Cleft lip with or without cleft palate (CL/P) is the most frequent craniofacial malformation seen in man. The etiology of CL/P is complex involving both genetic and epigenetic (environmental) factors, and the genes play an almost deterministic role in the normal development of craniofacial structures. This study was aimed at ascertaining the association of HLA microsatellites in CL/P patients.
MATERIALS AND METHODS:
Case DNA was obtained from 76 patients (40M and 36 F, average age 7.8 years, range 1-16 years). Unaffected individuals from the same geographical area without population mixing included as controls (n=154, 76 M and 78 F, average age 8.2 years, range 2-17 years). All DNA samples were purified from peripheral blood by standard techniques.
RESULTS:
Four microsatellites were compared in this case-control study. C1_2_5 locus was the most polymorphic marker with 15 observed alleles while C1_4_1 had the least number of alleles. Three of the four markers viz MIB,C1_4_1 and C1_2_5 showed a significant association of microsatellite alleles with CL/P. Five alleles (MIB_326,332,350; C1_4_1 – 213 and C1_2_5-204) were seen with an increased frequency among the test samples, whereas two alleles (C1-4_1_217, and C1_2_5_196) had an increased frequency among the control samples. One allele (C1-4-1-209) had an increased frequency in patient group but was not observed in the controls.
CONCLUSION:
The role of HLA complex in the pathogenesis of CL/P is speculative and has not been established so far. The result of this study shows that a few alleles have an increased frequency of expression in the diseased group which suggests that these alleles may predispose the individuals to clefting. This finding may be beneficial to aid in early diagnosis and plan intervention strategies. 相似文献
ScPif1 DNA helicase is the prototypical member of a 5′-to-3′ helicase superfamily conserved from bacteria to human and plays various roles in the maintenance of genomic homeostasis. While many studies have been performed with eukaryotic Pif1 helicases, including yeast and human Pif1 proteins, the potential functions and biochemical properties of prokaryotic Pif1 helicases remain largely unknown. Here, we report the expression, purification and biochemical analysis of Pif1 helicase from Bacteroides sp. 3_1_23 (BsPif1). BsPif1 binds to a large panel of DNA substrates and, in particular, efficiently unwinds partial duplex DNAs with 5′-overhang, fork-like substrates, D-loop and flap-like substrates, suggesting that BsPif1 may act at stalled DNA replication forks and enhance Okazaki fragment maturation. Like its eukaryotic homologues, BsPif1 resolves R-loop structures and unwinds DNA–RNA hybrids. Furthermore, BsPif1 efficiently unfolds G-quadruplexes and disrupts nucleoprotein complexes. Altogether, these results highlight that prokaryotic Pif1 helicases may resolve common issues that arise during DNA transactions. Interestingly, we found that BsPif1 is different from yeast Pif1, but resembles more human Pif1 with regard to substrate specificity, helicase activity and mode of action. These findings are discussed in the context of the possible functions of prokaryotic Pif1 helicases in vivo. 相似文献
The mechanisms of persistence and virulence associated with Candida glabrata infections are poorly understood, limiting the ability to fight this fungal pathogen. In this study, the multidrug resistance transporters CgTpo1_1 and CgTpo1_2 are shown to play a role in C. glabrata virulence. The survival of the infection model Galleria mellonella, infected with C. glabrata, was found to increase upon the deletion of either CgTPO1_1 or CgTPO1_2. The underlying mechanisms were further explored. In the case of CgTpo1_1, this phenotype was found to be consistent with the observation that it confers resistance to antimicrobial peptides (AMP), such as the human AMP histatin‐5. The deletion of CgTPO1_2, on the other hand, was found to limit the survival of C. glabrata cells when exposed to phagocytosis and impair biofilm formation. Interestingly, CgTPO1_2 expression was found to be up‐regulated during biofilm formation, but and its deletion leads to a decreased expression of adhesin‐encoding genes during biofilm formation, which is consistent with a role in biofilm formation. CgTPO1_2 expression was further seen to decrease plasma membrane potential and affect ergosterol and fatty acid content. Altogether, CgTpo1_1 and CgTpo1_2 appear to play an important role in the virulence of C. glabrata infections, being at the cross‐road between multidrug resistance and pathogenesis. 相似文献
Circular RNAs (circRNAs) are a newly validated type of noncoding RNAs recently found to be deregulated in several human cancers. More accurate and specific noninvasive biomarkers are strongly needed for better diagnosis and prognosis of hepatocellular carcinoma (HCC). We performed a bioinformatics analysis to retrieve a novel panel of circRNAs potentially relevant to HCC. We examined their expression in the sera of 68 patients with HCC, 60 patients with chronic hepatitis C, and 36 healthy controls using quantitative polymerase chain reaction. We examined the performance characteristics of the selected circRNA biomarker panel in comparison with alpha-fetoprotein (AFP). In addition, we performed a survival analysis to correlate between their expression levels and patient survival. The circRNAs hsa_circ _00224 and hsa_circ _00520 showed a strong biomarker potential with relatively high sensitivities and specificities compared with AFP. The combined panel including the three circRNAs showed superior performance characteristics relative to those of AFP. The median follow-up period was 26 months. hsa_circ_00520 expression has been shown to be associated with relapse-free survival (P < 0.005). circRNAs hsa_circ_00156, hsa_circ_000224, and hsa_circ_000520 are novel potential biomarkers of high sensitivity and specificity, which could potentially be used in the diagnosis of HCC. 相似文献
Vitamin C is one of the most abundant exogenous antioxidants in the cell, and it is of the utmost importance to elucidate its mechanism of action against radicals. In this study, the reactivity of vitamin C toward OH and \( {HO}_2/{O}_2^{-} \) radicals in aqueous medium was analyzed by ab initio molecular dynamics using CPMD code. The simulations led to results similar to those of static studies or experiments for the pair of \( {HO}_2/{O}_2^{-} \) radicals but bring new insights for the reactivity with hydroxyl radical: the reaction takes place before the formation of an adduct and consists of two steps: first an electron is transferred to hydroxyl radical and then the ascorbyl radical loses a proton.
The Plasmodium falciparum parasite's ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis of these adaptations is critical to intervening successfully against malaria. To that end, we created a high-density genotyping array that assays over 17,000 single nucleotide polymorphisms (~ 1 SNP/kb), and applied it to 57 culture-adapted parasites from three continents. We characterized genome-wide genetic diversity within and between populations and identified numerous loci with signals of natural selection, suggesting their role in recent adaptation. In addition, we performed a genome-wide association study (GWAS), searching for loci correlated with resistance to thirteen antimalarials; we detected both known and novel resistance loci, including a new halofantrine resistance locus, PF10_0355. Through functional testing we demonstrated that PF10_0355 overexpression decreases sensitivity to halofantrine, mefloquine, and lumefantrine, but not to structurally unrelated antimalarials, and that increased gene copy number mediates resistance. Our GWAS and follow-on functional validation demonstrate the potential of genome-wide studies to elucidate functionally important loci in the malaria parasite genome. 相似文献
A novel HIV-1 recombinant clade (CRF51_01B) was recently identified among men who have sex with men (MSM) in Singapore. As cases of sexually transmitted HIV-1 infection increase concurrently in two socioeconomically intimate countries such as Malaysia and Singapore, cross transmission of HIV-1 between said countries is highly probable. In order to investigate the timeline for the emergence of HIV-1 CRF51_01B in Singapore and its possible introduction into Malaysia, 595 HIV-positive subjects recruited in Kuala Lumpur from 2008 to 2012 were screened. Phylogenetic relationship of 485 amplified polymerase gene sequences was determined through neighbour-joining method. Next, near-full length sequences were amplified for genomic sequences inferred to be CRF51_01B and subjected to further analysis implemented through Bayesian Markov chain Monte Carlo (MCMC) sampling and maximum likelihood methods. Based on the near full length genomes, two isolates formed a phylogenetic cluster with CRF51_01B sequences of Singapore origin, sharing identical recombination structure. Spatial and temporal information from Bayesian MCMC coalescent and maximum likelihood analysis of the protease, gp120 and gp41 genes suggest that Singapore is probably the country of origin of CRF51_01B (as early as in the mid-1990s) and featured a Malaysian who acquired the infection through heterosexual contact as host for its ancestral lineages. CRF51_01B then spread rapidly among the MSM in Singapore and Malaysia. Although the importation of CRF51_01B from Singapore to Malaysia is supported by coalescence analysis, the narrow timeframe of the transmission event indicates a closely linked epidemic. Discrepancies in the estimated divergence times suggest that CRF51_01B may have arisen through multiple recombination events from more than one parental lineage. We report the cross transmission of a novel CRF51_01B lineage between countries that involved different sexual risk groups. Understanding the cross-border transmission of HIV-1 involving sexual networks is crucial for effective intervention strategies in the region. 相似文献
Virologica Sinica - Laos is the only landlocked country in Southeast Asia and borders Thailand, Myanmar and Cambodia, the three countries in this region that have been hardest hit by human... 相似文献
The chromosomal location of the human VpreB gene was determined by Southern blotting analysis of restriction enzyme-digested DNAs from a panel of 17 mouse-human somatic cell hybrids. The pattern of hybridization of a VpreB-specific probe in conjunction with earlier analysis of several marker genes allowed the following conclusions: 1) VpreB is on human chromosome 22 within band 22q11.2 distal to the bcr-like gene, bcr-2 and proximal to the bcr-like gene, bcr-4. 2) VpreB has been localized relative to several constitutional and tumor-specific breakpoints within 22q 11.2, segregates in hybrids retaining 22q–chromosomes with some but not with all members of the
subgroup of the Vgenes, and is amplified with these genes in K562 cells. 3) The order of the loci on chromosome 22 is centromerebcr-2, VpreB,
. 相似文献