studies in recent decades for many medical situations, including the management of chronic pain. The advent of pharmacogenetics currently allows the indication of the Cannabis dose to be evaluated individually. The objective of this work was to carry out a survey of the literature on the medicinal use of Cannabis and the application of pharmacogenetics in this therapy. CONTENTS: THC and CBD phytocannabinoids are the most abundant and researched. In the endocannabinoid system there are compounds similar to phytocannabinoids, cell receptors and metabolism enzymes. All these molecules are secreted from genes, which may have individual genetic polymorphisms that determine the modulation of the endocannabinoid system, and consequently impact the patients' therapeutic response. CONCLUSION: The existence of genetic tests for the prior assessment of the patients genetic profile in order to avoid side effects and to have more assertiveness in the indication of the cannabis product is an important tool to increase adherence to cannabis treatment.

RESUMO JUSTIFICATIVA E OBJETIVOS: A cannabis é a droga ilícita mais popular e consumida no mundo, possuindo cerca de 540 fitocanabinoides bioativos, entre eles o tetra-hidrocarbinol (THC) e o canabidiol (CBD). O potencial terapêutico dos fitocanabinoides tem sido alvo de muitos estudos nas últimas décadas para muitas situações médicas, incluindo o manejo da dor crônica. O advento da farmacogenética permite que atualmente a indicação da dose de cannabis seja avaliada individualmente. O objetivo deste estudo foi realizar um levantamento da literatura sobre o uso medicinal da cannabis e a aplicação da farmacogenética nessa terapia. CONTEÚDO: Os fitocanabinoides THC e CBD são os mais abundantes e pesquisados. No sistema endocanabinoide, existem compostos similares aos fitocanabinoides, receptores celulares e enzimas de metabolismo. Todas essas moléculas são secretadas a partir de genes que podem possuir polimorfismos genéticos individuais determinantes para a modulação do sistema endocanabinoide e, consequentemente, impactam a resposta terapêutica do paciente. CONCLUSÃO: A existência de testes genéticos para avaliação prévia do perfil genético do paciente a fim de evitar efeitos colaterais e ter mais assertividade na indicação do produto de cannabis é uma importante ferramenta para aumentar a aderência ao tratamento com cannabis.

The challenge of finding Chinese blood groups / 中国输血杂志

Up to now, hundreds of human blood groups have been detected globally, but none have been found in the Chinese population. China is a multi-ethnic country with rich genetic polymorphism and variation. The Chinese pangenome reference reveals that the Chinese carry some genetic variations that are different from other ethnic groups in the world, especially the discovery of approximately 5 million new base pair sequences, which are considered the core genome sequences of the Chinese population. Research on red blood cell membrane proteomics has shown that red blood cells carry over 2 600 kinds of erythrocyte membrane proteins, and currently only 37 protein molecules have detected blood group antigens. The above data suggest that the possibility of new blood group in the Chinese population cannot be ruled out. This comment describes the history of the discovery of blood groups and the challenges faced by Chinese scholars.

Prenatal diagnosis of fetal diencephalic-mesencephalic junction dysplasia: a case report / 中华围产医学杂志

We report a case of fetal diencephalic-mesencephalic junction dysplasia (DMJD) diagnosed prenatally. Prenatal ultrasound at 24 gestational weeks showed that the fetus was small, about the size at 22 weeks' gestation, with short biparietal diameter and enhanced echo at the anterior border of thalamus. Fetal MRI showed short T2 signal shadow in the left choroid plexus, and hemorrhage and midbrain dysplasia were suspected. A pathogenic homozygous mutation variant in protocadherins 12 gene (c.1558C>T) was found in this fetus by whole exome sequencing and both parents carried the same heterozygous variation revealed by Sanger sequencing. All of the above information lead to the diagnosis of fetal DMJD, and the pregnancy was terminated after genetic counseling.

A case of mental retardation autosomal dominant 35 with neonatal onset / 中华围产医学杂志

This article reported a male patient with neonatal onset mental retardation autosomal dominant 35 (MRD35). The boy presented with repeated convulsions, hypotonia, enlarged head circumference, congenital muscular torticollis and feeding difficulties in the neonatal period. Dynamic electroencephalogram showed paroxysmal epileptic discharges in the left central-temporal region. High-throughput whole-exome sequencing revealed a heterozygous mutation of c.139G>A (p.Glu47Lys) in the PPP2R5D gene, which was a de novo mutation not inherited from his parents. The child had significant developmental delay at the age of one year. MRD35 lacks typical clinical manifestations and requires whole-exome sequencing for definitive diagnosis. Currently, there is no specific treatment for MRD35 and symptomatic treatments, including rehabilitation training, language training and seizure control, are mostly adopted.

Inherited protein C deficiency in pregnancy: a case report / 中华围产医学杂志

This paper reported the management of a pregnant women with inherited protein C deficiency. The patient had a history of recurrent deep vein thrombosis before pregnancy and was diagnosed with inherited protein C deficiency by a pedigree-based whole exome sequencing, which revealed PROC gene mutations. She received anticoagulation treatment and was managed by a multidisciplinary team during pregnancy. No significant abnormalities were found during routine prenatal examination and a male infant was delivered vaginally at 38 +2 gestational weeks. No postpartum hemorrhage was reported and the maternal and infant outcomes were good. The management of such patients during pregnancy mainly relied on anticoagulation therapy to avoid serious thrombotic events and ensure the safety of the mothers and fetuses.

Donohue syndrome caused by mutation of insulin receptor gene: a case report / 中华围产医学杂志

This article reported the comprehensive management and short-term follow-up of a neonate diagnosed with Donohue syndrome. The affected male neonate presented with obvious insulin resistance (uncontrollable hyperglycemia) and unusual facies (more hair and dense, wide eye distance, large ears, etc.). Whole exome sequencing revealed a compound heterozygous variant in the insulin receptor gene [c.3258+4A>G in intron 17 and c.1321T>A (p.W441R) in exon 6], and Sanger sequencing confirmed that the mutation was inherited from both parents, which is likely pathogenic mutation. Based on the genetic test results and clinical manifestation, the neonate had a high probability of being diagnosed with Donohue syndrome. During a follow-up of nine months, the baby showed growth and development retardation, intermittent low-grade fever, and the fasting glucose was around 18 mmol/L.

A neonate with filamin A gene-associated periventricular nodular heterotopia / 中华围产医学杂志

This paper reported a neonate with periventricular nodular heterotopia associated to filamin A ( FLNA) gene mutation. The female patient was born at 29 +6 weeks of gestation to a mother who had intractable seizures and a history of two adverse pregnancy outcomes. Postnatal cranial ultrasound showed multiple hypoechoic masses on the walls of bilateral ventricles, which presented as "sawtooth pattern". MRI revealed gray matter displacement, unclear edge of gray and white matter, wavy bilateral ventricles and multiple nodular signals. Whole exon sequencing showed that the patient carried a maternally-inherited and likely pathogenic heterozygous mutation of chrX:153579307 in the FLNA gene (NM_00111 0556; p.Glu2376fsTer9), which caused the periventricular nodular heterotopia in the neonate. The patient was followed up until eight months of age and no convulsion or obvious abnormality in her growth or development was reported.

Nonsense variation of OTUD5 gene in a fetus with X-linked multiple congenital anomalies- neurodevelopmental syndrome / 中华围产医学杂志

We report a fetus presented with complex cardiac malformations, pulmonary atresia with ventricular septal defect, detected by fetal echocardiography at 17 +4 weeks. The pregnancy was terminated after routine counseling and genetic tests were performed on umbilical cord of the induced fetus and peripheral blood samples of the parents. Whole-exome sequencing identified a novel maternally-inherited and likely pathogenic variation hemizygous nonsense variant, c.1651C>T (p.Gln551*) in the OTUD5 gene (NM_017602.3), which was confirmed by subsequent Sanger sequencing. The fetus was finally diagnosed as X-linked multiple congenital anomalies-neurodevelopmental syndrome.

A family of Niemann-Pick disease type C caused by compound heterozygous mutations in NPC1 gene / 中华神经科杂志

Objective:To report the clinical and genetic characteristics of a family with Niemann-Pick disease type C caused by novel compound heterozygous mutations in the NPC1 gene to improve the clinicians′ recognition of the disease. Methods:Two patients from the family with non-consanguineous marriages admitted to the Department of Neurology of the First Affiliated Hospital of Kunming Medical University in 2020 were examined in detail. Peripheral blood DNA was extracted, and whole exome sequencing was performed on the patients, combined with Sanger sequencing for verification. The mutation and protein function predictor softwares were applied to analyze the mutation sites.Results:The inheritance was autosomal recessive in this family. The onset age of the proband was 9 years, and the main clinical manifestations were dysarthria, dysphagia, cognitive impairment, ataxia, bilateral pyramidal tract impairment, vertical supranuclear gaze palsy and splenomegaly. The clinical phenotype of the proband′s younger brother was similar to that of the proband, but it was more severe than that of the proband. The younger brother of the proband had an earlier age of onset and severe psychomotor retardation. Whole exome sequencing showed that both brothers carried 2 rare variants of NPC1 gene:1 pathogenic, stop gain at c.352_353del, p.Gln119ValfsTer8, and a missense change, c.593A>G, p.Asn198Ser, of suspected pathogenic. Sanger sequencing confirmed that compound heterozygous mutations were derived from the proband′s parents. According to the American College of Medical Genetics and Genomics guidelines, the above variants were rated as pathogenic and suspected pathogenic, respectively. And the c.593A>G, p.Asn198Ser mutation found in this family was a novel one which had not been reported yet. The proband had delayed diagnosis for 7 years from the onset of symptoms. After taking megastat for 1 year, the symptoms of dysphagia, ataxia and vertical eye movement disorder were significantly improved. Conclusions:The clinical phenotype of the pedigree was consistent with the clinical phenotype of Niemann-Pick disease type C. Compound heterozygous mutations of NPC1 gene (c.352_353del; c.593A>G) were found to be the genetic cause of the family.

Association between smoking and ankylosing spondylitis: a Mendelian randomization study / 预防医学

Objective@#To evaluate the association of smoking with the risk of ankylosing spondylitis (AS) using a Mendelian randomization (MR) approach.@*Methods@#A total of 16 383 186 AS-associated single nucleotide polymorphisms (SNPs), 378 smoking initiation associated SNPs and 126 lifetime smoking score-associated SNPs were collected from three large-scale genome-wide association studies (GWAS). The association of smoking phenotypes with the risk of AS was examined using inverse-variance weighted (IVW) with AS as a outcome variable, smoking initiation and lifetime smoking score as exposure factors and SNPs with strong associations with smoking as instrumental variables, and sensitivity analyses were performed with maximum likelihood-based method, MR pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression analysis.@*Results@# A 33.5% increased risk of AS was found among genetically predicted smokers relative to non-smokers (OR=1.335, 95%CI: 1.059-1.682), and an increase in predicted lifetime smoking by per standard deviation resulted in a 101.4% increased risk of AS (OR=2.014, 95%CI: 1.341-3.024). The maximum likelihood-based method and MR-PRESSO test showed consistent correlated effect estimations and MR-Egger regression analysis identified no evidence of pleiotropy.@*Conclusion@#It is genetically predicted that smoking is associated with an increased risk of AS.

Caracterização genética, clínica e epidemiológica de pacientes com Covid-19 em uma região do Sul do Brasil / Genetic, clinical and epidemiological characterization of Covid-19 patients in South Brazil

Caracterizar o perfil epidemiológico, clínico e genético de pacientes com Covid-19. Realizou-se um estudo observacional e transversal com voluntários que tiveram diagnóstico de Covid-19 no período de abril de 2020 a maio de 2021 no município de Santa Cruz do Sul (RS, Brasil), no qual foram coletados dados clínicos e epidemiológicos, além de amostras de sangue para a identificação de polimorfismos no gene ACE2. Foram recrutados 87 indivíduos e destes, 16,7% necessitaram de internação hospitalar, sendo a maioria do sexo masculino. A obesidade foi a comorbidade mais frequente, no entanto, doenças cardiovasculares, hipertensão e diabetes apresentaram maior significância quando associadas às internações. Em relação à características genéticas, entre os voluntários não foram encontrados polimorfismos no gene ACE2. A pesquisa sugere que o sexo masculino e presença de comorbidades são importantes fatores de risco para a severidade da Covid-19.

Current paper characterizes the epidemiological, clinical and genetic profile of patients with Covid-19. An observational and cross-sectional study was carried out with volunteers diagnosed with Covid-19 between April 2021 and May 2021 in the municipality of Santa Cruz do Sul, Brazil; a blood sample also identified polymorphism in the ACE2 gene. 87 patients were recruited; 6.7% required hospitalization, the majority being male. Although obesity was a more frequent co-morbidity, cardiovascular diseases, hypertension and diabetes were more significant when associated with hospitalizations. In the case of genetic characteristics, polymorphisms were found in the ACE2 gene among volunteers. Important research suggests male gender and co-morbidities are risk factors for the severity of Covid-19.

Variation characteristics of gag gene of human immunodeficiency virus type 1 strain in the main epidemic areas of acquired immunodeficiency syndrome in Yunnan Province / 中华传染病杂志

Objective:To analyze the variation characteristics of gag gene sequence of human immunodeficiency virus type 1 (HIV-1) epidemic strains in four major acquired immunodeficiency syndrome (AIDS) endemic areas in Yunnan Province. Methods:A total of 480 human immunodeficiency virus (HIV)/AIDS patients from designated antiviral treatment institutions in Kunming City, Dehong Dai and Jingpo Autonomous Prefecture, Hani-Yi Autonomous Prefecture of Honghe and Lincang City in Yunnan Province from January 2019 to December 2020 were randomly selected. The epidemiological information of the patients was collected. The plasma samples were collected and sent to the Yunnan Provincial Infectious Diseases Hospital for analysis. HIV-1 gag gene was amplified by nested polymerase chain reaction for genotyping.The phylogenetic tree was constructed by MEGA 6.06, and the characteristic amino acids were analyzed by VESPA online analysis tool. The gene distances of gag and matrix protein p17, capsid protein p24, nucleocapsid protein p7 and p6 protein of gag protein were calculated by Distance program. The ratio of synonymous mutation frequnency and non-synonymous mutation frequnency (Ks/Ka) was analyzed by SNAP program. Statistical comparison among multiple groups was performed using analysis of variance. Results:The gag gene sequences were successfully obtained from 404 patients.Most of these patients were men (250 cases, 61.9%), 59.7%(241/404) of patients were aged 40 to 59 years, and the main transmission route was heterosexual transmission (61.4%, 248/404). The main epidemic subtypes of HIV-1 were circulating recombinant form(CRF)08_BC (38.4%, 155/404), CRF01_AE (18.3%, 74/404), unique recombinant form (URF) (12.9%, 52/404), CRF07_BC(9.7%, 39/404), C subtype (8.4%, 34/404), other subtypes (6.9%, 28/404) and B subtype (5.4%, 22/404). Two main spreading clusters were formed by CRF08_BC in the phylogenetic tree, and there were significant differences in the distribution of characteristic amino acids of eight loci between the two spreading clusters, including No.79, 93, 121, 122, 151, 363, 395 and 396. The gag gene distances of CRF01_ AE, CRF07_ BC and CRF08_ BC were 0.090±0.004, 0.088±0.004 and 0.078±0.002, respectively, and the difference was statistically significant ( F=118.33, P<0.001). The Ks/Ka values of gag of the three subtypes were 4.003±1.309, 4.141±0.860 and 4.514±1.215, respectively, and the difference was statistically significant ( F=1.35, P<0.001). The Ks/Ka values of p17 were 2.590±0.186, 2.831±0.496 and 2.936±0.475, respectively, and the difference was statistically significant ( F=1.59, P<0.001). The Ks/Ka values of p24 were 12.579±1.116, 10.185±0.494 and 8.522±0.595, respectively, and the difference was statistically significant ( F=1.61, P<0.001). The Ks/Ka values of p7 were 10.850±0.711, 9.717±0.932 and 8.522±0.026, respectively, and the difference was statistically significant ( F=4.24, P<0.001). The Ks/Ka values of p6 were 3.122±0.134, 3.040±1.498 and 4.841±0.353, respectively, and the difference was statistically significant ( F=10.68, P<0.001). Conclusions:CRF08_ BC is the main subtype in these four areas in Yunnan Province.The different clusters of CRF08_BC result in a different pattern of amino acid composition.The variation degree of different subtype gag gene is different in each section. Surveillance of HIV variant strains should be strengthened to control the epidemics of HIV.