Expressions of long non-coding RNA CASC11 and proto-oncogene c-myc in colorectal cancer and their correlation with recurrence and metastasis / 肿瘤研究与临床

Objective:To investigate the expressions of long non-coding RNA (lncRNA) CASC11 and proto-oncogene c-myc in colorectal cancer and their correlation with recurrence and metastasis.Methods:The cancer tissues and paracancerous tissues of 90 colorectal cancer patients in Tangshan Union Medical College Hospital of Hebei Province from February 2016 to July 2018 were collected. Normal colon epithelial cell lines CCD841 and colorectal cancer cell lines SW480, SW620, HCT116, HT29, DLD-1 were cultured in vitro. Separated by the average value of relative expression level of CASC11 or c-myc mRNA in cancer tissues, patients were divided into the high expression and low expression of CASC11 or c-myc. The protein expressions of CASC11 and c-myc mRNA and c-myc were detected by using real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot. Cell lines with the highest protein expressions of CASC11, c-myc mRNA and c-myc were used to do the subsequent experiments. The association of the expression levels of CASC11 and c-myc mRNA with the clinicopathological features was analyzed. Pearson correlation test was used to analyze the relationship between CASC11 and c-myc mRNA of cancer tissues. JASPAR software was used to analyze whether there were binding sites of CASC11 and c-myc gene. The wild-type and mutant-type CASC11 recombinant plasmids were constructed, and the relationship between c-myc and CASC11 was confirmed by using dual luciferase reporter gene assay. Cell lines with the highest expressions of CASC11 and c-myc were transfected with c-myc interference sequence plasmid (Sh-c-myc group) or the negative control sequence plasmid (Sh-NC group), and the conventional cultured blank control group (NC group). The proliferation of cells was detected by using methyl thiazolyl tetrazolium (MTT) method, the invasion and migration abilities of cells were detected by using Tanswell test, and the protein expressions of CASC11, c-myc mRNA and c-myc in cells of all groups were detected by using qRT-PCR and Western blot.Results:The protein expression levels of CASC11, c-myc mRNA and c-myc protein in cancer tissues were increased compared with those in paracancerous tissues, and the differences were statistically significant (all P < 0.05). Compared with CCD841 cells, the protein expression levels of CASC11, c-myc mRNA and c-myc in all colorectal cancer cell lines were increased, and the differences were statistically significant (all P < 0.05); the highest protein expressions of CASC11, c-myc mRNA and c-myc were found in SW480 cell lines which were used to do the subsequent experiments. Pearson correlation analysis showed that there was a positive correlation between CASC11 mRNA and c-myc mRNA in cancer tissues ( r = 0.494, P < 0.05). The high expression rate of CASC11 and c-myc mRNA in cancer tissues for patients with lymph node metastasis was higher than that for those without lymph node metastasis [73.7% (28/38) vs. 26.9% (14/52), 84.2% (32/38) vs. 23.1% (12/52)], the high expression rate of CASC11 and c-myc mRNA in cancer tissues for patients with TNM stage Ⅲ-Ⅳ was higher than that for those with TNM stage Ⅰ-Ⅱ [76.0% (38/50) vs. 10.0% (4/40), 72.0% (36/50) vs. 20.0% (8/40)], and the differences were statistically significant (all P < 0.05). JASPAR software showed that the binding sites were detected in CASC11 promoter region and c-myc gene; dual luciferase reporter gene assay results showed that the relative activity of SW480 cells co-transfected with Sh-c-myc and wild-type CASC11 plasmid was lower compared with that of SW480 cells co-transfected with Sh-NC and wild-type CASC11 plasmid ( P < 0.05). Compared with NC group and Sh-NC group, the expression level of CASC11 mRNA, the number of invasive and migratory cells of SW480 cells in Sh-c-myc group were decreased, while cell proliferation inhibition rate was increased, and the differences were statistically significant (all P < 0.05). Conclusions:CASC11 and c-myc mRNA are highly expressed in colorectal cancer tissues and cell lines, and binding sites can be detected in CASC11 promoter region and c-myc gene. The expressions of both have a correlation, and the down regulation of c-myc can inhibit the invasion and migration of colorectal cancer cells by inhibiting the expression of CASC11.

Estimate of the Association of IGF-I and IGFALS Genes with Growth Traits in Hamdani Sheep

Abstract IGF-I and IGFALS play a vital stimulator role in skeletal growth, cell differentiation, metabolism, and other physiological processes. A total of 65 (male and female) animals were used in the study. Animals were measured for growth traits at birth weight, weaning weight, and weights at 6 months. The average daily gain (ADG) was calculated from birth to weaning (ADG1) and from birth to 6th month (ADG2). PCR-RFLP analysis was used to detect IGF-I polymorphism at the 5' regulatory region and IGFALS at Exon 1. Three genotypes (AA, AB and BB) were observed for IGF-I/BfoI locus with allele and genotype frequency 0.79(A) and 0.21(B); 0.71(AA), 0.15(AB) and 0.14(BB). Also, three genotypes (AA, AB and BB) were found for IGFALS/HinfI site with allele and genotype frequency as 0.22(A) and 0.78(B); 0.11(AA), 0.23(AB) and 0.66(BB). The genes were in agreement with Hardy-Weinberg equilibrium (p>0.05). Association analysis suggested that IGF-I and IGFALS significantly affected the growth traits (P<0.05). In terms of birth weight, The AA genotypes of IGF-I were higher than AB and BB. The AB genotype in terms of IGF-I had higher ADG2 compared with other genotypes. The AA genotype of the IGFALS gene was higher in terms of birth weight than other genotypes. In addition, the BB genotype was higher ADG1 than AA and BB. It is suggested that polymorphism of the IGF-I and IGFALS genes may be a potential molecular marker for growth traits in Hamdani sheep.

Genomic marker assisted identification of genetic loci and genes associated with variation of grain zinc concentration in rice

A study was conducted to examine the genetic divergence and to determine the genetic loci and genes associated with natural variation of grain zinc (Zn) concentration among 28 landraces, improved varieties and advanced breeding lines of rice using candidate gene specific primers. Field evaluation of the experimental material was conducted in randomized block design with three replications and Zn content in unpolished grains of the entries was determined by addition of nitric acid and perchloric acid (1:3) following the procedure ofdiacid digestion method. Statistical analysis revealed the exploitable extent of variability with respect to grain Zn concentration among the entries. Eighteen entries were selected from the two extremes of grain Zn distribution range and subjected to molecular profiling using a panel of 14 candidate genes specific 12 reported and 14 designed primer pairs. Only eight (OsZIP1-1, OsZIP3a, OsZIP4a, OsZIP5-3, OsZIP7-2, OsZIP8b, OsNRAMP7 and OsNAAT1) reported and eight (OsZIP3K, OsZIP4K, OsZIP5K, OsZIP7K, OsNRAMP7K, OsNAAT1K, OsNACK and OsYSL14K) designed primers generated polymorphic amplified products showing sequence length variation due to targeted amplification of candidate genes specific genomic regions. Ample genetic differentiation and divergence were revealed among the entries, which were accommodated into similarity coefficient-based six clusters, remarkably consistent with grain Zn concentrationof the entries. Hierarchical classification pattern of entries was almost completely corroborated by principal co-ordinate analysisbased spatial distribution pattern of their genetic profiles. Molecular analysis based on candidate genes specific primers appeared to be an efficient approach for the elucidation of genetic differentiation and divergence in relation to variation of grain Zn concentration among entries. Hence, these markers can be effectively and efficiently utilized for grain Zn concentration related discrimination of rice genotypes and selection of parental genotypes for grain Zn biofortification. Microsatellites were detected within the candidate genes and amplicons, thereby providing a basis to deduce that the repeat sequence length variation in candidate genes may be a role player in the differential grain Zn accumulation in rice varieties. Single marker analysis established the association of OsNACK, OsZIP1-1, OsNRAMP7 and OsNRAMP7K with grain Zn concentration. Thus, these four markers can be effectively used in marker-assisted selection programme for grainZn biofortification in rice.

The Research Progress of Essential Hypertension Related Gene DNA Methylation / 现代生物医学进展

Hypertension is a common and chronic disease,and is also the mainly risk factor of cardio-cerebrovascular disease.Essential hypertension is a complex disease caused by the common function of multiple genes and environmental factors,but the exact pathogenesis is still unclear.With the study continues,the role of DNA methylation and other epigenetic factors in pathological process with essential hypertension (EH) gradually be taken seriously.This review summarizes the research progress of some essential hypertension related methylation genes' function in the course of hypertension,to explain the relationship between DNA methylation markers which can be influenced by environment factor and essential hypertension and help us have a further understanding about the hypertension pathogenesis.

Recent advances in genetic study on high myopia / 眼科新进展

High myopia is a common blinding eye disease with high specificity and population genetic heterogeneity.It has emerged as a major public health concern,which is often accompanied by many severe associated comorbidities,including retinal detachment,cataract and glaucoma.While rarely effective treatment Is found so far.This article reviews recent advances in understanding genetic mechanism of high myopia,such as mode of inheritance,MYP locus and candidate genes.

Up-regulation of NLRC5 and NF-кB signaling pathway in carrier chickens challenged with Salmonella enterica Serovar Pullorum at different persistence periods.

The immune performance, SNPs and expression levels of candidate genes (IL1-β, Nramp1, TLR4, MyD88, NF-кB and NLRC5) were analyzed in carrier chickens of a Chinese indigenous breed infected with Salmonella enterica Serovar Pullorum at different persistence periods (12, 19 and 24 weeks of age). Carrier birds at 19 weeks of age presented significant difference in most immune parameters, as compared to carriers at 12 and 24 weeks of age, while no significant difference in most immune parameters was observed between carriers at 12 and 24 weeks of age. The genotype distributions of IL1-β and TLR4 presented significant differences between carriers and healthy birds. The expression levels of most candidate genes in carriers at 19 weeks of age were significantly higher than that in carriers at 12, 24 weeks of age and healthy birds and reached 1% level of significance between carriers at 19 weeks of age and healthy birds. The expression patterns of all genes, but IL-1β and NLRC5 between carriers at 12 and 24 weeks of age in all tissues were similar. Compared with carriers at 12 weeks of age, IL1-β was significantly down-regulated, but NLRC5 was significantly up-regulated in carriers at 24 weeks of age. Our study demonstrated that immune performance of carrier birds was severely impaired at age of sexual maturation and NLRC5 might play as a negative mediator of NF-кB pathway involved in immune response to asymptomatic infection by S. Pullorum. The TLR4/MyD88/NF-кB pathway might be suitable for study on S. Pullorum infection in Chinese indigenous breeds.

Bioinformatics analysis of biomarkers and transcriptional factor motifs in Down syndrome

In this study, biomarkers and transcriptional factor motifs were identified in order to investigate the etiology and phenotypic severity of Down syndrome. GSE 1281, GSE 1611, and GSE 5390 were downloaded from the gene expression ominibus (GEO). A robust multiarray analysis (RMA) algorithm was applied to detect differentially expressed genes (DEGs). In order to screen for biological pathways and to interrogate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, the database for annotation, visualization, and integrated discovery (DAVID) was used to carry out a gene ontology (GO) function enrichment for DEGs. Finally, a transcriptional regulatory network was constructed, and a hypergeometric distribution test was applied to select for significantly enriched transcriptional factor motifs. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were each up-regulated two-fold in Down syndrome samples compared to normal samples; of these, SON and TTC3 were newly reported. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were located on human chromosome 21 (mouse chromosome 16). The DEGs were significantly enriched in macromolecular complex subunit organization and focal adhesion pathways. Eleven significantly enriched transcription factor motifs (PAX5, EGR1, XBP1, SREBP1, OLF1, MZF1, NFY, NFKAPPAB, MYCMAX, NFE2, and RP58) were identified. The DEGs and transcription factor motifs identified in our study provide biomarkers for the understanding of Down syndrome pathogenesis and progression.

Advances in molecular genetic study of primary open angle glaucoma / 中华实验眼科杂志

Primary open angle glaucoma (POAG) is a group of disorders characterized by loss of retinal ganglion cells (RGCs) associated with optic nerve degeneration and visual field damage.With the application of molecular biology in ophthalmology,at least 20 chromosome loci have been identified to be linked to POAG.Only 3 causative genes were identified from these loci,i.e.myocilin (MYOC),optineurin (OPTN) and WD repeat domain 36 (WDR36),which altogether account for less than 10％ of POAG.Only a portion of POAG Complies with Mendelian inheritance,and a considerable fraction results from a large number of variants in multiple genes,each contributing less effects.The main technological approaches include family linkage analysis,genome-wide scan,casecontrol association study,etc.Association studies found at least 16 genes to be related to POAG,but reports on glaucoma-causing effects of these genes are conflicting.In this article,we reviewed the POAG related genes,especially the four well known causative genes of MYOC,OPTN,WDR36,and CA V1/CA V2,in terms of their locations,structures,functions,and mutations.

Progress in single nucleotide polymorphism with cancer susceptibility and its clinical application / 中华检验医学杂志

Single nueleotide polymorphisms (SNPs) are the most common genetic variants in human genome.Candidate gene,genome-wide association studies (GWASs) and exome sequencing which base on SNPs have made a great progress in identifying cancer susceptibility.The development and application of high resolutions in SNPs has played an important role in clarifying the mechanism,prevention,diagnosis and targeted therapy in cancers.

Syndecan-4 is a candidate gene for diabetic nephropathy / 中华肾脏病杂志

Objective To identify the candidate genes in the vicinity of a susceptibility locus (urinary albumin 1,UA-1) contributing to the development of albuminuria in type 2 diabetic KK/Ta mice. Methods Total RNA was extracted from the kidneys of KK/Ta (n=3) and BALB/c (n=2) mice at 20 weeks of age.The gene expression profile in kidney was investigated using the Affymetrix Murine Genome U74Av2 array.Competitive RT-PCR was used to confirm the differential expression of syndecan-4 which located in the vicinity of UA-1.Genome DNA was extracted from KK/Ta and BALB/c mice.DNA sequence analysis of the coding and promotor region of syndecan-4 gene was conducted. Results In the vicinity of the susceptibility locus (UA-1)contributing to the development of albuminuria in type 2 diabetic KK/Ta mice,10 candidate genes that showed differential expression were identified.Among them,the gene expression of syndecan-4in KK/Ta kidneys at 20 weeks of age was up-regulated by 26.1 times of age-matched BALB/c kidneys.Sequence analysis revealed two synonymous polymorphisms in the coding region (A93C and T216C) and three polymorphisms in the promoter region (-T263C,-T396C and -G669A) of the syndecan-4 gene.The TATA box was found at 321 bp upstream from the transcription start site,and the T263C polymorphism was located in the binding site of transcription factor Clox.Conclusions Syndecan-4 gene is mapped in the vicinity of the susceptibility locus contributing to the development of albuminuria in type 2 diabetes.The gene expression of syndecan-4 in KK/Ta kidneys is up-regulated than that in age-matched BALB/c kidneys at 20 weeks of age.Thus syndecan-4 may be one of the potential candidate genes responsible for diabetic nephropathy.Sequence differences in the promoter region influence the expression levels of syndecan-4 genes in KK/Ta kidneys.

A two-step genetic study on quantitative precursors of coronary artery disease in a homogeneous Indian population: Case–control association discovery and validation by transmission-disequilibrium test.

In spite of its strong familiality, gene identification for coronary artery disease (CAD) has not yielded a consistent picture. One major reason for this is that families or cases and controls were not recruited from a homogeneous population. We, therefore, attempted to map genes underlying 10 quantitative traits (QTs) that are known precursors of CAD in a homogeneous population (Marwari) of India. The QTs are apolipoprotein B (ApoB), C-reactive protein (CRP), fibrinogen (FBG), homocysteine (HCY), lipoprotein (a) (LPA), cholesterol – total (CHOL-T), cholesterol – HDL (CHOL-H), cholesterol – LDL (CHOL-L), cholesterol – VLDL (CHOL-V) and triglyceride (TG). We assayed 209 SNPs in 31 genes among members of Marwari families. After log-transformation and covariate-adjustment of the QTs, a two-step analysis was performed. In Step-1, data on unrelated individuals were analysed for association with the SNPs. In Step-2, for validation of Step-1 results, a quantitative transmission-disequilibrium test on parent– offspring data was performed for each SNP found to be significantly associated with a QT in Step-1 on an independent sample set drawn from the same population. Statistically significant results found for the various QTs and SNPs were: rs3774933, rs230528, rs230521, rs1005819 and rs1609798 (intronic, NFKB1) with APOB; rs5361 (Missense, R>S, SELE) and rs4648004 (Intronic, NFKB1) with FBG; rs4220 (Missense, K>R, FGB) with HCY; and rs3025035 (Intronic, VEGFA) with CHOL-H. SNPs in SELE, VEGFA, FGB and NFKB1 genes impact significantly on levels of quantitative precursors of CAD in Marwaris.

Genomic approaches to coronary artery disease.

Coronary artery disease (CAD) is a leading cause of death and disability worldwide. In addition to lifestyle and environmental factors which are major aetiologic determinants, there is considerable familial clustering of the disease indicating a genetic component in its causation. Although the total genetic contribution to CAD risk can be quantified, the determination of the size and number of contributing effects is impossible without identifying all CAD susceptibility genes. However, despite extensive studies, strong evidence of a molecular genetic association with coronary artery disease or myocardial infarction remains elusive. Genome wide association studies have been successful in identifying robust associations of single nucleotide polymorphisms (SNP) with CAD. Identifying the causal variant and dissecting pathways linking these variants to disease process is a major challenge. Technologies from whole genome sequencing, proteomics, transcriptomics and metabolomics are now available to extend analysis to a more complete range of potential susceptibility variants, and to support more explicit modelling of the joint effects of genes and environment. The availability of these high throughput technologies does not diminish the importance of rigorous phenotyping and appropriate study designs in all the endeavours to understand the aetiopathogenesis of CAD. Combining classical epidemiology with modern genomics will require collaborative efforts within the cardiovascular disease community at both bench and bedside and this will have the potential to expand our understanding of CAD and translate discoveries into clinically useful applications that will have a major impact on public health.

EFFECTS OF HABITUAL EXERCISE AND CANDIDATE GENE POLYMORPHISMS RELATED TO BONE ON CALCANEAL QUANTITATIVE ULTRASOUND IN MIDDLE-AGED AND ELDERLY JAPANESE / 体力科学

The purpose of this study was to investigate the interaction of habitual exercise and candidate gene polymorphisms related to bone on osteo sono-assessment index (OSI) by quantitative ultrasound (QUS) in middle-aged and elderly Japanese. Participants were classified into exercise group (E; n=172, 62.3 ± 7.7 yr) and sedentary group (S; n=65, 58.6 ± 9.2 yr). The OSI was measured with AOS-100. DNA was extracted from blood, and single nucleotide polymorphism in vitamin D receptor, estrogen receptor α, and transforming growth factor-βI were genotyped by TaqMan assay. Group E had significantly lower body weight and body mass index (BMI) than Group S. In men, although Group E was older than Group S, Group E had significantly higher OSI rather than Group S. There was no significant interaction between habitual exercise and each gene polymorphism on OSI. These results essentially remained unchanged even when analysis of covariance was applied after adjustment for age, body weight, and BMI. These results suggest habitual exercise and genetic factors have no interaction on OSI in middle-aged and elderly Japanese. Further investigations are needed to prove the interaction of other gene polymorphisms and exercise.

Polymorphisms on SSC15q21-q26 Containing QTL for reproduction in Swine and its association with litter size

Several quantitative trait loci (QTL) for important reproductive traits (ovulation rate) have been identified on the porcine chromosome 15 (SSC15). To assist in the selection of positional candidate swine genes for these QTL on SSC15, twenty-one genes had already been assigned to SSC15 in a previous study in our lab, by using the radiation hybrid panel IMpRH. Further polymorphism studies were carried out on these positional candidate genes with four breeds of pigs (Duroc, Erhualian, Dahuabai and Landrace) harboring significant differences in reproduction traits. A total of nineteen polymorphisms were found in 21 genes. Among these, seven in six genes were used for association studies, whereby NRP2 polymorphism was found to be significantly (p < 0.05) associated with litter-size traits. NRP2 might be a candidate gene for pig-litter size based on its chromosome location (Du et al., 2006), significant association with litter-size traits and relationships with Sema and the VEGF super families.

Bovine gene polymorphisms related to fat deposition and meat tenderness

Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP), thyroglobulin (TG) and diacylglycerol O-acyltransferase (DGAT1). A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus), Canchim (5/8 Bos taurus + 3/8 Bos indicus), Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus), Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus) and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus) breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM) procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus.

Growth hormone 1 gene (GH1) polymorphisms as possible markers of the production potential of beef cattle using the Brazilian Canchim breed as a model

The growth hormone 1 gene (GH1) is a candidate gene for body weight and weight gain in cattle since it plays a fundamental role in growth regulation. We investigated the GH1 gene AluI and DdeI restriction enzyme polymorphisms, located 149 bp apart in the cattle genome, as possible markers of the production potential of Canchim crossbreed cattle, a 5/8 Charolais (Bos taurus) and 3/8 Nelore (Bos indicus) breed developed in Brazil, by evaluating the birth weight, weaning weight, yearling weight and plasma insulin-like growth factor-1 (IGF-1) concentration of 7 month to 10 months old Canchim calves (n = 204) of known genealogy and which had been genotyped for the AluI and DdeI markers. Our results showed significant effect (p < 0.05) between the homozygous DdeI+/DdeI+ polymorphism and the estimated breeding value for weaning weight (ESB-WW), while the AluI leucine homozygous (L/L) and leucine/valine (L/V) heterozygous polymorphisms showed no significant effect on the traits studied. The restriction sites of the two enzymes led to the formation of haplotypes which also exerted a significant effect (p < 0.05) on the ESB-WW, with the largest difference being 8.5 kg in favor of the homozygous L plus DdeI+/L plus DdeI+ genotype over the heterozygous L plus DdeI-/V plus DdeI+ genotype.

Allelic variants of DYX1C1 are not associated with dyslexia in India.

Dyslexia is a hereditary neurological disorder that manifests as an unexpected difficulty in learning to read despite adequate intelligence, education, and normal senses. The prevalence of dyslexia ranges from 3 to 15% of the school aged children. Many genetic studies indicated that loci on 6p21.3, 15q15-21, and 18p11.2 have been identified as promising candidate gene regions for dyslexia. Recently, it has been suggested that allelic variants of gene, DYX1C1 influence dyslexia. In the present study, exon 2 and 10 of DYX1C1 has been analyzed to verify whether these single nucleotide polymorphisms (SNPs) influence dyslexia, in our population. Our study identified 4 SNPs however, none of these SNPS were found to be significantly associated with dyslexia suggesting DYX1C1 allelic variants are not associated with dyslexia.

Association of the heart fatty acid-binding protein gene with quality of carcass and meat traits in pigs / Associação entre o gene da proteína de ligação de ácidos graxos - coração com características de carcaça e qualidade da carne em suínos

The heart fatty acid-binding protein (HFABP) gene was sequenced in parental animals of a F2 crossing of boars of the Brazilian native Piau breed with commercial sows (Landrace x Large White Pietrain). Primers used for PCR were designed to amplify four exons of the gene. The PCR products were sequenced and compared with the GenBank sequences. Differences between the generated sequences and the GenBank sequences were observed for both genetic groups. A total of 246 F2 animals were genotyped using the Hinf I restriction enzyme. Two genotypes were identified, 198 being animals HH and 48 Hh. The Hinf I SNP was significantly associated with weights of loin (bone-in) (P<0.05), jowl (P<0.05), sirloin (P<0.10), and kidneys (P<0.01). These results showed the potential of the H-FABP gene in marker-assisted selection programs for carcass traits in pigs.

O gene da proteína de ligação de ácidos graxos - coração foi seqüenciado em animais parentais de um cruzamento F2 entre varrões da raça nativa brasileira Piau e fêmeas comerciais (Landrace x Large White x Pietrain). Os primers utilizados na reação em cadeia da polimerase foram desenhados para amplificarem os quatro éxons do gene. Os fragmentos amplificados foram seqüenciados e comparados com a seqüência do gene depositada no GenBank. Foram observadas divergências entre as seqüências geradas e as do GenBank para ambos os grupos genéticos. Foram genotipados 246 animais F2 utilizando-se a enzima Hinf I. Dois genótipos foram identificados, sendo 198 animais HH e 48 animais Hh. O polimorfismo apresentou efeito sobre o peso total do carré (P<0,05), o peso da papada (P<0,05), o peso do filezinho (P<0,10) e o peso dos rins (P<0,01). Os resultados indicam que o gene da H-FABP apresenta potencial para aplicação em programas de seleção assistida por marcadores moleculares em suínos.

Common Gene Expression Pattern in the Rat Brain Induced by Several Mood: Stabilizing Drugs / 대한정신약물학회지

OBJECTIVE: This study sought to identify candidate genes related to the clinical effects of several mood stabilizers through gene expression profiles using microarrays and real time RT-PCR. METHOD: Rats were treated with lithium carbonate, valproate, or clozapine for 10 days. Total RNA was extracted from the rat brains and used for microarray analysis. Of 54 genes showing more than 1.5-fold changes induced by all three mood stabilizers, seven genes were selected, and drug-induced changes in gene expression were confirmed by real time RT-PCR. In addition, genotype distribution of the GRIK2 gene was compared between 181 patients with bipolar disorder and 350 normal controls. RESULTS: Of the seven candidate genes, GRIK2 and PRKAR were confirmed as being downregulated by lithium and valproate. However, none of the genes was affected by all three drugs. The allele and genotype distribution in two SNPs of GRIK2 did not differ between the patient and control groups. CONCLUSIONS: Although this study demonstrated overall negative results, the present findings will be used in future studies for establishing various mechanisms of mood stabilizers.

El gen receptor a dopamina D4 y su asociación con los trastornos mentales / DRD4 polymorphysm and the association with mental disorders

The dopamine D4 receptor (DRD4) is the most important gene in psychiatric genetics since its involvement in the physiology of behavior, pharmacology response and psychopathology. DRD4's sequence gene present some polymorphism such as in the exon 3 constituted from 2 to 10 copies of repetitive sequences of 48 base pair (bp), from class variable number tandem repeats (VNTR). An additional genetic variant in the exon 1 presents polymorphisms to 12 bp VNTR, and the variation -521 C by T of the promoter region. The -521 T alíele can reduce the efficiency of the gene expression in comparison with the C alíele. The DRD4 gene codes a protein transmembranal of 7 domains, distributed in front cortex, striatum, hypothalamus and hippocampus. This review discusses the biological significance of DRD4 gene and its perspective with emphasis on the impact of association studies in some illness mental and behavioral traits. The DRD4 polymorphism has been studied in association with illnesses like schizophrenia, attention deficit hyperactivity disorder (ADHD), obsessive-compulsive with tics, bipolar manic-depressive disorder, in addition behavioral traits such as novelty seeking. The DRD4 gene is a genetic marker that could play a role in etiology of different mental illness, and behavioral traits, and its polymorphism can be used in association studies, epigenetic and pharmacogenomic analysis for help to understand the genetics basis of both mental disorders and traits.

El gen receptor a dopamina D4 (DRD4) ha sido analizado por su estructura, su polimorfismo genético, su constitución proteínica, su distribución neuroanatómica y su respuesta farmacológica. La secuencia del gen DRD4 presenta varios polimorfismos, como del tipo número variable de repetidos en tándem (VNTR) en el exón 3, el VNTR de 12 pares de bases del exón 1 y el polimorfismo único de nucleótidos (SNP) de la región del promotor. El gen DRD4 codifica una proteína transmembranal de 7 dominios, que se distribuye en corteza frontal, en estriado, en hipotálamo y en el hipocampo. Esta revisión discute la importancia biológica del gen DRD4 y sus perspectivas ante nuevas áreas de investigación con énfasis en recientes estudios de asociación en diferentes enfermedades mentales y en comportamientos. El DRD4 es uno de los genes candidatos cuya variación polimórfica ha sido relacionada con algunos trastornos psiquiátricos como esquizofrenia, trastorno de déficit de atención e hiperactividad, obsesivo compulsivo con tics y trastorno por consumo de sustancias, así como con la característica de personalidad de búsqueda de la novedad. El gen DRD4 es un marcador genético y un modelo útil para estudios de asociación, epigenéticos y farmacogenómicos que buscan identificar el origen de trastornos psiquiátricos y comportamientos.