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1.
Iida A Saito S Sekine A Kitamura Y Kondo K Mishima C Osawa S Harigae S Nakamura Y 《Journal of human genetics》2001,46(9):522-528
Highly dense catalogs of human genetic variations, in combination with high-throughput genotyping technologies, are expected
to clarify individual genetic differences in pharmacological responsiveness and predispositions to common diseases. Here we
report single-nucleotide polymorphisms (SNPs) present among 48 Japanese individuals at the locus for the human ATP-binding
cassette transporter A1 (ABCA1) gene. ABCA1 plays a key role in apolipoprotein-mediated cholesterol transport, and mutations in this gene are responsible
for Tangier disease and familial high-density lipoprotein deficiency associated with reduced cholesterol efflux. We identified
a total of 162 SNPs, 149 of which were novel, within the 150-kb region encompassing the entire ABCA1 gene. Eight of the SNPs lie within coding elements, two in 5′ flanking regions, 147 in introns, and five in 3′ untranslated
regions, but none were found in 5′ untranslated or 3′ flanking regions. The ratio of transitions to transversions was approximately
2.37 to 1. Our dense SNP map of this region could serve as a powerful resource for studies of complex genetic diseases that
may be associated with ABCA1 and of individual responses to drug therapy.
Received: May 22, 2001 / Accepted: June 12, 2001 相似文献
2.
Staphylococcus aureus is an important human pathogen that is responsible for the vast majority of bacterial skin and soft tissue infections in
humans. S. aureus can also become more invasive and cause life-threatening infections such as bacteremia, pneumonia, abscesses of various organs,
meningitis, osteomyelitis, endocarditis, and sepsis. These infections represent a major public health threat due to the enormous
numbers of these infections and the widespread emergence of methicillin-resistant S. aureus (MRSA) strains. MSRA is endemic in hospitals worldwide and is rapidly spreading throughout the normal human population in
the community. The increasing frequency of MRSA infections has complicated treatment as these strains are more virulent and
are increasingly becoming resistant to multiple different classes of antibiotics. The important role of the immune response
against S. aureus infections cannot be overemphasized as humans with certain genetic and acquired immunodeficiency disorders are at an increased
risk for infection. Understanding the cutaneous immune responses against S. aureus is essential as most of these infections occur or originate from a site of infection or colonization of the skin and mucosa.
This review will summarize the innate immune responses against S. aureus skin infections, including antimicrobial peptides that have direct antimicrobial activity against S. aureus as well as pattern recognition receptors and proinflammatory cytokines that promote neutrophil abscess formation in the skin,
which is required for bacterial clearance. Finally, we will discuss the recent discoveries involving IL-17-mediated responses,
which provide a key link between cutaneous innate and adaptive immune responses against S. aureus skin infections. 相似文献
3.
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder of late onset, caused by the expansion of
a (CAG)n tract in the MJD1 gene. Using BLAST2 sequences between known cDNA variants transcribed by the MJD1 gene and a clone of human genomic DNA, six possible unknown intragenic single-nucleotide polymorphisms (SNPs), at variable
positions in the MJD1 gene, were identified. To confirm this, we studied a Portuguese control population, using polymerase chain reaction amplification
and single-strand conformation polymorphism analysis for each potential SNP. For four of the possible polymorphisms there
was no variability in our population, but the existence of three novel polymorphisms was confirmed: GTT_527/GTC_527, C_1178/A_1178, and A_1294/G_1294. The polymorphism GTT_527/GTC_527 (Val/ Val) is located in the coding region, whereas C_1178/A_1178 and A_1294/G_1294 are located in the 3′noncoding region of cDNA variants of the MJD1 gene, MJD2-1 and MJD1-1, respectively. All these novel SNPs are in Hardy-Weinberg equilibrium. These intragenic polymorphisms
can be useful for (1) the study of the origin of the MJD mutation(s), (2) the study of recombination events, (3) distinction
of chromosomes with alleles of identical (CAG)n size in genetic tests (homoallelism), (4) the study of genetic modifiers in the region flanking the MJD1 gene, and (5) association studies in other diseases.
Received: December 19, 2001 / Accepted: January 28, 2002 相似文献
4.
Distribution and genetic diversity of tomato-infecting begomoviruses in Brazil<Superscript>*</Superscript> 总被引:3,自引:0,他引:3
Ribeiro SG Ambrozevícius LP Avila AC Bezerra IC Calegario RF Fernandes JJ Lima MF de Mello RN Rocha H Zerbini FM 《Archives of virology》2003,148(2):281-295
Summary. Tomato-infecting begomoviruses have been reported throughout Brazil since the introduction of the B biotype of Bemisia tabaci. Here, we report a large scale survey on the distribution and genetic diversity of tomato-infecting begomoviruses. Tomato
samples with typical begomovirus symptoms were collected in seven different states, comprising the major tomato growing areas
of the country. Viruses were detected by polymerase chain reaction (PCR) using universal primers for the genus Begomovirus. PCR-amplified fragments were cloned and sequenced. Based on sequence comparisons and phylogenetic analyses, at least seven
previously undescribed species of begomoviruses were found. Four of the new viruses were found exclusively in the Southeastern
states, two exclusively in the Northeastern states, and one was found in both regions. Sequence comparisons reveal strong
evidence of recombination among the Brazilian begomoviruses. Together, the results indicate the existence of a high degree
of pre-existing genetic diversity among tomato-infecting begomoviruses in Brazil and suggest that these viruses have emerged
after being transferred from natural hosts to tomatoes, due to the introduction into Brazil of a novel polyfagous biotype
of the whitefly vector.
Received December 21, 2001; accepted September 1, 2002 相似文献
5.
Summary. The Odocoileus hemionus deer adenovirus (OdAdV-1) causes systemic and local vasculitis and proves extremely lethal for mule deer. To characterize
the virus, part of the genome flanking the fiber gene was cloned and sequenced. The sequence revealed two open-reading frames
that mapped to pVIII hexon-associated protein precursor and fiber protein of several other adenoviruses. The highest amino
acid homology for pVIII and fiber was found with the members of the proposed Atadenovirus genus: ovine adenovirus isolate 287 (OAdV-287), bovine adenovirus 4 (BAdV-4) and duck adenovirus 1 (DAdV-1). The homology
with bovine adenovirus type 3 (BAdV-3) proved low. The E3 region was not found between the gene for pVIII and fiber. These
data suggest that OdAdV-1 is a member of the Atadenovirus genus.
Received March 16, 2001 Accepted November 22, 2001 相似文献
6.
Park BL Kim LH Cheong HS Cho HY Kim EM Shin HD Kim YS Lee C 《Journal of human genetics》2004,49(8):449-454
CCND1 is an important cell-cycle regulatory protein associated with cell proliferation, poor prognosis and recurrence in cancer, while BCL2 is an important anti-apoptotic protein that plays a vital role in the regulation of the life span by controlling the rate of apoptosis. Recent studies have shown that CCND1 and BCL2 may be responsible for the body mass and the regulation of various metabolic processes. In an effort to discover additional polymorphism(s), we scrutinized the genetic polymorphisms in the CCND1 and BCL2. By direct DNA sequencing in 24 individuals, we identified 22 sequence variants within the 16 kb of whole CCND1 gene: one in exon 4, 17 in introns and four in the 3 UTR region. We also found eight sequence variants within 7.5 kb exon–intron boundaries of BCL2 gene: one in promoter, three in exon 1, and four in the 3 UTR region. Haplotypes, their frequencies and linkage disequilibrium coefficients (|D| and r
2), among polymorphisms were estimated. Among identified variants, seven and six variants of CCND1 and BCL2 were genotyped in a larger series of subjects (n=320). Statistical analyses of CCND1 and BCL2 polymorphisms with two metabolic phenotypes revealed no significant association. The information concerning genetic polymorphisms of CCND1 and BCL2 might provide valuable information for future genetic studies of diseases. 相似文献
7.
8.
Korsunenko A Chrisanfova G Lopatkin A Beer SA Voronin M Ryskov AP Semyenova SK 《Parasitology research》2012,110(2):833-841
Avian schistosome Trichobilharzia szidati is a member of the largest genus within the family Schistosomatidae (Trematoda). Population genetic structure of Trichobilharzia spp. schistosomes, causative agents of cercarial dermatitis in humans, has not been studied yet. The knowledge of the genetic
structure of trichobilharzian populations is essential for understanding the host–parasite coevolutionary dynamics and epidemiology
strategies. Here we examined genetic diversity in three geographically isolated local populations of T. szidati cercariae inhabiting Russia based on nuclear (randomly amplified polymorphic DNA, RAPD) and mt (cox1) markers. We analyzed T. szidati cercariae shed from seven naturally infected snails of Lymnaea stagnalis. Using three random primers, we demonstrated genetic variation among populations, thus posing genetic structure across geographic
sites. Moreover, T. szidati cercariae have been genetically structured among hosts (infrapopulations). Molecular variance analysis was performed to test
the significance of genetic differentiation within and between local populations. Of total parasitic diversity, 18.8% was
partitioned between populations, whereas the higher contribution (48.9%) corresponds to the differences among individual cercariae
within infrapopulations. In contrast to RAPD markers, a 1,125-bp fragment of cox1 mt gene failed to provide any significant within-species structure. The lack of geographic structuring was detected using
unique haplotypes which were determined in the current work for Moscow and Western Siberian local populations as well as obtained
previously for European isolates (Czech Republic and Germany). All T. szidati/Trichobilharzia ocellata haplotypes were found to be mixed across their geographical origin. 相似文献
9.
Iida A Saito S Sekine A Mishima C Kitamura Y Kondo K Harigae S Osawa S Nakamura Y 《Journal of human genetics》2002,47(1):14-19
Individual phenotypes with respect to drug response or toxicity often result from genetic variations that alter drug metabolism.
We have been focusing on genomic loci that encode various enzymes and transporters involved in the metabolism of drugs, and
have described more than 1200 single-nucleotide polymorphisms (SNPs) and other variations. Regarding the carbohydrate sulfotransferase
(CHST) gene family, we have already constructed high-density SNP maps of three genomic segments that included CHST2, CHST4, and CHST5, providing a total of 28 SNPs for those loci. In the present study, we screened DNA from 48 healthy Japanese volunteers for
SNPs at the CHST1 and CHST3 gene loci, by means of direct sequencing combined with a polymerase chain reaction method for amplifying genomic DNA, and
characterized 77 SNPs and four insertion–deletion polymorphisms. The collection of human variations presented here adds to
the archive of tools now available for investigating complex genetic diseases, population migration patterns, and a variety
of pharmacogenetic possibilities.
Received: September 18, 2001 / Accepted: October 28, 2001 相似文献
10.
Sevjidmaa Baasanjav Aleksander Jamsheer Mateusz Kolanczyk Denise Horn Tomasz Latos Katrin Hoffmann Anna Latos-Bielenska Stefan Mundlos 《BMC medical genetics》2010,11(1):110
Background
Osteopoikilosis is a rare autosomal dominant genetic disorder, characterised by the occurrence of the hyperostotic spots preferentially localized in the epiphyses and metaphyses of the long bones, and in the carpal and tarsal bones [1]. Heterozygous LEMD3 gene mutations were shown to be the primary cause of the disease [2]. Association of the primarily asymptomatic osteopokilosis with connective tissue nevi of the skin is categorized as Buschke-Ollendorff syndrome (BOS) [3]. Additionally, osteopoikilosis can coincide with melorheostosis (MRO), a more severe bone disease characterised by the ectopic bone formation on the periosteal and endosteal surface of the long bones [4–6]. However, not all MRO affected individuals carry germ-line LEMD3 mutations [7]. Thus, the genetic cause of MRO remains unknown. Here we describe a familial case of osteopoikilosis in which a novel heterozygous LEMD3 mutation coincides with a novel mutation in EXT1, a gene involved in aetiology of multiple exostosis syndrome. The patients affected with both LEMD3 and EXT1 gene mutations displayed typical features of the osteopoikilosis. There were no additional skeletal manifestations detected however, various non-skeletal pathologies coincided in this group. 相似文献11.
H. Ohmori Y. Makita M. Funamizu S. Chiba K. Ohtani Y. Suzuki N. Wakamiya A. Hata 《Journal of human genetics》2003,48(2):0082-0085
Collectins are a family of C-type lectins found in vertebrates. These proteins have four regions, a relatively short N-terminal
region, a collagen-like region, an alpha-helical coiled coil, and a carbohydrate recognition domain. Collectins are involved
in host defense through their ability to bind carbohydrate antigens on microorganisms. Type A scavenger receptors are classical-type
scavenger receptors that also have collagen-like domains. We previously described a new scavenger receptor, collectin from
placenta [collectin placenta 1 (CL-P1)]. CL-P1 is a type II membrane protein with all four regions. We found that CL-P1 can
bind and phagocytize both bacteria and yeast. In addition to that, it reacts with oxidized low-density lipoprotein (LDL) but
not with acetylated LDL. These results suggest that CL-P1 might play important roles in host defenses and/or atherosclerosis
formation. One rational strategy to study the role of CL-P1 in these pathological conditions would be to perform a haplotype
association study using human samples. As a first step for this strategy, we analyzed the haplotype structure of the CL-P1 gene. By sequencing the CL-P1 gene in ten Japanese volunteers, we identified five single-nucleotide polymorphisms (SNPs) with a minor allele frequency
of at least 29%. To obtain SNPs in the 5′-upstream region of the gene, we screened a total of 20 SNPs described in the database
and finally picked up one SNP for the present study. Thus, a total of six SNPs, one in the 5′-upstream region, two in intron
2, one in exon 5, and two in exon 6, were used to analyze the haplotype structure of the gene, with DNAs derived from 54 individuals
(108 alleles). The analysis revealed that only two of six SNPs showed significant linkage disequilibrium (r
2 > 0.5) with each other. This haplotype information may be useful in disease-association studies in which a contribution of
the CL-P1 gene has been suspected, especially in immunological disturbance or atherosclerosis. Two SNPs in exon 6, both leading to
amino acid substitutions, could be candidates for influencing disease susceptibility.
Received: September 12, 2002 / Accepted: November 12, 2002
Present address Department of Public Health, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Tel. +81-43-226-2067; Fax +81-43-226-2070 e-mail: ahata@med.m.chiba-u.ac.jp
Acknowledgments We are grateful to Katsura Nakanishi and Ayako Sado for their technical assistance. This work was supported by Grant-in-Aid
for Scientific Research on Priority Areas (C) “Medical Genome Science” from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan.
Correspondence to:A. Hata 相似文献
12.
Duo1, a major component of the Dam1 complex which has been found in two species of yeast (the budding yeast Saccharomyces cerevisae and the fission yeast Schizosaccharomyces pombe), is involved in mitosis-related chromosome segregation, while its relevance to pathogenicity in filamentous fungi remains
unclear. This report elucidated this very fact in the case of the rice blast fungus Magnaporthe oryzae. A gene designated MoDUO1 that encodes a Duo1-like homolog (MoDuo1) was discovered in the M. oryzae genome. Two types of MoDUO1 mutants were obtained using genetic approaches of Agrobacterium-mediated gene disruption and homologous recombination. Both disruption and deletion of MoDUO1 can exert profound effects on the formation pattern of conidiophores and conidial morphology, such as abnormal nucleic numbers
in conidia and delayed extension of infectious hyphae. Intriguingly, plant infection assays demonstrated that inactivation
of MoDUO1 significantly attenuates the virulence in its natural host rice leaves, and functional complementation can restore it. Subcellular
localization assays showed that MoDuo1 is mainly distributed in the cytosol of fungal cells. Proteomics-based investigation
revealed that the expression of four mitosis-related proteins is shut down in the MoDUO1 mutant, suggesting that MoDuo1 may have a function in mitosis. In light of the fact that Duo1 orthologs are widespread in
plant and human fungal pathogens, our finding may represent a common mechanism underlying fungal virulence. To the best of
our knowledge, this is the first example of linking a Duo1-like homolog to the pathogenesis of a pathogenic fungus, which
might provide clues to additional studies on the role of Dam1 complex in M. oryzae and its interaction with rice. 相似文献
13.
Dermatophytes are the fungi that can cause infections of skin, hair, and nails due to their ability to utilize keratin. The
genetic transformation systems of dermatophytes were successfully applied to Trichophyton mentagrophytes and Microsporum canis. Here we describe the procedure for genetic transformation of Trichophyton rubrum by electroporation of their germinated conidia. A linearized transformation vector (pCHSH75-Pch/GFP/TtrpC) containing bacterial
hygromycin B phosphotransferase gene (hph) and green fluorescent protein gene (egfp) was introduced into the germinated conidia of T. rubrum by electroporation. PCR reaction analysis showed that egfp gene was integrated randomly and Southern blotting analysis demonstrated a single integration of hph gene into the chromosomal DNA of randomly selected transformant. In this work we report the efficient transformation and
selection of the stable T. rubrum transformants. 相似文献
14.
Amparo Tolosa Julio Sanjuán Adam M Dagnall María D Moltó Neus Herrero Rosa de Frutos 《BMC medical genetics》2010,11(1):114
Background
Schizophrenia is considered a language related human specific disease. Previous studies have reported evidence of positive selection for schizophrenia-associated genes specific to the human lineage. FOXP2 shows two important features as a convincing candidate gene for schizophrenia vulnerability: FOXP2 is the first gene related to a language disorder, and it has been subject to positive selection in the human lineage. 相似文献15.
Hassan Vahidnezhad Leila Youssefian Soheila Sotoudeh Lu Liu Alyson Guy Patricia A. Lovell Ariana Kariminejad Sirous Zeinali John A. McGrath Jouni Uitto 《Human mutation》2020,41(5):906-912
Next‐generation sequencing (NGS) is helpful in diagnosing complex genetic disorders and phenotypes, particularly when more than one overlapping condition is present. From a large cohort of 362 families with clinical manifestations of skin and mucosal fragility, referred by several major medical centers, one patient was found by NGS to have two overlapping heritable skin diseases, recessive dystrophic epidermolysis bullosa (RDEB; COL7A1 mutations) and acrodermatitis enteropathica (AE; SLC39A4 mutations). The pathogenicity of the variants was studied at gene expression as well as ultrastructural and tissue levels. Although there is no specific treatment for RDEB except avoiding trauma, supplementation with oral zinc (3 mg·kg?1·day?1) for the AE resulted in rapid amelioration of the skin findings. This case demonstrates the power of NGS in identifying two genetically unlinked diseases that led to effective treatment with major clinical benefits as an example of genomics‐guided treatment. 相似文献
16.
17.
The yeast Pichia ciferrii produces large quantities of the sphingoid base tetraacetyl phytosphingosine (TAPS) and is an interesting platform organism
for the biotechnological production of sphingolipids and ceramides. Ceramides have attracted great attention as a specialty
ingredient for moisture retention and protection of the skin in the cosmetics industry. First attempts have been started to
metabolically engineer P. ciferrii for improved production of TAPS and other sphingoid bases. However, rational metabolic engineering of P. ciferrii is difficult due to a low gene targeting efficiency. In eukaryotes, two major pathways coexist, which are responsible for
genomic DNA integration, homologous recombination (HR) and non-homologous end joining (NHEJ). Integration via HR is targeted,
while NHEJ involves ectopic (non-targeted) integration depending on a ligation step mediated by DNA ligase IV (Lig4). Here,
we demonstrate a dramatical increase in gene targeting efficiency in a P. ciferrii
lig4 knockout strain, deficient in NHEJ. Furthermore, a quick and easy to use freeze–thaw method was developed to transform P. ciferrii with high efficiency. Owing to the ability of targeting genomic DNA integration our results pave the way for further genetic
and metabolic engineering approaches with P. ciferrii by means of knocking out or overexpressing predestinated genes. 相似文献
18.
G. Roversi A. Beghini G. Zambruno M. Paradisi L. Larizza 《Journal of human genetics》2003,48(2):0107-0109
Rothmund-Thomson syndrome is a rare autosomal recessive disorder characterized by a widely heterogeneous clinical presentation.
Only a subset of clinically diagnosed patients carry RECQL4 gene mutations, probably because of their genetic heterogeneity and/or the complexity of molecular testing. We here describe
the polymorphic sites of the RECQL4 gene that detail its genomic structure and may be of interest as modulators of the splicing process and gene expression.
We characterized two novel and one already described single-nucleotide polymorphism in the coding region of the RECQL4 gene, which were shown by the exonic splicing enhancer (ESE) score matrix to fall into high-score motifs recognized by serine/arginine-rich
proteins. We also describe the genomic structure of a G-C rich minisatellite flanking the 3′ splice site of IVS12 in the helicase
domain of the RECQL4 gene, which may enhance mutations such as those described at the IVS12 acceptor site. RECQL4 polymorphic sites may be useful for identifying alleles associated with missplicing and, more generally, in cancer-susceptibility
association studies.
Received: October 24, 2002 / Accepted: November 21, 2002
Acknowledgments This study was supported by the AIRC (Associazione Italiana per la Ricerca sul Cancro): 2001 grant to L.L.
Correspondence to:L. Larizza 相似文献
19.
In the fungus Fusarium sporotrichioides, biosynthesis of trichothecene mycotoxins requires at least three genetic loci: a core 12-gene cluster, a smaller two-gene cluster, and a single-gene locus. Here, we describe the Tri15 gene, which represents a fourth locus involved in trichothecene biosynthesis. Tri15 is predicted to encode a Cys2-His2 zinc finger protein and is expressed in a manner similar to genes in the core trichothecene gene cluster. However, disruption of F. sporotrichioides Tri15 does not affect production of T-2 toxin, the major trichothecene produced by this fungus. This result suggests that Tri15 is not necessary for the production of toxin. Cultures with exogenously added T-2 toxin have high levels of Tri15 expression and no detectable expression of the trichothecene biosynthetic genes Tri5 and Tri6. The expression analysis is consistent with Tri15 being a negative regulator of at least some of the trichothecene biosynthetic genes. In F. graminearum, Tri15 has been mapped to linkage group 2 and is therefore unlinked to the main trichothecene biosynthetic gene cluster.Communicated by U. Kück 相似文献
20.
Bert B.A. de Vries Bert H.J. Eussen Otto P. van Diggelen Annet van der Heide Wouter H. Deelen Lutgarde C.P. Govaerts Dick Lindhout Cokkie H. Wouters Jan O. Van Hemel 《American journal of medical genetics. Part A》1999,87(2):189-194
In a 3-year-old boy with short stature, developmental delay, and dry skin, steroid sulphatase deficiency and a submicroscopic terminal deletion of Xp were found. Except for the short stature, no major clinical signs of X-linked recessive chondrodysplasia punctata could be observed. His mother had lowered steroid sulphatase activity compatible with carriership for X-linked ichthyosis and a submicroscopic translocation (X;14)(p22.31;p11.1). This finding combined with a normal amplification of exons 1, 5, and 10 of the STS gene from propositus' DNA suggested a breakpoint upstream of the STS gene. The submicroscopic maternal translocation had important implications for genetic counseling. This case report illustrates that contiguous gene syndrome related to the Xpter region may have an atypical clinical presentation and the usefulness of combined clinical, biochemical, molecular, and fluorescence in situ hybridization analysis. Am. J. Med. Genet. 87:189–194, 1999. © 1999 Wiley-Liss, Inc. 相似文献