Home About us Contact
|
Home About us Contact | ||
|
|
||
Complex Region (complex + region)
Selected AbstractsLRRN6A/LERN1 (leucine-rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2003Laura Carim-Todd Abstract Human chromosome 15q24-q26 is a very complex genomic region containing several blocks of segmental duplications to which susceptibility to anxiety disorders has been mapped (Gratacos et al., 2001, Cell, 106, 367,379; Pujana et al., 2001, Genome Res., 11, 98,111). Through an in silico gene content analysis of the 15q24-q26 region we have identifie1d a novel gene, LRRN6A (leucine-rich repeat neuronal 6A), and confirmed its location to the centromeric end of this complex region. LRRN6A encodes a transmembrane leucine-rich repeat protein, LERN1 (leucine-rich repeat neuronal protein 1), with similarity to proteins involved in axonal guidance and migration, nervous system development and regeneration processes. The identification of homologous genes to LRRN6A on chromosomes 9 and 19 and the orthologous genes in the mouse genome and other organisms suggests that LERN proteins constitute a novel subfamily of LRR (leucine-rich repeat)-containing proteins. The LRRN6A expression pattern is specific to the central nervous system, highly and broadly expressed during early stages of development and gradually restricted to forebrain structures as development proceeds. Expression level in adulthood is lower in general but remains stable and significantly enriched in the limbic system and cerebral cortex. Taken together, the confirmation of LRRN6A's expression profile, its predicted protein structure and its similarity to nervous system-expressed LRR proteins with essential roles in nervous system development and maintenance suggest that LRRN6A is a novel gene of relevance in the molecular and cellular neurobiology of vertebrates. [source] Characterization of site I of human serum albumin using spectroscopic analyses: Locational relations between regions Ib and Ic of site IJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2004Keishi Yamasaki Abstract Site I of human serum albumin is an important and complex region for high-affinity binding of drugs. Equilibrium dialysis showed independent binding of dansyl- L -asparagine (DNSA) and n -alkyl p -aminobenzoates (p -ABEs) to regions Ib and Ic, respectively, in the pH range 6.0,9.0. However, individual binding of DNSA increased with pH in the same range. Binding of the four n -alkyl p -ABEs strongly perturbed the circular dichroism spectrum of bound DNSA, and the effect increased with concentration and the number of carbon atoms in the alkyl moiety. A similar effect was observed by increasing pH from 6.0 to 9.0, a pH range in which human serum albumin is known to undergo the neutral-to-base transition. The spectral changes propose spatial orientation changes of DNSA at region Ib. This proposal was supported by increased fluorescence anisotropy values: n -alkyl p -ABEs binding and the pH-dependent conformational change each restricted the mobility of the naphthalene ring of bound DNSA. Despite the similar effects on the spatial orientation of DNSA, clear differences were observed between the effects of n -alkyl p -ABEs and neutral-to-base transition. The former hardly changed the affinity and maximum fluorescence emission wavelength of bound DNSA; in contrast, the latter significantly affected them. The results give new information about site I and, according to our knowledge, represent a new type of ligand interaction, because the binding site of DNSA could be changed by simultaneous binding of the n -alkyl p -ABEs without affecting the binding constant. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:3004,3012, 2004 [source] Gene expression microarray analysis and genome databases facilitate the characterization of a chromosome 22 derived homogenously staining regionMOLECULAR CARCINOGENESIS, Issue 1 2004Suzanna L. Arcand Abstract Karyotype and fluorescence in situ hybridization (FISH) analyses previously identified a homogenously staining region (HSR) derived from chromosome 22 in OV90, an epithelial ovarian cancer (EOC) cell line. Affymetrix® expression microarrays in combination with the UniGene and Human Genome Browser databases were used to identify the candidate genes comprising the amplicon of the HSR, based on comparison of expression profiles of OV90, EOC cell lines lacking HSRs and primary cultures of normal ovarian surface epithelial (NOSE) cells. A group of probe sets displaying a minimum 3-fold overexpression with a high reliability score (P-call) in OV90 were identified which represented genes that mapped within a 1,2 Mb interval on chromosome 22. A large number of probe sets, some of which represent the same genes, displayed no evidence of overexpression and/or low reliability scores (A-call). An investigation of the probe set sequences with the Affymetrix® and Sanger Institute Chromosome 22 Group databases revealed that some of the probe sets displaying discordant results for the same gene were complementary to intronic sequences and/or the antisense strand. Microarray results were validated by RT-PCR. Genomic analysis suggests that the HSR was derived from the amplification of a 1.1 Mb interval defined by the chromosomal map positions of ZNF74 and Hs.372662, at 22q11.21. The deduced amplicon is derived from a complex region of chromosome 22 that harbors low-copy repeats (LCRs). The amplicon contains 18 genes as likely targets for gene amplification. This study illustrates that large-scale expression microarray analysis in combination with genome databases is sufficient for deducing target genes associated with amplicons and stresses the importance of investigating probe set design before engaging in validation studies. © 2004 Wiley-Liss, Inc. [source] Macaques in farms and folklore: exploring the human,nonhuman primate interface in Sulawesi, IndonesiaAMERICAN JOURNAL OF PRIMATOLOGY, Issue 10 2010Erin P. Riley Abstract The island of Sulawesi is an ecologically diverse and anthropogenically complex region in the Indonesian archipelago; it is home to multiple macaque species and a key locus of human,nonhuman primate interconnections. Here, we review the ethnoprimatology of Sulawesi by exploring two primary domains of the human,macaque interface: overlapping resource use and cultural perceptions of macaques. Crop raiding is the primary form of overlapping resource use. While the raiding of cacao plantations predominates in Central and South Sulawesi, subsistence crops (e.g., sweet potato and maize) are most vulnerable on Buton, Southeast Sulawesi. Despite this overlap levels of conflict are generally low, with farmers showing considerable tolerance. This tolerance can be explained by positive perceptions of the macaques despite their crop raiding behavior, and the finding that in some areas macaques figure prominently in local folklore, hence affording them protection. These findings provide some hope for the future management and conservation of these endemic macaques. Am. J. Primatol. 72:848,854, 2010. © 2010 Wiley-Liss, Inc. [source] Detection of arthritis-susceptibility loci, including Ncf1, and variable effects of the major histocompatibility complex region depending on genetic background in ratsARTHRITIS & RHEUMATISM, Issue 2 2009Carola Rintisch Objective To characterize the arthritis-modulating effects of 3 non,major histocompatibility complex (MHC) quantitative trait loci (QTLs) in rat experimental arthritis in the disease-resistant E3 strain, and to investigate the disease-modulating effects of the MHC region (RT1) in various genetic backgrounds. Methods A congenic fragment containing Ncf1 along with congenic fragments containing the strongest remaining loci, Pia5/Cia3 and Pia7/Cia13 on chromosome 4, were transferred from the arthritis-susceptible DA strain into the background of the completely resistant E3 strain. The arthritis-regulatory potential of the transferred alleles was evaluated by comparing the susceptibility to experimental arthritis in congenic rats with that in E3 rats. The RT1u haplotype from the E3 strain was transferred into the susceptible DA strain (RT1av1), and various F1 and F2 hybrids were generated to assess the effects of RT1 on arthritis susceptibility. Results The DA allele of Ncf1 did not break the arthritis resistance of the E3 rats, although it led to enhanced autoimmune B cell responses, as indicated by significantly elevated levels of anticollagen antibodies in congenic rats. Introgressing Pia5 and Pia7 loci on chromosome 4 broke the resistance to arthritis, and the MHC locus on chromosome 20 in DA rats enhanced arthritis when RT1 interacted with E3 genes. Conclusion The findings in these congenic lines confirm the existence of 3 major QTLs that regulate the severity of arthritis and are sufficient to induce the transformation of a completely arthritis-resistant rat strain into an arthritis-susceptible strain. This study also reveals a dramatic difference in the arthritis-regulatory potential of the rat MHC depending on genetic background, suggesting that strong epistatic interactions occur between MHC and non-MHC genes. [source] Different patterns of associations with anti,citrullinated protein antibody,positive and anti,citrullinated protein antibody,negative rheumatoid arthritis in the extended major histocompatibility complex regionARTHRITIS & RHEUMATISM, Issue 1 2009Bo Ding Objective To identify additional variants in the major histocompatibility complex (MHC) region that independently contribute to risk in 2 disease subsets of rheumatoid arthritis (RA) defined according to the presence or absence of antibodies to citrullinated protein antigens (ACPAs). Methods In a multistep analytical strategy using unmatched as well as matched analyses to adjust for HLA,DRB1 genotype, we analyzed 2,221 single-nucleotide polymorphisms (SNPs) spanning 10.7 Mb, from 6p22.2 to 6p21.31, across the MHC. For ACPA-positive RA, we analyzed samples from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) and the North American Rheumatoid Arthritis Consortium (NARAC) studies (totaling 1,255 cases and 1,719 controls). For ACPA-negative RA, we used samples from the EIRA study (640 cases and 670 controls). Plink and SAS statistical packages were used to conduct all statistical analyses. Results A total of 299 SNPs reached locus-wide significance (P < 2.3 × 10,5) for ACPA-positive RA, whereas surprisingly, no SNPs reached this significance for ACPA-negative RA. For ACPA-positive RA, we adjusted for known DRB1 risk alleles and identified additional independent associations with SNPs near HLA,DPB1 (rs3117213; odds ratio 1.42 [95% confidence interval 1.17,1.73], Pcombined = 0.0003 for the strongest association). Conclusion There are distinct genetic patterns of MHC associations in the 2 disease subsets of RA defined according to ACPA status. HLA,DPB1 is an independent risk locus for ACPA-positive RA. We did not identify any associations with SNPs within the MHC for ACPA-negative RA. [source] | |||||||||||||