排序方式: 共有37条查询结果,搜索用时 171 毫秒
1.
Claudia Gaspar Iscia Lopes-Cendes Anita L. DeStefano Patrícia Maciel Isabel Silveira Paula Coutinho Patrick MacLeod Jorge Sequeiros Lindsay A. Farrer G. A. Rouleau 《Human genetics》1996,98(5):620-624
Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration originally described in families of Portuguese-Azorean
ancestry. The hypothesis that its present world distribution could result from the spread of an original founder mutation
has been raised. To test this possibility we have conducted a linkage disequilibrium study of markers segregating with the
MJD1 locus in a total of 64 unrelated families of different geographical origins. Significant association was detected between
the MJD1 locus and marker alleles at loci D14S280, D14S1050 and D14S81. All affected individuals, except one Chinese family, had allele
3 (237 bp) at D14S280. This finding is consistent with a founder effect in our MJD population. However, distinct haplotypes
were observed in patients originating from the two Azorean islands showing the highest disease prevalence; therefore, the
possible existence of more than one founder mutation can not be excluded with the markers currently available.
Received: 27 February 1996 / Revised: 4 June 1996 相似文献
2.
A Familial Factor Independent of CAG Repeat Length Influences Age at Onset of Machado-Joseph Disease 总被引:3,自引:0,他引:3 下载免费PDF全文
Anita L. DeStefano L. Adrienne Cupples Patricia Maciel Claudia Gaspar Joao Radvany David M. Dawson Lewis Sudarsky Lee Corwin Paula Coutinho Patrick MacLeod Jorge Sequeiros Guy A. Rouleau Lindsay A. Farrer 《American journal of human genetics》1996,59(1):119-127
Machado-Joseph disease (MJD) is a late-onset, progressive, neurodegenerative disorder caused by the expansion of an unstable trinucleotide (CAG) repeat sequence in a novel gene (MJD1) on chromosome 14. Previous studies showed that age at onset is negatively correlated with the number of CAG repeat units, but only part of the variation in onset age is explained by CAG repeat length. Ages at onset and CAG repeat lengths of 136 MJD patients from 23 kindreds of Portuguese descent were analyzed, to determine whether familial factors independent of CAG repeat length modulate age at onset of MJD. Correlation among sibs for onset age adjusted for CAG repeat length was .43, which indicates that an environmental or genetic factor common to sibs influences onset age. Positive correlations were also observed for avuncular (r = .22) and first-cousin pairs (r = .28), which supports the hypothesis that a genetic factor is influencing age at onset. Commingling analysis of onset ages adjusted for CAG repeat length identified three distributions in this population of affected individuals. Further studies of a much larger sample are needed to determine whether these distributions represent the influence of a genetic or environmental factor. 相似文献
3.
4.
Jose Bras Isabel Alonso Clara Barbot Maria?Manuela Costa Lee Darwent Tatiana Orme Jorge Sequeiros John Hardy Paula Coutinho Rita Guerreiro 《American journal of human genetics》2015,96(3):474-479
Hereditary autosomal-recessive cerebellar ataxias are a genetically and clinically heterogeneous group of disorders. We used homozygosity mapping and exome sequencing to study a cohort of nine Portuguese families who were identified during a nationwide, population-based, systematic survey as displaying a consistent phenotype of recessive ataxia with oculomotor apraxia (AOA). The integration of data from these analyses led to the identification of the same homozygous PNKP (polynucleotide kinase 3′-phosphatase) mutation, c.1123G>T (p.Gly375Trp), in three of the studied families. When analyzing this particular gene in the exome sequencing data from the remaining cohort, we identified homozygous or compound-heterozygous mutations in five other families. PNKP is a dual-function enzyme with a key role in different pathways of DNA-damage repair. Mutations in this gene have previously been associated with an autosomal-recessive syndrome characterized by microcephaly; early-onset, intractable seizures; and developmental delay (MCSZ). The finding of PNKP mutations associated with recessive AOA extends the phenotype associated with this gene and identifies a fourth locus that causes AOA. These data confirm that MCSZ and some forms of ataxia share etiological features, most likely reflecting the role of PNKP in DNA-repair mechanisms. 相似文献
5.
An early systemic response induced by magnetic resonance imaging (MRI)-guided interstitial percutaneous laser thermoablation was analyzed in 13 consecutive patients with malignant liver tumors by serum interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, its receptor TNFRI, and C-reactive protein (CRP) levels up to 72h after the procedures. Only IL-6 (p=0.033) and TNFRI (p<0.001) increased statistically significantly after ablation, while the TNF-alpha, IL-1 beta, and IL-10 levels remained unchanged. The peak median CRP response was 92mg/l. There was a dose-dependent correlation between the energy used and the maximum CRP values (tau=0.68, p=0.013). MRI-guided laser thermoablation induced an early systemic inflammatory reaction with statistically significantly elevated IL-6, TNFRI, and CRP levels but not TNF-alpha or IL-10 levels and without procedure-related complications, favoring this procedure as a safe therapeutic alternative for well-selected patients with liver tumors. 相似文献
6.
JH Lee JM Lee EM Ramos T Gillis JS Mysore S Kishikawa T Hadzi AE Hendricks MR Hayden PJ Morrison M Nance CA Ross RL Margolis F Squitieri C Gellera E Gomez-Tortosa C Ayuso O Suchowersky RJ Trent E McCusker A Novelletto M Frontali R Jones T Ashizawa S Frank MH Saint-Hilaire SM Hersch HD Rosas D Lucente MB Harrison A Zanko RK Abramson K Marder J Sequeiros G Bernhard Landwehrmeyer;On behalf of the Registry Study of the European Huntington’s Disease Network 《Biochemical and biophysical research communications》2012,426(3):404-408
7.
8.
Teresa Almeida Isabel Alonso Sandra Martins Eliana Marisa Ramos Luísa Azevedo Kinji Ohno António Amorim Maria Luiza Saraiva-Pereira Laura Bannach Jardim Tohru Matsuura Jorge Sequeiros Isabel Silveira 《PloS one》2009,4(2)
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia and seizures. The disease is caused by a large ATTCT repeat expansion in the ATXN10 gene. The first families reported with SCA10 were of Mexican origin, but the disease was soon after described in Brazilian families of mixed Portuguese and Amerindian ancestry. The origin of the SCA10 expansion and a possible founder effect that would account for its geographical distribution have been the source of speculation over the last years. To unravel the mutational origin and spread of the SCA10 expansion, we performed an extensive haplotype study, using closely linked STR markers and intragenic SNPs, in families from Brazil and Mexico. Our results showed (1) a shared disease haplotype for all Brazilian and one of the Mexican families, and (2) closely-related haplotypes for the additional SCA10 Mexican families; (3) little or null genetic distance in small normal alleles of different repeat sizes, from the same SNP lineage, indicating that they are being originated by a single step mechanism; and (4) a shared haplotype for pure and interrupted expanded alleles, pointing to a gene conversion model for its generation. In conclusion, we show evidence for an ancestral common origin for SCA10 in Latin America, which might have arisen in an ancestral Amerindian population and later have been spread into the mixed populations of Mexico and Brazil. 相似文献
9.
Correlation between CAG Repeat Length and Clinical Features in Machado-Joseph Disease 总被引:19,自引:3,他引:16 下载免费PDF全文
Patrícia Maciel Claudia Gaspar Anita L. DeStefano Isabel Silveira Paula Coutinho Joo Radvany David M. Dawson Lewis Sudarsky Joo Guimares Jose E. L. Loureiro Marjan M. Nezarati Lee I. Corwin Iscia Lopes-Cendes Karen Rooke Roger Rosenberg Patrick MacLeod Lindsay A. Farrer Jorge Sequeiros Guy A. Rouleau 《American journal of human genetics》1995,57(1):54-61
Machado-Joseph disease (MJD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene on 14q32.1. We confirmed the presence of this expansion in 156 MJD patients from 33 families of different geographic origins: 15 Portuguese Azorean, 2 Brazilian, and 16 North American of Portuguese Azorean descent. Normal chromosomes contain between 12 and 37 CAG repeats in the MJD gene, whereas MJD gene carriers have alleles within the expanded range of 62–84 CAG units. The distribution of expanded alleles and the gap between normal and expanded allele sizes is either inconsistent with a premutation hypothesis or most (if not all) of the alleles we studied descend from a common ancestor. There is a strong correlation between the expanded repeat size and the age at onset of the disease as well as the clinical presentation. There is mild instability of the CAG tract length with transmission of the expanded alleles; both increase and decrease in size between parents and progeny occur, with larger variations in male than in female transmissions. Together, these effects can partly explain the variability of age at onset and of phenotypic features in MJD; however, other modifying factors must exist. 相似文献
10.
Cynthia Sequeiros Marisol Vallejo Emilio Rogelio Marguet Nelda Lila Olivera 《Archives of microbiology》2010,192(4):237-245
After enrichment of Odontesthes platensis intestinal contents, 53 lactic acid bacteria (LAB) were isolated. From the four isolates that showed inhibitory activity
against Lactococcus garvieae 03/8460, strain TW34 was selected because it exerted the strongest inhibition. It also inhibited other Gram-positive bacteria,
but not Gram-negative fish pathogens. Phenotypic and 16S rDNA phylogenetic analyses showed that TW34 belongs to Lactococcus lactis. In addition, TW34 showed to be sensitive to different antibiotics. The production of the inhibitory agent against L. garvieae was growth associated, and it was significantly influenced by the incubation temperature. The optimal temperature for the
antimicrobial production was as low as 15°C. Both acidification and hydrogen peroxide production were ruled out as the source
of inhibition. In contrast, the antimicrobial activity was completely lost by treatment with proteolytic enzymes, which confirmed
that the inhibitory substance was a bacteriocin. The bacteriocin was highly thermostable (121°C for 15 min) and active between
pH 3 and 11. It remained stable for up to 2 months when stored at 4°C and up to 6 months at −20°C. Our results suggest that
the strain L. lactis TW34 could provide an alternative for lactococcosis control and therefore be considered for future challenge experiments
with fish. 相似文献