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[] | We compared galactose - 1 - phosphate uridyltransferase among erythrocytes , leukocytes , and transformed lymphoblasts , as well as total body oxidation of D - ( 13C ) - galactose to 13CO2 among three genotypes for GALT ( S135L / S135L , Q188R / Q188R , and Normal / Normal ) . |
[
{
"name": "classic galactosemia",
"pos": [
95,
115
],
"type": "Disease"
},
{
"name": "galactosemia",
"pos": [
183,
195
],
"type": "Disease"
}
] | RESULTS We found a 48 % prevalence of the S135L mutation among 17 black American patients with classic galactosemia and a 1 % prevalence in a population of 50 black Americans without galactosemia . |
[
{
"name": "galactosemia",
"pos": [
65,
77
],
"type": "Disease"
},
{
"name": "galactosemia",
"pos": [
119,
131
],
"type": "Disease"
}
] | The S135L mutation was not found in 84 white patients with G / G galactosemia nor in 87 white control subjects without galactosemia . |
[] | We found normal whole body oxidation of D - ( 13C ) - galactose by the patient homozygous for S135L and various degrees of enzyme impairment among different tissues . |
[
{
"name": "galactosemia",
"pos": [
72,
84
],
"type": "Disease"
}
] | CONCLUSIONS The S135L mutation in the GALT gene is a prevalent cause of galactosemia among black patients . |
[] | Because GALT activity varies in different tissues of patients homozygous for S135L , they may have a better clinical outcome than patients who are homozygous for Q188R when both are treated from infancy . . |
[
{
"name": "breast - ovarian cancer",
"pos": [
42,
65
],
"type": "Disease"
}
] | A high incidence of BRCA1 mutations in 20 breast - ovarian cancer families . |
[
{
"name": "breast - ovarian cancer",
"pos": [
20,
43
],
"type": "Disease"
}
] | We have analyzed 20 breast - ovarian cancer families , the majority of which show positive evidence of linkage to chromosome 17q12 for germ - line mutations in the BRCA1 gene . |
[
{
"name": "breast and ovarian cancer",
"pos": [
35,
60
],
"type": "Disease"
},
{
"name": "male breast cancer",
"pos": [
143,
161
],
"type": "Disease"
}
] | BRCA1 mutations cosegregating with breast and ovarian cancer susceptibility were identified in 16 families , including 1 family with a case of male breast cancer . |
[] | Nine of these mutations have not been reported previously . |
[] | The majority of mutations were found to generate a premature stop codon leading to the formation of a truncated BRCA1 protein of 2 % - 88 % of the expected normal length . |
[] | Two mutations altered the RING finger domain . |
[] | Sequencing of genomic DNA led to the identification of a mutation in the coding region of BRCA1 in 12 families , and cDNA analysis revealed an abnormal or missing BRCA1 transcript in 4 of the 8 remaining families . |
[] | A total of eight mutations were associated with a reduced quantity of BRCA1 transcript . |
[] | We were unable to detect BRCA1 mutations in 4 of the 20 families , but only 1 of these was clearly linked to BRCA1 . |
[
{
"name": "breast - ovarian syndrome",
"pos": [
58,
83
],
"type": "Disease"
}
] | It is expected that the majority of clear examples of the breast - ovarian syndrome will be associated with germ - line mutations in the coding region of BRCA1 . . |
[
{
"name": "Brca1 deficiency",
"pos": [
0,
16
],
"type": "Disease"
},
{
"name": "embryonic lethality",
"pos": [
34,
53
],
"type": "Disease"
},
{
"name": "neuroepithelial abnormalities",
"pos": [
71,
100
],
"type": "Disease"
}
] | Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities . |
[
{
"name": "breast and ovarian cancer",
"pos": [
4,
29
],
"type": "Disease"
}
] | The breast and ovarian cancer susceptibility gene , BRCA1 , has been cloned and shown to encode a zinc - finger protein of unknown function . |
[
{
"name": "breast and ovarian cancer",
"pos": [
67,
92
],
"type": "Disease"
},
{
"name": "ovarian cancers",
"pos": [
135,
150
],
"type": "Disease"
}
] | Mutations in BRCA1 account for at least 80 % of families with both breast and ovarian cancer , as well as some non - familial sporadic ovarian cancers . |
[
{
"name": "tumours",
"pos": [
33,
40
],
"type": "Disease"
},
{
"name": "tumour",
"pos": [
126,
132
],
"type": "Disease"
}
] | The loss of wild - type BRCA1 in tumours of individuals carrying one nonfunctional BRCA1 allele suggests that BRCA1 encodes a tumour suppressor that may inhibit the proliferation of mammary epithelial cells . |
[
{
"name": "cancer",
"pos": [
117,
123
],
"type": "Disease"
}
] | To examine the role of BRCA1 in normal tissue growth and differentiation , and to generate a potential model for the cancer susceptibility associated with loss of BRCA1 function , we have created a mouse line carrying a mutation in one Brca1 allele . |
[] | Analysis of mice homozygous for the mutant allele indicate that Brca1 is critical for normal development , as these mice died in utero between 10 and 13 days of gestation ( E10 - E13 ) . |
[
{
"name": "Brca1 - deficient",
"pos": [
17,
34
],
"type": "Disease"
},
{
"name": "spina bifida",
"pos": [
142,
154
],
"type": "Disease"
},
{
"name": "anencephaly",
"pos": [
159,
170
],
"type": "Disease"
}
] | Abnormalities in Brca1 - deficient embryos were most evident in the neural tube , with 40 % of the embryos presenting with varying degrees of spina bifida and anencephaly . |
[
{
"name": "Brca1 - deficient",
"pos": [
37,
54
],
"type": "Disease"
}
] | In addition , the neuroepithelium in Brca1 - deficient embryos appeared disorganized , with signs of both rapid proliferation and excessive cell death . . |
[
{
"name": "adrenoleukodystrophy",
"pos": [
66,
86
],
"type": "Disease"
},
{
"name": "adrenomyeloneuropathy",
"pos": [
89,
110
],
"type": "Disease"
}
] | Identification of mutations in the ALD - gene of 20 families with adrenoleukodystrophy / adrenomyeloneuropathy . |
[
{
"name": "Adrenoleukodystrophy",
"pos": [
0,
20
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
23,
26
],
"type": "Disease"
},
{
"name": "X - linked inherited metabolic disorder",
"pos": [
34,
73
],
"type": "Disease"
},
{
"name": "inborn peroxisomal disease",
"pos": [
97,
123
],
"type": "Disease"
}
] | Adrenoleukodystrophy ( ALD ) , an X - linked inherited metabolic disorder , is the most frequent inborn peroxisomal disease . |
[
{
"name": "demyelination in the central and peripheral nervous system",
"pos": [
12,
70
],
"type": "Disease"
}
] | It leads to demyelination in the central and peripheral nervous system . |
[] | Defective beta - oxidation of saturated very long chain fatty acids ( VLCFAs ; C22 0 - C26 0 ) in peroxisomes has been shown to lead to an accumulation of VLCFAs in leukoid areas of the central nervous system , peripheral nerves , adrenal gland , and blood . |
[
{
"name": "ALD",
"pos": [
4,
7
],
"type": "Disease"
}
] | The ALD gene has been recently identified and encodes a 745 - amino - acid protein . |
[
{
"name": "adrenoleukodystrophy",
"pos": [
26,
46
],
"type": "Disease"
},
{
"name": "adrenomyeloneuropathy",
"pos": [
49,
70
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
73,
76
],
"type": "Disease"
},
{
"name": "AMN",
"pos": [
79,
82
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
123,
126
],
"type": "Disease"
}
] | We screened patients with adrenoleukodystrophy / adrenomyeloneuropathy ( ALD / AMN ) from 20 kindreds for mutations in the ALD gene . |
[
{
"name": "ALD",
"pos": [
161,
164
],
"type": "Disease"
}
] | Eleven missense and two nonsense mutations , five deletions , and one insertion were detected by direct sequencing of eight reverse transcribed fragments of the ALD - gene mRNA . |
[] | Four mutations could be shown to be de novo . |
[] | All mutations could be confirmed in carriers by sequencing genomic DNA . |
[] | No correlation between the type of mutation and the severity of the phenotype could be observed . |
[
{
"name": "ALD",
"pos": [
39,
42
],
"type": "Disease"
}
] | The mutations were not detected in the ALD gene of 30 healthy persons . . |
[
{
"name": "breast and ovarian cancer",
"pos": [
32,
57
],
"type": "Disease"
}
] | The murine homolog of the human breast and ovarian cancer susceptibility gene Brca1 maps to mouse chromosome 11D . |
[
{
"name": "breast and ovarian cancer",
"pos": [
26,
51
],
"type": "Disease"
}
] | The recently cloned human breast and ovarian cancer susceptibility gene , BRCA1 , is located on human chromosome 17q21 . |
[] | We have isolated murine genomic clones containing Brca1 as a first step in generating a mouse model for the loss of BRCA1 function . |
[] | A mouse genomic library was screened using probes corresponding to exon 11 of the human BRCA1 gene . |
[] | Two overlapping mouse clones were identified that hybridized to human BRCA1 exons 9 - 12 . |
[] | Sequence analysis of 1 . |
[] | 4 kb of the region of these clones corresponding to part of human exon 11 revealed 72 % nucleic acid identity but only 50 % amino acid identity with the human gene . |
[] | The longest of the mouse Brca1 genomic clones maps to chromosome 11D , as determined by two - color fluorescence in situ hybridization . |
[] | The synteny to human chromosome 17 was confirmed by cohybridization with the mouse probe for the NF1 - gene . |
[] | This comparative study confirms that the relative location of the BRCA1 gene has been conserved between mice and humans . |
[
{
"name": "Atelosteogenesis type II",
"pos": [
0,
24
],
"type": "Disease"
},
{
"name": "diastrophic dysplasia",
"pos": [
55,
76
],
"type": "Disease"
},
{
"name": "chondrodysplasias",
"pos": [
165,
182
],
"type": "Disease"
}
] | Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate - transporter gene ( DTDST ) : evidence for a phenotypic series involving three chondrodysplasias . |
[
{
"name": "Atelosteogenesis type II",
"pos": [
0,
24
],
"type": "Disease"
},
{
"name": "AO II",
"pos": [
27,
32
],
"type": "Disease"
},
{
"name": "chondrodysplasia",
"pos": [
58,
74
],
"type": "Disease"
},
{
"name": "chondrodysplasia",
"pos": [
149,
165
],
"type": "Disease"
},
{
"name": "diastrophic dysplasia",
"pos": [
189,
210
],
"type": "Disease"
},
{
"name": "DTD",
"pos": [
213,
216
],
"type": "Disease"
}
] | Atelosteogenesis type II ( AO II ) is a neonatally lethal chondrodysplasia whose clinical and histological characteristics resemble those of another chondrodysplasia , the much less severe diastrophic dysplasia ( DTD ) . |
[] | The similarity suggests a shared pathogenesis involving lesions in the same biochemical pathway and perhaps the same gene . |
[
{
"name": "DTD",
"pos": [
0,
3
],
"type": "Disease"
},
{
"name": "diastrophic dysplasia",
"pos": [
54,
75
],
"type": "Disease"
}
] | DTD is caused by mutations in the recently identified diastrophic dysplasia sulfate - transporter gene ( DTDST ) . |
[
{
"name": "AOII",
"pos": [
22,
26
],
"type": "Disease"
}
] | Here , we report that AOII patients also have DTDST mutations , which lead to defective uptake of inorganic sulfate and insufficient sulfation of macromolecules by patient mesenchymal cells in vitro . |
[
{
"name": "chondrodysplasia",
"pos": [
67,
83
],
"type": "Disease"
},
{
"name": "chondrodysplasias",
"pos": [
206,
223
],
"type": "Disease"
}
] | Together with our recent observation that a third even more severe chondrodysplasia , achondrogenesis type IB , is also caused by mutations in DTDST , these results demonstrate a phenotypic series of three chondrodysplasias of increasing severity caused by lesions in a single sulfate - transporter gene . |
[] | The severity of the phenotype appears to be correlated with the predicted effect of the mutations on the residual activity of the DTDST protein . . |
[] | Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families : results of an international study . |
[
{
"name": "breast and ovarian cancer",
"pos": [
79,
104
],
"type": "Disease"
}
] | Several BRCA1 mutations have now been found to occur in geographically diverse breast and ovarian cancer families . |
[
{
"name": "breast / ovarian cancer",
"pos": [
198,
221
],
"type": "Disease"
}
] | To investigate mutation origin and mutation - specific phenotypes due to BRCA1 , we constructed a haplotype of nine polymorphic markers within or immediately flanking the BRCA1 locus in a set of 61 breast / ovarian cancer families selected for having one of six recurrent BRCA1 mutations . |
[] | Tests of both mutations and family - specific differences in age at diagnosis were not significant . |
[
{
"name": "breast and ovarian cancer",
"pos": [
74,
99
],
"type": "Disease"
},
{
"name": "ovarian cancer",
"pos": [
230,
244
],
"type": "Disease"
}
] | A comparison of the six mutations in the relative proportions of cases of breast and ovarian cancer was suggestive of an effect ( P = . 069 ) , with 57 % of women presumed affected because of the 1294 del 40 BRCA1 mutation having ovarian cancer , compared with 14 % of affected women with the splice - site mutation in intron 5 of BRCA1 . |
[] | For the BRCA1 mutations studied here , the individual mutations are estimated to have arisen 9 - 170 generations ago . |
[] | In general , a high degree of haplotype conservation across the region was observed , with haplotype differences most often due to mutations in the short - tandem - repeat markers , although some likely instances of recombination also were observed . |
[] | For several of the instances , there was evidence for multiple , independent , BRCA1 mutational events . |
[] | Isolation of the mouse homologue of BRCA1 and genetic mapping to mouse chromosome 11 . |
[
{
"name": "hereditary human breast and ovarian cancer",
"pos": [
48,
90
],
"type": "Disease"
}
] | The BRCA1 gene is in large part responsible for hereditary human breast and ovarian cancer . |
[] | Here we report the isolation of the murine Brca1 homologue cDNA clones . |
[] | In addition , we identified genomic P1 clones that contain most , if not all , of the mouse Brca1 locus . |
[] | DNA sequence analysis revealed that the mouse and human coding regions are 75 % identical at the nucleotide level while the predicted amino acid identity is only 58 % . |
[] | A DNA sequence variant in the Brca1 locus was identified and used to map this gene on a ( Mus m . musculus Czech II x C57BL / KsJ ) F1 x C57BL / KsJ intersubspecific backcross to distal mouse chromosome 11 . |
[] | The mapping of this gene to a region highly syntenic with human chromosome 17 , coupled with Southern and Northern analyses , confirms that we isolated the murine Brca1 homologue rather than a related RING finger gene . |
[
{
"name": "BRCA1 defects",
"pos": [
101,
114
],
"type": "Disease"
}
] | The isolation of the mouse Brca1 homologue will facilitate the creation of mouse models for germline BRCA1 defects . . |
[
{
"name": "Emerin deficiency",
"pos": [
0,
17
],
"type": "Disease"
},
{
"name": "Emery - Dreifuss muscular dystrophy",
"pos": [
59,
94
],
"type": "Disease"
}
] | Emerin deficiency at the nuclear membrane in patients with Emery - Dreifuss muscular dystrophy . |
[
{
"name": "X - linked Emery - Dreifuss muscular dystrophy",
"pos": [
77,
123
],
"type": "Disease"
},
{
"name": "EDMD",
"pos": [
126,
130
],
"type": "Disease"
}
] | Mutations in the STA gene at the Xq28 locus have been found in patients with X - linked Emery - Dreifuss muscular dystrophy ( EDMD ) . |
[] | This gene encodes a hitherto unknown protein named emerin . |
[] | To elucidate the subcellular localization of emerin , we raised two antisera against synthetic peptide fragments predicted from emerin cDNA . |
[
{
"name": "neuromuscular diseases",
"pos": [
151,
173
],
"type": "Disease"
},
{
"name": "EDMD",
"pos": [
185,
189
],
"type": "Disease"
}
] | Using both antisera , we found positive nuclear membrane staining in skeletal , cardiac and smooth muscles in the normal controls and in patients with neuromuscular diseases other than EDMD . |
[
{
"name": "EDMD",
"pos": [
93,
97
],
"type": "Disease"
}
] | In contrast , a deficiency in immunofluorescent staining of skeletal and cardiac muscle from EDMD patients was observed . |
[] | A 34 kD protein is immunoreactive with the antisera - - the protein is equivalent to that predicted for emerin . |
[
{
"name": "deficiency of emerin",
"pos": [
45,
65
],
"type": "Disease"
},
{
"name": "EDMD",
"pos": [
123,
127
],
"type": "Disease"
}
] | Together , our findings suggest the specific deficiency of emerin in the nuclear membrane of muscle cells in patients with EDMD . . |
[
{
"name": "Growth retardation",
"pos": [
0,
18
],
"type": "Disease"
},
{
"name": "tumour",
"pos": [
23,
29
],
"type": "Disease"
}
] | Growth retardation and tumour inhibition by BRCA1 . |
[
{
"name": "breast and ovarian cancer",
"pos": [
43,
68
],
"type": "Disease"
},
{
"name": "breast and ovarian cancer",
"pos": [
105,
130
],
"type": "Disease"
}
] | Inherited mutations in BRCA1 predispose to breast and ovarian cancer , but the role of BRCA1 in sporadic breast and ovarian cancer has previously been elusive . |
[
{
"name": "breast and ovarian cancer",
"pos": [
102,
127
],
"type": "Disease"
},
{
"name": "colon or lung cancer",
"pos": [
156,
176
],
"type": "Disease"
}
] | Here , we show that retroviral transfer of the wild - type BRCA1 gene inhibits growth in vitro of all breast and ovarian cancer cell lines tested , but not colon or lung cancer cells or fibroblasts . |
[
{
"name": "breast cancer",
"pos": [
40,
53
],
"type": "Disease"
},
{
"name": "ovarian cancer",
"pos": [
62,
76
],
"type": "Disease"
}
] | Mutant BRCA1 has no effect on growth of breast cancer cells ; ovarian cancer cell growth is not affected by BRCA1 mutations in the 5 portion of the gene , but is inhibited by 3 BRCA1 mutations . |
[
{
"name": "MCF - 7 tumours",
"pos": [
15,
30
],
"type": "Disease"
}
] | Development of MCF - 7 tumours in nude mice is inhibited when MCF - 7 cells are transfected with wild - type , but not mutant , BRCA1 . |
[
{
"name": "MCF - 7 tumours",
"pos": [
47,
62
],
"type": "Disease"
},
{
"name": "tumour",
"pos": [
163,
169
],
"type": "Disease"
}
] | Most importantly , among mice with established MCF - 7 tumours , peritoneal treatment with a retroviral vector expressing wild - type BRCA1 significantly inhibits tumour growth and increased survival . . |