X连锁非特异性精神发育迟滞相关基因功能研究进展

X连锁非特异性精神发育迟滞相关基因是一类目前研究较多的基因,其突变或缺失患者仅具有一般或特殊认知功能障碍的单纯表现型。从生物学功能和认知功能两方面研究X连锁非特异性精神发育迟滞相关基因,不仅对弄清非特异性精神发育迟滞的遗传基础有重要意义,而且还能开拓出研究人类认知功能的分子遗传机理的新领域。文章就目前对X连锁非特异性精神发育迟滞相关基因的生物学功能和认知功能的研究现状,及该研究方向的发展前景进行了综述。      

X连锁精神发育迟滞相关基因JARID1C研究进展

JARID1C基因属于X连锁精神发育迟滞相关基因之一, 其表达产物影响大脑神经系统中相关基因的转录和表达, 并可能与人类认知能力密切相关。对JARID1C基因功能的研究有助于理解该基因在精神发育迟滞形成和人类认知能力发展中的分子作用, 也能为精神发育迟滞的临床诊断和防治提供参考。文章对JARID1C基因的定位、分离、转录产物的生理功能及其认知功能做一综述, 并对以后的研究工作进行了展望。     

与精神发育迟滞有关的IL1RAPL1基因研究进展

IL1RAPL1基因缺失、倒置以及突变会导致非特异性精神发育迟滞,因而与人类认知能力密切相关。研究该基因的生物学功能与认知功能将为临床诊断和防治精神发育迟滞提供参考。本文综述了IL1RAPL1基因产物、基因的生理功能与认知功能的研究现状,并对今后的进一步研究工作进行了展望。     

OPHN1基因的研究进展

OPHN1是X连锁的与非特异性精神发育迟滞有关的基因之一,编码RhoGTP酶激活蛋白（RhoGAP）,包含RhoGTP酶激活结构域和氨基末端结构域,参与调节RhoGTP酶的信号转导过程。它广泛表达于机体神经系统,并被严格调控。基因内的突变会导致精神发育迟滞的发生。对这些非特异性精神发育迟滞相关基因的研究,将有助于揭示智力活动中认知过程的分子基础。     

X连锁非特异性精神发育迟滞相关基因PAK3研究进展

PAK3基因突变会导致非特异性精神发育迟滞, 因而与人类一般和特殊认知能力密切相关。研究该基因的生物学功能和认知功能将为临床诊断和防治由此引起的精神发育迟滞患者提供参考。文章综述了对PAK3基因产物、基因的生物学与认知功能的研究现状, 并对今后的进一步研究工作进行了展望。     

常染色体非特异性精神发育迟滞相关基因研究进展

常染色体上一些基因与神经系统的发育和功能密切相关, 突变后可导致非特异性精神发育迟滞。文章从基因定位、表达、生物学功能与突变后致病机理等方面, 对常染色体非特异性精神发育迟滞相关基因的研究现状进行了综述, 并展望了今后这一领域的研究前景。     

GDI1基因多态性与秦巴山区儿童NSMR及其智力水平的相关性研究

用来自中国中西部秦巴山区的非特异性精神发育迟滞患者及正常对照人群为样本, 通过研究分别位于GDI1基因第7外显子剪接区和第8外显子上的rs2276462和rs11549300两个功能SNP位点的多态性, 探索GDI1基因的多态现象与当地儿童的精神发育迟滞及其智力水平的相关性。在样本人群中仅观察到rs11549300位点的多态现象, 而rs2276462位点在秦巴山区儿童中十分保守。病例-对照分析结果显示, rs11549300位点多态性与秦巴山区儿童的非特异性精神发育迟滞无显著相关性(P>0.05), 但是其多态现象可能与当地儿童的智力水平有一定的相关性(P=0.03), 但是这一结论还需要在更大样本中, 通过选择更多的遗传标记来进一步确证。     

Slit-Robo细胞信号转导通路研究进展

Slit-Robo细胞信号转导通路调控多种多样的生理功能,不同的下游信号转导途径可产生不同的生理功能.其中最广为人知的功能是介导双侧对称生物体胚胎神经系统发育时的轴突排斥现象.近年来,作为一种在生物体内广泛表达的细胞信号转导通路,Slit-Robo的功能库已大大扩展,与神经发育、血管生成、器官及组织发育以及干细胞的增殖...     

花、基因、禾本科

进化发育生物学的一个重要任务就是揭示形态多样性的分子基础,该领域的研究包含形态、形态发育相关基因和形态所属类群等三个要素。花/花序是进化发育生物学研究的首要对象,系统发育重建和个体发育剖析的结合将促进认知花的形态进化。发育相关基因的进化表现为等位基因遗传或表观遗传的突变,基因家族生与死的进化,不同基因组拥有独特的基因。运用形态学或序列分析方法很大程度揭示了禾本科植物花进化过程中的基因进化。试从学科问题、思路方法以及具体例子介绍植物进化发育生物学。     

花、基因、禾本科

进化发育生物学的一个重要任务就是揭示形态多样性的分子基础, 该领域的研究包含形态、形态发育相关基因和形态所属类群等三个要素。花/花序是进化发育生物学研究的首要对象, 系统发育重建和个体发育剖析的结合将促进认知花的形态进化。发育相关基因的进化表现为等位基因遗传或表观遗传的突变, 基因家族生与死的进化, 不同基因组拥有独特的基因。运用形态学或序列分析方法很大程度揭示了禾本科植物花进化过程中的基因进化。试从学科问题、思路方法以及具体例子介绍植物进化发育生物学。     

Molecular basis of X-linked non-specific mental retardation

Mental retardation (MR) is a common disorder, affecting 1-3% of the total population. This condition results from failure to develop cognitive abilities and intelligence level appropriate for the age group. Mental retardation is basically a clinically as well as etiologically heterogeneous type of condition and both genetic and non-genetic factors have been found to be involved. There are more than 1000 entries in Online Mendelian Inheritance in Man (OMIM) database under the name of mental retardation. In recent years 15 genes for X linked non-specific mental retardation have been identified which provide important clues regarding molecular and cellular processes involved in signal transduction cascade in central nervous system. Recent advancements in identification and characterization of X-linked non-specific mental retardation genes have been discussed in this review. Understanding of the molecular pathways of disease causing genes would be helpful in developing effective therapeutic approaches for mental retardation.     

Fruit flies and intellectual disability

Mental retardation - more commonly known nowadays as intellectual disability - is a severe neurological condition affecting 3% of the general population. As a result of analysis of familial cases and recent advances in clinical genetic testing great strides have been made in our understanding of the genetic etiologies of mental retardation. Nonetheless, no treatment is currently clinically available to patients suffering from intellectual disability. Several animal models have been used in the study of memory and cognition. Established paradigms in Drosophila have recently captured cognitive defects in fly mutants for orthologs of genes involved in human intellectual disability. We review here three protocols designed to understand the molecular genetic basis of learning and memory in Drosophila and the genes identified so far with relation to mental retardation. In addition, we explore the mental retardation genes for which evidence of neuronal dysfunction other than memory has been established in Drosophila. Finally, we summarize the findings in Drosophila for mental retardation genes for which no neuronal information is yet available. All in all, this review illustrates the impressive overlap between genes identified in human mental retardation and genes involved in physiological learning and memory.     

Polymorphisms in the <Emphasis Type="Italic">DLG3</Emphasis> Gene is not Associated with Non-Syndromic Mental Retardation in the Chinese Han Population of Qin-Ba Mountain

Discs-large-related 3 (DLG3), a member of the membrane-associated guanylate kinases (MAGUKs) protein family, playing an important role in regulating NMDA signal pathway and contributing to synaptic plasticity, may have an influence on the susceptibility of non-syndromic mental retardation (NSMR). To investigate the possible genetic contribution of DLG3 gene to the NSMR of Chinese Han population, we performed an association study of 556 subjects (118 NSMR, 116 borderline NSMR, and 322 controls in 275 males and 281 females) from Qin-Ba mountain region of Shaanxi province in the northwest of China by five common SNPs in the gene. The results showed that there was no positive association between the genetic variations of DLG3 and NSMR. In conclusion, the results of this study indicated that DLG3 did not associate with NSMR in Chinese Han population; however, further studies are needed.     

Molecular neurobiology of human cognition

Recent studies into human mental retardation syndromes have given new insights into the molecular underpinnings of human cognitive processing, in particular into mechanisms likely to contribute to learning and memory. In this minireview, we present an overview of one signal transduction cascade that has garnered attention of late in this context, the ras/ERK/CREB pathway. We focus on this cascade because of recent exciting discoveries concerning the basis of neurofibromatosis type 1 (NF1) mental retardation, which link cognitive defects in this syndrome to disruptions of ras and its intracellular targets.     

The role of neuronal complexes in human X-linked brain diseases

Beyond finding individual genes that are involved in medical disorders, an important challenge is the integration of sets of disease genes with the complexities of basic biological processes. We examine this issue by focusing on neuronal multiprotein complexes and their components encoded on the human X chromosome. Multiprotein signaling complexes in the postsynaptic terminal of central nervous system synapses are essential for the induction of neuronal plasticity and cognitive processes in animals. The prototype complex is the N-methyl-D-aspartate receptor complex/membrane-associated guanylate kinase-associated signaling complex (NRC/MASC) comprising 185 proteins and embedded within the postsynaptic density (PSD), which is a set of complexes totaling approximately 1,100 proteins. It is striking that 86% (6 of 7) of X-linked NRC/MASC genes and 49% (19 of 39) of X-chromosomal PSD genes are already known to be involved in human psychiatric disorders. Moreover, of the 69 known proteins mutated in X-linked mental retardation, 19 (28%) encode postsynaptic proteins. The high incidence of involvement in cognitive disorders is also found in mouse mutants and indicates that the complexes are functioning as integrated entities or molecular machines and that disruption of different components impairs their overall role in cognitive processes. We also noticed that NRC/MASC genes appear to be more strongly associated with mental retardation and autism spectrum disorders. We propose that systematic studies of PSD and NRC/MASC genes in mice and humans will give a high yield of novel genes important for human disease and new mechanistic insights into higher cognitive functions.     

An association study between IL1RAPL2 gene and non-specific mental retardation in Chinese children

Non-specific mental retardation (NSMR) is one of common children psychiatric diseases with a high prevalence (1–3%). Here we investigated the association between the genetic variants of IL1RAPL2 gene and NSMR in the children of QinBa region of China. We chose five common SNPs of IL1RAPL2, examined their individual genotype frequencies using the conventional polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) method, and evaluated the association between these genetic polymorphisms and NSMR with the suitable biostatistic software. The allele and genotype distributions of two SNPs (rs5962298 and rs9887672) showed significant differences between the control and NSMR groups (allele: p = 0.020 and 0.017; genotype: p = 0.025 for rs9887672 respectively). The distribution differences became more significant in girls, but disappeared in boys, suggesting a gender effect. Taken together, we provide substantial evidence that IL1RAPL2 conferred a NSMR susceptibility to children of Qinba region in China. In future, further work should be carried out to scan mutations and to investigate the specific-gender effect in this gene.     

X-linked non-specific mental retardation

Non-specific mental retardation is a very common and genetically heterogeneous disorder but, to date, only six genes related to this condition have been identified. Five of these six have been found in the past two years, through positional-cloning efforts of mapped X-linked families. The characteristics of the newly identified genes are providing insights into the molecular mechanisms of mental impairment and the development of cognitive functions.