Research Development in Patients with Olmsted Syndrome / 罕见病研究

Olmsted syndrome (OS) is an extremely rare hereditary skin disease, that is usually characterized by mutilating palmoplantar keratoderma (PPK) and periorificial keratotic plaques. The diagnosis of this disease depends primarily on the clinical presentation and OS has to be differentiated from other disorders associated with hyperkeratosis. In recent years, there have been many advances in molecular genetic research on the pathogenesis of the disease. The genes that can cause disease after specific mutations include TRPV3, MBTPS2/S2P and PERP. Therefore, genetic testing has become one of the important methods for the diagnosis of this disease.OS treatment is difficult, and conventional therapy uses topical drugs to soften the cuticle of the skin, or oral Avi A.Excision of palmoplantar keratosis may also be used for constricting rings that severely restrict movement, but they often reoccur after initial improvement. In terms of precision treatment, researchers have tried the small molecule drugs erlotinib and sirolimus and have achieved some results. This paper summarizes the etiology, pathogenesis, clinical manifestations, diagnosis, treatment and prognosis of OS, in order to improve the clinicans' awareness of OS.

Research on genetic model of keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of genetic factors on the pathogenesis of keratoconus and its genetic model.METHODS: Genetic epidemiological methods were used to investigate the prevalence of keratoconus in 280 first-degree relatives of 100 patients with keratoconus who attended Henan Eye Hospital between July 2020 and April 2023. The heritability was estimated by Falconer regression method. The general genetic model was calculated using Penrose method, and the genetic model was confirmed by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory.RESULTS: The results showed that there were 16(5.714%)first-degree relatives of keratoconus probands suffering from keratoconus, and the heritability of keratoconus was(86.100±7.400)%. The S/q score calculated by the Penrose method was 35.348, which was near to 1/(q)1/2, suggesting that the genetic model of keratoconus might be polygenic inheritance. The expected prevalence in first-degree relatives of keratoconus patients by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory were 5.900%, 7.714% and 5.700%, respectively, which showed no significant differences from the actual prevalence(5.714%), suggesting that keratoconus was a polygenetic disease.CONCLUSION:Genetic factors might play an important role in the pathogenesis of keratoconus, and keratoconus is a polygenetic disease.

Two-phase SSU and SKAT in genetic association studies

The sum of squared score (SSU) and sequence kernel association test (SKAT) are the two good alternative tests for genetic association studies in case–control data. Both SSU and SKAT are derived through assuming a dose-response model between the risk of disease and genotypes. However, in practice, the real genetic mode of inheritance is impossible to know. Thus, these two tests might lose power substantially as shown in simulation results when the genetic model is misspecified. Here, to make both the tests suitable in broad situations, we propose two-phase SSU (tpSSU) and two-phase SKAT (tpSKAT), where the Hardy–Weinberg equilibrium test is adopted to choose the genetic model in the first phase and the SSU and SKAT are constructed corresponding to the selected genetic model in the second phase. We found that both tpSSU and tpSKAT outperformed the original SSU and SKAT in most of our simulation scenarios. By applying tpSSU and tpSKAT to the study of type 2 diabetes data, we successfully identified some genes that have direct effects on obesity. Besides, we also detected the significant chromosomal region 10q21.22 in GAW16 rheumatoid arthritis dataset, with P \10-6 . These findings suggest that tpSSU and tpSKAT can be effective in identifying genetic variants for complex diseases in case–control association studies

Choice of genetic model on Meta-analysis of genetic association studies: introduction of genetic model-free approach for Bayesian analysis / 中华流行病学杂志

Meta-analysis used for genetic association studies became popular among researchers,with the amount of published papers increased rapidly.In this paper,we will focus on the introduction on the selection of genetic models.Traditionally,methods used for Meta-analysis on genetic association studies was to calculate the statistics based on available genetic models which not only increasing the probability of false-positives but also making the interpretation of results more difficult.Hence,a critical step in the Meta-analysis of genetic association studies was to choose the appropriate inheritance model.The aim of this paper was to introduce the theory of Bayesian analysis regarding the genetic model-free approach,in performing the Meta-analysis for studies related to genetic associations.

Choice of genetic model on Meta-analysis of genetic association studies: introduction of genetic model-free approach for Bayesian analysis / 中华流行病学杂志

Meta-analysis used for genetic association studies became popular among researchers,with the amount of published papers increased rapidly.In this paper,we will focus on the introduction on the selection of genetic models.Traditionally,methods used for Meta-analysis on genetic association studies was to calculate the statistics based on available genetic models which not only increasing the probability of false-positives but also making the interpretation of results more difficult.Hence,a critical step in the Meta-analysis of genetic association studies was to choose the appropriate inheritance model.The aim of this paper was to introduce the theory of Bayesian analysis regarding the genetic model-free approach,in performing the Meta-analysis for studies related to genetic associations.

Genetic analysis for anthocyanin and chlorophyll contents in rapeseed / Análise genética para antocianinas e de clorofila em sementes de colza

ABSTRACT: Rapeseed (Brassica napus L.) with purple-red leaf is a valuable resource for plant breeder. It was utilized in breeding program as a morphological marker, and the source of resistance gene to biotic or abiotic stress due to its anthocyanin content (AC). However, the inheritance of AC and the correlation with chlorophyll content (CC) in rapeseed leaf are still unknown. This study aimed to investigate the gene action and heritability of AC and CC in a 10-Zi006 × 10-4438 rapeseed cross using generation mean analysis. The results indicated that AC and CC were controlled by main gene effect and non-allelic interactions. The AC was mainly controlled by genetic effect. However, the genetic effect and non-genetic effect were both important for CC. In addition, the total fixable gene effects was higher than unfixable gene effects for AC, but opposite results was found for CC. Both negative and positive correlations between AC and CC were obtained in different generations.

RESUMO: Colza (Brassica napus L.) de folhas vermelho-púrpura é um recurso valioso para os produtores. Foi utilizada em programas de melhoramento como um marcador morfológico ao gene de resistência a estresses abióticos, bióticos ou devido ao seu teor de antocianinas (AC). No entanto, a herança da AC e a correlação com o teor de clorofila (CC) na folha de colza ainda são desconhecidos. Este estudo teve como objetivo investigar a ação dos genes e hereditariedade da CA e CC em 10 Zi006 × 10-4438 colza, usando geração de análise. Os resultados indicaram que CA e CC foram controladas por efeito do gene principal e interacções não-alélicas. O AC foi controlado principalmente por efeito genético. No entanto, os efeitos genético e não genético foram ambos importantes para CC. Além disso, o total de efeitos gênicos solucionáveis foi maior do que os efeitos de genes para AC, mas os resultados opostos foram encontrados para CC. Correlações negativas e positivas entre CA e CC foram obtidas em diferentes gerações.

Genetic association study of P2x7 A1513C (rs 3751143) polymorphism and susceptibility to pulmonary tuberculosis: A meta-analysis based on the findings of 11 case-control studies

OBJECTIVE@#To summarize the precise association between pulmonary tuberculosis (PTB) and P2x7 A1513C gene polymorphism.@*METHODS@#PubMed and Google Scholar web-databases were searched for the studies reporting the association of P2x7 A1513C polymorphism and PTB risk. A meta-analysis was performed for the selected case-control studies and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all the genetic models.@*RESULTS@#Eleven studies comprising 2678 controls and 2113 PTB cases were included in this meta-analysis. We observed overall no significant risk in all the five genetic models. When stratified population by the ethnicity, Caucasian population failed to show any risk of PTB in all the genetics models. In Asian ethnicity, variant allele (C vs. A: P = 0.001; OR = 1.375, 95% CI = 1.159-1.632) and heterozygous genotype (AC vs. AA: P = 0.001; OR = 1.570, 95% CI = 1.269-1.944) demonstrated significant increased risk of PTB. Likewise, recessive genetic model (CC + AC vs. AA: P = 0.001; OR = 1.540, 95% CI = 1.255-1.890) also demonstrated increased risk of PTB in Asians.@*CONCLUSIONS@#Our meta-analysis did not suggest the association of P2x7 A1513C polymorphism with PTB risk in overall or separately in Caucasian population. However, it plays a significant risk factor for predisposing PTB in Asians. Future larger sample and expression studies are needed to validate this association.

Genetic association study of P2x7 A1513C (rs 3751143) polymorphism and susceptibility to pulmonary tuberculosis: A meta-analysis based on the findings of 11 case–control studies

Objective To summarize the precise association between pulmonary tuberculosis (PTB) and P2x7 A1513C gene polymorphism. Methods PubMed and Google Scholar web-databases were searched for the studies reporting the association of P2x7 A1513C polymorphism and PTB risk. A meta-analysis was performed for the selected case–control studies and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all the genetic models. Results Eleven studies comprising 2 678 controls and 2 113 PTB cases were included in this meta-analysis. We observed overall no significant risk in all the five genetic models. When stratified population by the ethnicity, Caucasian population failed to show any risk of PTB in all the genetics models. In Asian ethnicity, variant allele (C vs. A: P = 0.001; OR = 1.375, 95% CI = 1.159–1.632) and heterozygous genotype (AC vs. AA: P = 0.001; OR = 1.570, 95% CI = 1.269–1.944) demonstrated significant increased risk of PTB. Likewise, recessive genetic model (CC + AC vs. AA: P = 0.001; OR = 1.540, 95% CI = 1.255–1.890) also demonstrated increased risk of PTB in Asians. Conclusions Our meta-analysis did not suggest the association of P2x7 A1513C polymorphism with PTB risk in overall or separately in Caucasian population. However, it plays a significant risk factor for predisposing PTB in Asians. Future larger sample and expression studies are needed to validate this association.

Estimativas de variância genética aditiva em populações selecionadas e não-selecionadas via simulação Monte Carlo utilizando o software R / Additive genetic variance estimates in selected and unselected populations via Monte Carlo simulation using the R software

Para disponibilizar um sistema de fornecimento de dados que objetivando-se subsidiar pesquisas de Melhoramento Genético Animal direcionadas à comparação de metodologias de avaliação genética, foi avaliado o comportamento da variância genética aditiva de populações selecionadas e não selecionadas, por seis gerações sucessivas, via simulação Monte Carlo. Por meio de um modelo genético aditivo, foram simuladas populações de 40 animais (20 machos e 20 fêmeas), sob seleção e acasalamento aleatório. Da geração zero até a quinta geração notou-se na população selecionada uma redução de 44,4 por cento na variância genética aditiva, devido a um aumento de 11,58 por cento no coeficiente de endogamia. Na população não selecionada a redução da variância genética aditiva foi menor (27,46 por cento) em relação à população selecionada, também devido a aumento de 10,26 por cento no coeficiente de endogamia.

The additive genetic variance in selected and unselected populations was evaluated in six successive generations via Monte Carlo simulation. The aim was to build a data system to help researches compare genetic evaluation methodologies in Animal Breeding. By means of an additive genetic model, populations of 40 individuals (20 males and 20 females) were simulated, under selected and random mating system. From the generation zero until the fifth generation, the selected population showed reduction of 44.4 percent in additive genetic variance due to an increase of 11.58 percent in inbreeding coefficient. In the unselected population the reduction in additive genetic variance was lower (27.46 percent) in relation to the selected population, due to the increasing of 10.26 percent in inbreeding coefficient.

Molecular and genetic analyses of flower homeotic genes of Arabidopsis.

Recent genetic and molecular analyses using Arabidopsis has revealed basic mechanisms of floral pattern formation. Here is outlined a genetic model of flower morphogenesis. This shows that combinations of floral organ identity genes direct the organ type and the place in the flower bud. After molecular cloning of these genes, the hypothesis is supported at the molecular level.Molecular analyses of homologous genes from other plants show the same system of flower morphogenesis is shared widely among distantly related species.