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[
{
"name": "systemic lupus erythematosus",
"pos": [
31,
59
],
"type": "Disease"
}
] | The proband , who has inactive systemic lupus erythematosus is completely lacking C5 , while her healthy half - sister has 1 - 2 % of normal levels . |
[] | Both sera were severely impaired in their ability to generate chemotactic activity for normal human neutrophils upon incubation with aggregated human gamma - globulin or Escherichia coli endotoxin . |
[] | This function was fully restored in the siblings serum , and substantially improved in the probands serum , by addition of highly purified human C5 to normal serum concentrations . |
[
{
"name": "C5 deficiency",
"pos": [
68,
81
],
"type": "Disease"
}
] | Sera from eight family members who were apparently heterozygous for C5 deficiency gave normal chemotactic scores . |
[
{
"name": "C5D",
"pos": [
15,
18
],
"type": "Disease"
}
] | The ability of C5D serum to opsonize Saccharomyces cerevisiae ( bakers yeast ) or Candida albicans for ingestion by normal neutrophils was completely normal . |
[
{
"name": "C5D",
"pos": [
14,
17
],
"type": "Disease"
}
] | In addition , C5D serum was capable of promoting normal phagocytosis and intracellular killing of Staphylococcus aureus . |
[
{
"name": "paroxysmal nocturnal hemoglobinuria",
"pos": [
88,
123
],
"type": "Disease"
}
] | The probands serum was incapable of mediating lysis of erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria in both the sucrose hemolysia and acid hemolysis tests , and also lacked bactericidal activity against sensitized or unsensitized Salmonella typhi . |
[] | The siblings serum , containing only 1 - 2 % of normal C5 , effectively lysed S . typhi , but only at eightfold lower serum dilutions as compared to normals . |
[] | These findings underscore the critical role of C5 in the generation of chemotactic activity and in cytolytic reactions , as opposed to a nonobligatory or minimal role in opsonization , at least for the organisms under study . . |
[
{
"name": "peroxisomal disorders",
"pos": [
118,
139
],
"type": "Disease"
}
] | Human peroxisomal targeting signal - 1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders . |
[] | Two peroxisomal targeting signals , PTS1 and PTS2 , are involved in the import of proteins into the peroxisome matrix . |
[
{
"name": "peroxisomal deficiency disorders",
"pos": [
38,
70
],
"type": "Disease"
}
] | Human patients with fatal generalized peroxisomal deficiency disorders fall into at least nine genetic complementation groups . |
[] | Cells from many of these patients are deficient in the import of PTS1 - containing proteins , but the causes of the protein - import defect in these patients are unknown . |
[] | We have cloned and sequenced the human cDNA homologue ( PTS1R ) of the Pichia pastoris PAS8 gene , the PTS1 receptor ( McCollum , D . , E . Monosov , and S . Subramani . 1993 . J . Cell Biol . 121 761 - 774 ) . |
[] | The PTS1R mRNA is expressed in all human tissues examined . |
[] | Antibodies to the human PTS1R recognize this protein in human , monkey , rat , and hamster cells . |
[] | The protein is localized mainly in the cytosol but is also found to be associated with peroxisomes . |
[] | Part of the peroxisomal PTS1R protein is tightly bound to the peroxisomal membrane . |
[] | Antibodies to PTS1R inhibit peroxisomal protein - import of PTS1 - containing proteins in a permeabilized CHO cell system . |
[] | In vitro - translated PTS1R protein specifically binds a serine - lysine - leucine - peptide . |
[] | A PAS8 - PTS1R fusion protein complements the P . pastoris pas8 mutant . |
[
{
"name": "PTS1 protein - import defect",
"pos": [
36,
64
],
"type": "Disease"
},
{
"name": "neonatal adrenoleukodystrophy",
"pos": [
166,
195
],
"type": "Disease"
},
{
"name": "Zellweger syndrome",
"pos": [
199,
217
],
"type": "Disease"
}
] | The PTS1R cDNA also complements the PTS1 protein - import defect in skin fibroblasts from patients - - belonging to complementation group two - - diagnosed as having neonatal adrenoleukodystrophy or Zellweger syndrome . |
[
{
"name": "peroxisomal disorder",
"pos": [
75,
95
],
"type": "Disease"
}
] | The PTS1R gene has been localized to a chromosomal location where no other peroxisomal disorder genes are known to map . |
[
{
"name": "protein - import deficiency",
"pos": [
73,
100
],
"type": "Disease"
},
{
"name": "peroxisomal disorders",
"pos": [
110,
131
],
"type": "Disease"
}
] | Our findings represent the only case in which the molecular basis of the protein - import deficiency in human peroxisomal disorders is understood . |
[
{
"name": "hereditary and non hereditary retinoblastoma",
"pos": [
78,
122
],
"type": "Disease"
}
] | Spectrum of germline mutations in the RB1 gene : a study of 232 patients with hereditary and non hereditary retinoblastoma . |
[
{
"name": "retinoblastoma",
"pos": [
71,
85
],
"type": "Disease"
}
] | Germline mutations in the RB1 gene confer hereditary predisposition to retinoblastoma . |
[
{
"name": "hereditary or non hereditary retinoblastoma",
"pos": [
73,
116
],
"type": "Disease"
}
] | We have performed a mutation survey of the RB1 gene in 232 patients with hereditary or non hereditary retinoblastoma . |
[] | We systematically explored all 27 exons and flanking sequences as well as the promotor . |
[] | All types of point mutations are represented and are found unequally distributed along the RB1 gene sequence . |
[] | In the population we studied , exons 3 , 8 , 18 and 19 are preferentially altered . |
[] | The range of frequency of detection of germline mutations is about 20 % , indicating that other mechanisms of inactivation of RB1 should be involved . |
[
{
"name": "retinoblastoma",
"pos": [
91,
105
],
"type": "Disease"
}
] | The spectrum of mutations presented here should help to improve the clinical management of retinoblastoma and to understand the molecular mechanisms leading to tumorigenesis . . |
[
{
"name": "Aniridia",
"pos": [
0,
8
],
"type": "Disease"
}
] | Aniridia - associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype . |
[
{
"name": "aniridia",
"pos": [
31,
39
],
"type": "Disease"
},
{
"name": "absence of iris",
"pos": [
42,
57
],
"type": "Disease"
}
] | Current evidence suggests that aniridia ( absence of iris ) is caused by loss of function of one copy of the PAX6 gene , which maps to 11p13 . |
[
{
"name": "aniridia",
"pos": [
47,
55
],
"type": "Disease"
}
] | We present the further characterisation of two aniridia pedigrees in which the disease segregates with chromosomal rearrangements which involve 11p13 but do not disrupt the PAX6 gene . |
[] | We have isolated three human YAC clones which encompass the PAX6 locus and we have used these to show that in both cases the chromosomal breakpoint is at least 85 kb distal of the 3 end of PAX6 . |
[] | In addition , the open reading frame of PAX6 is apparently free of mutations . |
[] | We propose that the PAX6 gene on the rearranged chromosome 11 is in an inappropriate chromatin environment for normal expression and therefore that a position effect is the underlying mechanism of disease in these families . . |
[
{
"name": "sporadic ovarian tumours",
"pos": [
39,
63
],
"type": "Disease"
}
] | Somatic mutations in the BRCA1 gene in sporadic ovarian tumours . |
[
{
"name": "autosomal dominant syndrome",
"pos": [
57,
84
],
"type": "Disease"
},
{
"name": "breast and ovarian cancer",
"pos": [
116,
141
],
"type": "Disease"
},
{
"name": "tumours",
"pos": [
170,
177
],
"type": "Disease"
}
] | The BRCA1 gene on chromosome 17q21 is responsible for an autosomal dominant syndrome of increased susceptibility to breast and ovarian cancer but no somatic mutations in tumours have yet been described . |
[
{
"name": "tumour",
"pos": [
97,
103
],
"type": "Disease"
},
{
"name": "ovarian cancers",
"pos": [
131,
146
],
"type": "Disease"
}
] | To study the potential role of BRCA1 in sporadic carcinogenesis , we analysed the genomic DNA of tumour and normal fractions of 47 ovarian cancers for mutations in BRCA1 using the single - strand conformation polymorphism technique . |
[
{
"name": "tumours",
"pos": [
53,
60
],
"type": "Disease"
}
] | We now describe somatic mutations in the DNA of four tumours which also had loss of heterozygosity ( LOH ) at a BRCA1 intragenic marker . |
[
{
"name": "tumour",
"pos": [
19,
25
],
"type": "Disease"
},
{
"name": "ovarian cancers",
"pos": [
151,
166
],
"type": "Disease"
}
] | Our data support a tumour suppressor mechanism for BRCA1 ; somatic mutations and LOH may result in inactivation of BRCA1 in at least a small number of ovarian cancers . . |
[
{
"name": "sporadic breast cancer",
"pos": [
77,
99
],
"type": "Disease"
}
] | Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progression . |
[
{
"name": "familial breast and ovarian cancer",
"pos": [
40,
74
],
"type": "Disease"
},
{
"name": "non - hereditary ( sporadic ) breast cancer",
"pos": [
102,
145
],
"type": "Disease"
}
] | We have characterized expression of the familial breast and ovarian cancer gene , BRCA1 , in cases of non - hereditary ( sporadic ) breast cancer and analyzed the effect of antisense inhibition of BRCA1 on the proliferative rate of mammary epithelial cells . |
[
{
"name": "carcinoma in situ",
"pos": [
68,
85
],
"type": "Disease"
},
{
"name": "invasive cancer",
"pos": [
89,
104
],
"type": "Disease"
}
] | BRCA1 mRNA levels are markedly decreased during the transition from carcinoma in situ to invasive cancer . |
[] | Experimental inhibition of BRCA1 expression with antisense oligonucleotides produced accelerated growth of normal and malignant mammary cells , but had no effect on non - mammary epithelial cells . |
[
{
"name": "breast cancer",
"pos": [
143,
156
],
"type": "Disease"
}
] | These studies suggest that BRCA1 may normally serve as a negative regulator of mammary epithelial cell growth whose function is compromised in breast cancer either by direct mutation or alterations in gene expression . . |
[
{
"name": "Duchenne muscular dystrophy",
"pos": [
90,
117
],
"type": "Disease"
}
] | Additional case of female monozygotic twins discordant for the clinical manifestations of Duchenne muscular dystrophy due to opposite X - chromosome inactivation . |
[
{
"name": "DMD",
"pos": [
88,
91
],
"type": "Disease"
},
{
"name": "Duchenne muscular dystrophy",
"pos": [
147,
174
],
"type": "Disease"
}
] | A pair of female monozygotic ( MZ ) twins , heterozygous carriers for a deletion in the DMD gene and discordant for the clinical manifestations of Duchenne muscular dystrophy , were analyzed by molecular studies , in situ hybridization , and methylation pattern of X chromosomes to search for opposite X inactivation as an explanation of their clinical discordance . |
[] | Results in lymphocytes and skin fibroblast cell lines suggest a partial mirror inactivation with the normal X chromosome preferentially active in the unaffected twin , and the maternal deleted X chromosome preferentially active in the affected twin . |
[
{
"name": "X - linked diseases",
"pos": [
51,
70
],
"type": "Disease"
}
] | A review shows that MZ female twins discordant for X - linked diseases are not uncommon . |
[] | Twinning and X inactivation may be interrelated and could explain the female twins discordant for X - linked traits . . |
[
{
"name": "X - linked adrenoleukodystrophy",
"pos": [
0,
31
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
34,
37
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
66,
69
],
"type": "Disease"
}
] | X - linked adrenoleukodystrophy ( ALD ) : a novel mutation of the ALD gene in 6 members of a family presenting with 5 different phenotypes . |
[
{
"name": "adrenoleukodystrophy",
"pos": [
17,
37
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
40,
43
],
"type": "Disease"
},
{
"name": "adolescent ALD",
"pos": [
71,
85
],
"type": "Disease"
}
] | Fragments of the adrenoleukodystrophy ( ALD ) cDNA from a patient with adolescent ALD were amplified by polymerase chain reaction and subcloned . |
[
{
"name": "ALD",
"pos": [
46,
49
],
"type": "Disease"
}
] | Bidirectional sequencing of the entire coding ALD gene disclosed a cytosine to guanine transversion at nucleotide 1451 in exon five , resulting in substitution of proline 484 by arginine . |
[
{
"name": "cerebral ALD",
"pos": [
54,
66
],
"type": "Disease"
},
{
"name": "adrenomyeloneuropathy",
"pos": [
73,
94
],
"type": "Disease"
},
{
"name": "Addison only",
"pos": [
101,
113
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
287,
290
],
"type": "Disease"
}
] | Five of nine siblings of the patient , comprising two cerebral ALD , one adrenomyeloneuropathy , one Addison only as well as the symptomatic mother ( all accumulating very long chain fatty acids ) carried this mutation , which was not found in the unaffected persons , in five unrelated ALD patients , and in twenty controls . |
[] | We propose that this missense mutation generated the disease per se as well as the metabolic defect ; the different phenotypes , however , must have originated by means of additional pathogenetic factors . . |
[
{
"name": "Norrie disease",
"pos": [
46,
60
],
"type": "Disease"
}
] | Novel mutation at the initiation codon in the Norrie disease gene in two Japanese families . |
[
{
"name": "Norrie disease",
"pos": [
37,
51
],
"type": "Disease"
},
{
"name": "ND",
"pos": [
54,
56
],
"type": "Disease"
},
{
"name": "ND",
"pos": [
151,
153
],
"type": "Disease"
},
{
"name": "mental retardation",
"pos": [
161,
179
],
"type": "Disease"
},
{
"name": "hearing impairment",
"pos": [
183,
201
],
"type": "Disease"
}
] | We have identified a new mutation of Norrie disease ( ND ) gene in two Japanese males from unrelated families ; they showed typical ocular features of ND but no mental retardation or hearing impairment . |
[
{
"name": "ND",
"pos": [
79,
81
],
"type": "Disease"
}
] | A mutation was found in both patients at the initiation codon of exon 2 of the ND gene ( ATG to GTG ) , with otherwise normal nucleotide sequences . |
[] | Their mothers had the normal and mutant types of the gene , which was expected for heterozygotes of the disease . |
[
{
"name": "ND",
"pos": [
64,
66
],
"type": "Disease"
},
{
"name": "ND",
"pos": [
151,
153
],
"type": "Disease"
}
] | The mutation of the initiation codon would cause the failure of ND gene expression or a defect in translation thereby truncating the amino terminus of ND protein . |
[
{
"name": "ND",
"pos": [
67,
69
],
"type": "Disease"
}
] | In view of the rarity and marked heterogeneity of mutations in the ND gene , the present apparently unrelated Japanese families who have lived in the same area for over two centuries presumably share the origin of the mutation . . |
[
{
"name": "myotonic dystrophy",
"pos": [
45,
63
],
"type": "Disease"
}
] | Anticipation resulting in elimination of the myotonic dystrophy gene : a follow up study of one extended family . |
[
{
"name": "myotonic dystrophy",
"pos": [
34,
52
],
"type": "Disease"
},
{
"name": "DM",
"pos": [
55,
57
],
"type": "Disease"
},
{
"name": "DM",
"pos": [
159,
161
],
"type": "Disease"
}
] | We have re - examined an extended myotonic dystrophy ( DM ) family , previously described in 1955 , in order to study the long term effects of anticipation in DM and in particular the implications for families affected by this disease . |
[] | This follow up study provides data on 35 gene carriers and 46 asymptomatic at risk family members in five generations . |
[
{
"name": "congenital disease",
"pos": [
80,
98
],
"type": "Disease"
}
] | Clinical anticipation , defined as the cascade of mild , adult , childhood , or congenital disease in subsequent generations , appeared to be a relentless process , occurring in all affected branches of the family . |
[] | The cascade was found to proceed asynchronously in the different branches , mainly because of an unequal number of generations with mild disease . |
[] | The transition from the mild to the adult type was associated with transmission through a male parent . |
[] | Stable transmission of the asymptomatic / mild phenotype showed a female transmission bias . |
[] | We further examined the extent and causes of gene loss in this pedigree . |
[
{
"name": "infertility",
"pos": [
55,
66
],
"type": "Disease"
},
{
"name": "mentally retarded",
"pos": [
131,
148
],
"type": "Disease"
}
] | Gene loss in the patient group was complete , owing to infertility of the male patients with adult onset disease and the fact that mentally retarded patients did not procreate . |
[] | Out of the 46 at risk subjects in the two youngest generations , only one was found to have a full mutation . |
[] | This is the only subject who may transmit the gene to the sixth generation . |
[] | No protomutation carriers were found in the fourth and fifth generations . |
[
{
"name": "DM",
"pos": [
41,
43
],
"type": "Disease"
}
] | Therefore it is highly probable that the DM gene will be eliminated from this pedigree within one generation . |
[
{
"name": "DM",
"pos": [
33,
35
],
"type": "Disease"
}
] | The high population frequency of DM can at present not be explained by the contribution of asymptomatic cases in the younger generations of known families , but is probably caused by the events in the ancestral generations . . |
[
{
"name": "spinal cerebellar ataxia",
"pos": [
13,
37
],
"type": "Disease"
}
] | The gene for spinal cerebellar ataxia 3 ( SCA3 ) is located in a region of approximately 3 cM on chromosome 14q24 . 3 - q32 . 2 . |
[
{
"name": "spinal cerebellar ataxia",
"pos": [
20,
44
],
"type": "Disease"
}
] | SCA3 , the gene for spinal cerebellar ataxia 3 , was recently mapped to a 15 - cM interval between D14S67 and D14S81 on chromosome 14q , by linkage analysis in two families of French ancestry . |
[] | The SCA3 candidate region has now been refined by linkage analysis with four new microsatellite markers ( D14S256 , D14S291 , D14S280 , and AFM343vf1 ) in the same two families , in which 19 additional individuals were genotyped , and in a third French family . |
[] | Combined two - point linkage analyses show that the new markers , D14S280 and AFM343vf1 , are tightly linked to the SCA3 locus , with maximal lod scores , at recombination fraction , ( theta ) = . |
[] | 00 , of 7 . |
[] | 05 and 13 . |
[] | 70 , respectively . |
[] | Combined multipoint and recombinant haplotype analyses localize the SCA3 locus to a 3 - cM interval flanked by D14S291 and D14S81 . |
[] | The same allele for D14S280 segregates with the disease locus in the three kindreds . |
[] | This allele is frequent in the French population , however , and linkage disequilibrium is not clearly established . |
[] | The SCA3 locus remains within the 29 - cM region on 14q24 . |
[] | 3 - q32 . |
[
{
"name": "Machado - Joseph disease",
"pos": [
30,
54
],
"type": "Disease"
}
] | 2 containing the gene for the Machado - Joseph disease , which is clinically related to the phenotype determined by SCA3 , but it cannot yet be concluded that both diseases result from alterations of the same gene |
[
{
"name": "breast - ovarian cancer",
"pos": [
46,
69
],
"type": "Disease"
}
] | An evaluation of genetic heterogeneity in 145 breast - ovarian cancer families . |
[
{
"name": "Breast Cancer",
"pos": [
0,
13
],
"type": "Disease"
}
] | Breast Cancer Linkage Consortium . |
[
{
"name": "breast - ovary cancer - family syndrome",
"pos": [
4,
43
],
"type": "Disease"
},
{
"name": "cancer of the breast and ovaries",
"pos": [
76,
108
],
"type": "Disease"
}
] | The breast - ovary cancer - family syndrome is a dominant predisposition to cancer of the breast and ovaries which has been mapped to chromosome region 17q12 - q21 . |
[
{
"name": "breast - ovary cancer",
"pos": [
32,
53
],
"type": "Disease"
}
] | The majority , but not all , of breast - ovary cancer families show linkage to this susceptibility locus , designated BRCA1 . |
[
{
"name": "breast and ovarian cancer",
"pos": [
75,
100
],
"type": "Disease"
}
] | We report here the results of a linkage analysis of 145 families with both breast and ovarian cancer . |
[
{
"name": "breast cancer",
"pos": [
102,
115
],
"type": "Disease"
},
{
"name": "ovarian cancer",
"pos": [
119,
133
],
"type": "Disease"
}
] | These families contain either a total of three or more cases of early - onset ( before age 60 years ) breast cancer or ovarian cancer . |
[
{
"name": "ovarian cancer",
"pos": [
44,
58
],
"type": "Disease"
}
] | All families contained at least one case of ovarian cancer . |
[] | Overall , an estimated 76 % of the 145 families are linked to the BRCA1 locus . |
[
{
"name": "male breast cancer",
"pos": [
38,
56
],
"type": "Disease"
},
{
"name": "male breast cancer",
"pos": [
171,
189
],
"type": "Disease"
},
{
"name": "ovarian cancers",
"pos": [
211,
226
],
"type": "Disease"
}
] | None of the 13 families with cases of male breast cancer appear to be linked , but it is estimated that 92 % ( 95 % confidence interval 76 % - 100 % ) of families with no male breast cancer and with two or more ovarian cancers are linked to BRCA1 . |