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[] | A physical map and candidate genes in the BRCA1 region on chromosome 17q12 - 21 . |
[
{
"name": "hereditary breast and ovarian cancer",
"pos": [
95,
131
],
"type": "Disease"
}
] | We have constructed a physical map of a 4 cM region on chromosome 17q12 - 21 that contains the hereditary breast and ovarian cancer gene BRCA1 . |
[] | The map comprises a contig of 137 overlapping yeast artificial chromosomes and P1 clones , onto which we have placed 112 PCR markers . |
[] | We have localized more than 20 genes on this map , ten of which had not been mapped to the region previously , and have isolated 30 cDNA clones representing partial sequences of as yet unidentified genes . |
[
{
"name": "breast cancer",
"pos": [
114,
127
],
"type": "Disease"
}
] | Two genes that lie within a narrow region defined by meiotic breakpoints in BRCA1 patients have been sequenced in breast cancer patients without revealing any deleterious mutations . |
[] | These new reagents should facilitate the identification of BRCA1 . . |
[
{
"name": "Wilson disease",
"pos": [
84,
98
],
"type": "Disease"
}
] | The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene . |
[
{
"name": "Wilson disease",
"pos": [
58,
72
],
"type": "Disease"
}
] | The Long - Evans Cinnamon ( LEC ) rat shows similarity to Wilson disease in many clinical and biochemical features . |
[
{
"name": "Wilson disease",
"pos": [
72,
86
],
"type": "Disease"
}
] | We have cloned cDNAs for the rat gene ( Atp7b ) homologous to the human Wilson disease gene ( ATP7B ) and have used them to identify a partial deletion in the Atp7b gene in the LEC rat . |
[] | The deletion removes at least 900 bp of the coding region at the 3 end , includes the crucial ATP binding domain and extends downstream of the gene . |
[
{
"name": "Wilson disease",
"pos": [
88,
102
],
"type": "Disease"
}
] | Our results provide convincing evidence for defining the LEC rat as an animal model for Wilson disease . |
[
{
"name": "Wilson disease",
"pos": [
93,
107
],
"type": "Disease"
}
] | This model will be important for studying liver pathophysiology , for developing therapy for Wilson disease and for studying the pathway of copper transport and its possible interaction with other heavy metals . . |
[
{
"name": "adrenoleukodystrophy",
"pos": [
28,
48
],
"type": "Disease"
}
] | Genomic organization of the adrenoleukodystrophy gene . |
[
{
"name": "Adrenoleukodystrophy",
"pos": [
0,
20
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
23,
26
],
"type": "Disease"
},
{
"name": "peroxisomal disorder",
"pos": [
49,
69
],
"type": "Disease"
},
{
"name": "neurodegenerative disease",
"pos": [
84,
109
],
"type": "Disease"
},
{
"name": "impairment of very long chain fatty acids beta - oxidation",
"pos": [
129,
187
],
"type": "Disease"
}
] | Adrenoleukodystrophy ( ALD ) , the most frequent peroxisomal disorder , is a severe neurodegenerative disease associated with an impairment of very long chain fatty acids beta - oxidation . |
[
{
"name": "ALD",
"pos": [
75,
78
],
"type": "Disease"
}
] | We have recently identified by positional cloning the gene responsible for ALD , located in Xq28 . |
[] | It encodes a new member of the " ABC " superfamily of membrane - associated transporters that shows , in particular , significant homology to the 70 - kDa peroxisomal membrane protein ( PMP70 ) . |
[
{
"name": "ALD",
"pos": [
50,
53
],
"type": "Disease"
}
] | We report here a detailed characterization of the ALD gene structure . |
[] | It extends over 21 kb and consists of 10 exons . |
[
{
"name": "ALD",
"pos": [
44,
47
],
"type": "Disease"
}
] | To facilitate the detection of mutations in ALD patients , we have determined the intronic sequences flanking the exons as well as the sequence of the 3 untranslated region and of the immediate 5 promoter region . |
[] | Sequences present in distal exons cross - hybridize strongly to additional sequences in the human genome . |
[
{
"name": "ALD",
"pos": [
4,
7
],
"type": "Disease"
}
] | The ALD gene has been positioned on a pulsed - field map between DXS15 and the L1CAM gene , about 650 kb upstream from the color pigment genes . |
[
{
"name": "adrenomyeloneuropathy",
"pos": [
76,
97
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
124,
127
],
"type": "Disease"
},
{
"name": "contiguous gene syndrome",
"pos": [
156,
180
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
214,
217
],
"type": "Disease"
}
] | The frequent occurrence of color vision anomalies observed in patients with adrenomyeloneuropathy ( the adult onset form of ALD ) thus does not represent a contiguous gene syndrome but a secondary manifestation of ALD . . |
[
{
"name": "Huntington disease",
"pos": [
29,
47
],
"type": "Disease"
}
] | The murine homologues of the Huntington disease gene ( Hdh ) and the alpha - adducin gene ( Add1 ) map to mouse chromosome 5 within a region of conserved synteny with human chromosome 4p16 . 3 . |
[
{
"name": "Huntington disease",
"pos": [
0,
18
],
"type": "Disease"
},
{
"name": "HD",
"pos": [
21,
23
],
"type": "Disease"
},
{
"name": "autosomal dominant neurodegenerative disorder",
"pos": [
38,
83
],
"type": "Disease"
}
] | Huntington disease ( HD ) is a severe autosomal dominant neurodegenerative disorder associated with a novel gene ( IT15 ) . |
[] | Recently , we reported the cloning of Hdh , the murine homologue of IT15 . |
[] | Here , using an interspecific backcross , we have mapped both Hdh and the mouse homologue of human alpha - adducin ( Add1 ) , a membrane - associated cytoskeletal protein gene . |
[] | Both of these genes map in the same position on mouse chromosome 5 in a region associated with ancestral chromosomal rearrangements and show no recombination with D5H4S43 , D5H4S115 , and D5H4S62 , the murine homologues of D4S43 , D4S115 , and D4S62 , respectively . |
[] | Further mapping studies of humans , mice , and other mammalian species should reveal the nature of the rearrangements affecting this chromosomal segment during mammalian evolution . . |
[
{
"name": "cholesteryl ester transfer protein deficiency",
"pos": [
8,
53
],
"type": "Disease"
}
] | Genetic cholesteryl ester transfer protein deficiency caused by two prevalent mutations as a major determinant of increased levels of high density lipoprotein cholesterol . |
[] | Genetic determinants of HDL cholesterol ( HDL - C ) levels in the general population are poorly understood . |
[
{
"name": "cholesteryl ester transfer protein ( CETP ) deficiency",
"pos": [
31,
85
],
"type": "Disease"
}
] | We previously described plasma cholesteryl ester transfer protein ( CETP ) deficiency due to an intron 14 G ( + 1 ) - to - A mutation ( Int14 A ) in several families with very high HDL - C levels in Japan . |
[] | Subjects with HDL - C > or = 100 mg / dl ( n = 130 ) were screened by PCR single strand conformational polymorphism analysis of the CETP gene . |
[] | Two other mutations were identified by DNA sequencing or primer - mediated restriction map modification of PCR products a novel intron 14 splice donor site mutation caused by a T insertion at position + 3 from the exon14 / intron14 boundary ( Int14 T ) and a missense mutation ( Asp442 to Gly ) within exon 15 ( D442G ) . |
[] | The Int14 T mutation was only found in one family . |
[] | However , the D442G and Int14 A mutations were highly prevalent in subjects with HDL - C > or = 60 mg / dl , with combined allele frequencies of 9 % , 12 % , 21 % and 43 % for HDL - C 60 - 79 , 80 - 99 , 100 - 119 , and > or = 120 mg / dl , respectively . |
[] | Furthermore , prevalences of the D442G and Int14 A mutations were extremely high in a general sample of Japanese men ( n = 236 ) , with heterozygote frequencies of 7 % and 2 % , respectively . |
[] | These two mutations accounted for about 10 % of the total variance of HDL - C in this population . |
[] | The phenotype in a genetic compound heterozygote ( Int14 T and Int14 A ) was similar to that of Int14 A homozygotes ( no detectable CETP and markedly increased HDL - C ) , indicating that the Int14 T produces a null allele . |
[] | In four D442G homozygotes , mean HDL - C levels ( 86 + / - 26 mg / dl ) were lower than in Int14 A homozygotes ( 158 + / - 35 mg / dl ) , reflecting residual CETP activity in plasma . |
[] | In 47 D442G heterozygotes , mean HDL - C levels were 91 + / - 23 mg / dl , similar to the level in D442G homozygotes , and significantly greater than mean HDL - C levels in Int14 A heterozygotes ( 69 + / - 15 mg / dl ) . |
[] | Thus , the D442G mutation acts differently to the null mutations with weaker effects on HDL in the homozygous state and stronger effects in the heterozygotes , suggesting dominant expression of a partially defective allele . |
[
{
"name": "CETP deficiency",
"pos": [
0,
15
],
"type": "Disease"
},
{
"name": "genetic deficiency",
"pos": [
103,
121
],
"type": "Disease"
}
] | CETP deficiency , reflecting two prevalent mutations ( D442G and Int14 A ) , is the first example of a genetic deficiency state which is sufficiently common to explain a significant fraction of the variation in HDL - C in the general population . . |
[
{
"name": "cerebrotendinous xanthomatosis",
"pos": [
13,
43
],
"type": "Disease"
}
] | Treatment of cerebrotendinous xanthomatosis : effects of chenodeoxycholic acid , pravastatin , and combined use . |
[
{
"name": "cerebrotendinous xanthomatosis",
"pos": [
233,
263
],
"type": "Disease"
},
{
"name": "CTX",
"pos": [
266,
269
],
"type": "Disease"
}
] | Treatments by oral administration of chenodeoxycholic acid ( CDCA ) alone , 3 - hydroxy - 3 - methylglutaryl ( HMG ) CoA reductase inhibitor ( pravastatin ) alone , and combination of the two drugs were attempted for 7 patients with cerebrotendinous xanthomatosis ( CTX ) . |
[] | CDCA treatment at a dose of 300 mg / day reduced serum cholestanol ( 67 . 3 % reduction ) , lathosterol ( 50 . 8 % ) , campesterol ( 61 . 7 % ) and sitosterol ( 12 . 7 % ) . |
[] | However , the sera of the patients changed to be " atherogenic " ; total cholesterol , triglyceride and low - density lipoprotein ( LDL ) - cholesterol were increased , while high - density lipoprotein ( HDL ) - cholesterol was decreased . |
[] | Contrarily , pravastatin at a dose of 10 mg / day improved the sera of the patients to be markedly " anti - atherogenic " , but the reductions of cholestanol ( 30 . 4 % ) , lathosterol ( 44 . 0 % ) , campesterol ( 22 . 9 % ) and sitosterol ( 9 . 6 % ) were inadequate . |
[] | Combined treatment with CDCA and pravastatin showed good overlapping of the effects of each drug alone . |
[] | The sera of the patients were apparently more " anti - atherogenic " than those after CDCA treatment . |
[] | Serum cholestanol concentration was still 2 . |
[] | 7 times higher than in controls , but the serum lathosterol level was within the normal range , indicating that the enhancement of overall cholesterol synthesis in the patients was sufficiently suppressed . |
[] | Plant sterol levels were also within the normal range . |
[
{
"name": "CTX",
"pos": [
65,
68
],
"type": "Disease"
}
] | The combination of CDCA and pravastatin was a good treatment for CTX , based on the improvement of serum lipoprotein metabolism , the suppression of cholesterol synthesis , and reductions of cholestanol and plant sterol levels . |
[
{
"name": "xanthoma",
"pos": [
115,
123
],
"type": "Disease"
}
] | In all of 7 patients , the progression of disease was arrested , but dramatic effects on clinical manifestations , xanthoma , and electrophysiological findings could not be found after the treatment of these drugs |
[
{
"name": "CHM",
"pos": [
25,
28
],
"type": "Disease"
},
{
"name": "choroideremia",
"pos": [
56,
69
],
"type": "Disease"
}
] | Mutation spectrum in the CHM gene of Danish and Swedish choroideremia patients . |
[
{
"name": "choroideremia",
"pos": [
63,
76
],
"type": "Disease"
},
{
"name": "CHM",
"pos": [
79,
82
],
"type": "Disease"
},
{
"name": "choroideremia",
"pos": [
214,
227
],
"type": "Disease"
}
] | The recent isolation of the complete open reading frame of the choroideremia ( CHM ) gene and the characterization of the exon - intron boundaries has paved the way to mutation detection in patients with classical choroideremia . |
[] | We have performed mutation screening in patients from 15 Danish and Swedish families by using Southern blot hybridization and the polymerase chain reaction single - strand conformation polymorphism ( PCR - SSCP ) technique . |
[
{
"name": "CHM",
"pos": [
27,
30
],
"type": "Disease"
}
] | Causative mutations in the CHM gene were detected in at least 12 families , indicating that a substantial part of the mutations can be identified by this approach . |
[] | In four of these families deletions of different sizes were found . |
[
{
"name": "CHM",
"pos": [
131,
134
],
"type": "Disease"
}
] | Thus , in one patient , the deletion resulted in the absence of only one exon , while in another the deletion comprised the entire CHM gene . |
[] | Mapping of the deletion endpoints in these four patients and in another 11 male patients with sizeable deletions enabled us to construct a very detailed map of intervals 2 and 3 of Xq21 . |
[] | In the remaining 11 Danish and Swedish families at least 8 causative mutations were found by PCR - SSCP analysis and direct sequencing . |
[
{
"name": "CHM",
"pos": [
20,
23
],
"type": "Disease"
},
{
"name": "choroideremia",
"pos": [
60,
73
],
"type": "Disease"
}
] | Interestingly , all CHM gene mutations detected thus far in choroideremia patients give rise to the introduction of a premature stop codon . . |
[
{
"name": "adrenomyeloneuropathy",
"pos": [
20,
41
],
"type": "Disease"
},
{
"name": "X - linked adrenoleukodystrophy",
"pos": [
55,
86
],
"type": "Disease"
}
] | Predominance of the adrenomyeloneuropathy phenotype of X - linked adrenoleukodystrophy in The Netherlands : a survey of 30 kindreds . |
[
{
"name": "X - linked adrenoleukodystrophy",
"pos": [
0,
31
],
"type": "Disease"
},
{
"name": "X - ALD",
"pos": [
34,
41
],
"type": "Disease"
},
{
"name": "inherited disorder",
"pos": [
50,
68
],
"type": "Disease"
},
{
"name": "demyelination",
"pos": [
215,
228
],
"type": "Disease"
},
{
"name": "impaired function of adrenal cortex and testes",
"pos": [
236,
282
],
"type": "Disease"
}
] | X - linked adrenoleukodystrophy ( X - ALD ) is an inherited disorder of peroxisomal beta - oxidation associated with accumulation of saturated very long - chain fatty acids , which results in central and peripheral demyelination and in impaired function of adrenal cortex and testes . |
[
{
"name": "childhood cerebral ALD",
"pos": [
47,
69
],
"type": "Disease"
},
{
"name": "CCALD",
"pos": [
72,
77
],
"type": "Disease"
},
{
"name": "adrenomyeloneuropathy",
"pos": [
84,
105
],
"type": "Disease"
},
{
"name": "AMN",
"pos": [
108,
111
],
"type": "Disease"
}
] | The phenotypic expression is highly variable , childhood cerebral ALD ( CCALD ) and adrenomyeloneuropathy ( AMN ) being the main variants . |
[
{
"name": "X - ALD",
"pos": [
58,
65
],
"type": "Disease"
},
{
"name": "AMN",
"pos": [
68,
71
],
"type": "Disease"
},
{
"name": "AMN",
"pos": [
132,
135
],
"type": "Disease"
},
{
"name": "CCALD",
"pos": [
152,
157
],
"type": "Disease"
},
{
"name": "adolescent cerebral ALD",
"pos": [
161,
184
],
"type": "Disease"
},
{
"name": "AdolCALD",
"pos": [
187,
195
],
"type": "Disease"
}
] | We explored the 30 Dutch kindreds well known to the Dutch X - ALD / AMN Study Group and phenotyped 77 male patients 35 ( 46 % ) had AMN and 24 ( 31 % ) CCALD or adolescent cerebral ALD ( AdolCALD ) . |
[
{
"name": "AMN",
"pos": [
109,
112
],
"type": "Disease"
},
{
"name": "CCALD",
"pos": [
128,
133
],
"type": "Disease"
},
{
"name": "AdolCALD",
"pos": [
137,
145
],
"type": "Disease"
}
] | These percentages differ significantly from previous reports , in which 25 to 28 % of the patients developed AMN and 53 to 57 % CCALD or AdolCALD . |
[
{
"name": "AMN",
"pos": [
63,
66
],
"type": "Disease"
},
{
"name": "X - ALD",
"pos": [
105,
112
],
"type": "Disease"
}
] | Our findings indicate that - - at least in the Netherlands - - AMN may be the most frequent phenotype of X - ALD . . |
[
{
"name": "Adrenoleukodystrophy",
"pos": [
0,
20
],
"type": "Disease"
}
] | Adrenoleukodystrophy gene encodes an 80 kDa membrane protein . |
[
{
"name": "X - linked adrenoleukodystrophy",
"pos": [
106,
137
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
140,
143
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
194,
197
],
"type": "Disease"
}
] | An antibody against the synthetic C - terminal peptides deduced from the cDNA of the gene responsible for X - linked adrenoleukodystrophy ( ALD ) was produced to characterize the product of the ALD gene . |
[
{
"name": "ALD",
"pos": [
143,
146
],
"type": "Disease"
},
{
"name": "ALD",
"pos": [
180,
183
],
"type": "Disease"
}
] | The antibody reacted with the 80 kDa band protein in control fibroblasts , while no bands were detected in the fibroblasts from a patient with ALD ( # 163 ) , in which mRNA of the ALD gene was undetectable based on Northern blot analysis . |
[] | The 293T cells transfected with the full - coding cDNA inserted in the expression vector produced a new 80 kDa protein , as detected by Western blot . |
[] | In an immunocytological study , the staining was in a punctate pattern , in the normal fibroblasts . |
[] | However , there was no punctate staining in the # 163 cells . |
[
{
"name": "ALD",
"pos": [
34,
37
],
"type": "Disease"
}
] | These data thus indicate that the ALD gene encodes an 80 kDa membrane protein . . |
[
{
"name": "McLeod syndrome",
"pos": [
26,
41
],
"type": "Disease"
}
] | Isolation of the gene for McLeod syndrome that encodes a novel membrane transport protein . |
[
{
"name": "McLeod syndrome",
"pos": [
0,
15
],
"type": "Disease"
},
{
"name": "X - linked multisystem disorder",
"pos": [
22,
53
],
"type": "Disease"
}
] | McLeod syndrome is an X - linked multisystem disorder characterized by abnormalities in the neuromuscular and hematopoietic systems . |
[
{
"name": "McLeod",
"pos": [
65,
71
],
"type": "Disease"
}
] | We have assembled a cosmid contig of 360 kb that encompasses the McLeod gene locus . |
[] | A 50 kb deletion was detected by screening DNA from patients with radiolabeled whole cosmids , and two transcription units were identified within this deletion . |
[
{
"name": "McLeod",
"pos": [
90,
96
],
"type": "Disease"
}
] | The mRNA expression pattern of one of them , designated as XK , correlates closely to the McLeod phenotype . |
[] | XK encodes a novel protein with structural characteristics of prokaryotic and eukaryotic membrane transport proteins . |
[
{
"name": "McLeod",
"pos": [
54,
60
],
"type": "Disease"
}
] | Nucleotide sequence analysis of XK from two unrelated McLeod patients has identified point mutations at conserved splice donor and acceptor sites . |
[
{
"name": "McLeod syndrome",
"pos": [
66,
81
],
"type": "Disease"
}
] | These findings provide direct evidence that XK is responsible for McLeod syndrome . . |
[
{
"name": "X - linked spastic paraplegia",
"pos": [
0,
29
],
"type": "Disease"
},
{
"name": "Pelizaeus - Merzbacher disease",
"pos": [
34,
64
],
"type": "Disease"
},
{
"name": "allelic disorders",
"pos": [
69,
86
],
"type": "Disease"
}
] | X - linked spastic paraplegia and Pelizaeus - Merzbacher disease are allelic disorders at the proteolipid protein locus . |
[
{
"name": "X - linked spastic paraplegia",
"pos": [
15,
44
],
"type": "Disease"
},
{
"name": "SPG",
"pos": [
47,
50
],
"type": "Disease"
}
] | Three forms of X - linked spastic paraplegia ( SPG ) have been defined . |
[] | One locus ( SPG 1 ) maps to Xq28 while two clinically distinct forms map to Xq22 ( SPG2 ) . |
[
{
"name": "X - linked dysmyelinating disorder",
"pos": [
7,
41
],
"type": "Disease"
},
{
"name": "Pelizaeus - Merzbacher disease",
"pos": [
74,
104
],
"type": "Disease"
},
{
"name": "PMD",
"pos": [
107,
110
],
"type": "Disease"
}
] | A rare X - linked dysmyelinating disorder of the central nervous system , Pelizaeus - Merzbacher disease ( PMD ) , has also been mapped to Xq21 - q22 , and is caused by mutations in the proteolipid protein gene ( PLP ) which encodes two myelin proteins , PLP and DM20 . |
[] | While narrowing the genetic interval containing SPG2 in a large pedigree , we found that PLP was the closest marker to the disease locus , implicating PLP as a possible candidate gene . |
[] | We have found that a point mutation ( His139Tyr ) in exon 3B of an affected male produces a mutant PLP but a normal DM20 , and segregates with the disease ( Zmax = 6 . 63 , theta = 0 . 00 ) . |
[
{
"name": "PMD",
"pos": [
39,
42
],
"type": "Disease"
}
] | It appears , therefore , that SPG2 and PMD are allelic disorders |
[
{
"name": "Canavan disease",
"pos": [
0,
15
],
"type": "Disease"
}
] | Canavan disease : mutations among Jewish and non - Jewish patients . |
[
{
"name": "Canavan disease",
"pos": [
0,
15
],
"type": "Disease"
},
{
"name": "autosomal recessive leukodystrophy",
"pos": [
22,
56
],
"type": "Disease"
},
{
"name": "deficiency of aspartoacylase",
"pos": [
71,
99
],
"type": "Disease"
}
] | Canavan disease is an autosomal recessive leukodystrophy caused by the deficiency of aspartoacylase ( ASPA ) . |
[] | Sixty - four probands were analyzed for mutations in the ASPA gene . |
[] | Three point mutations - - 693C - - > A , 854A - - > C , and 914C - - > A - - were identified in the coding sequence . |
[] | The 693C - - > A and 914C - - > A base changes , resulting in nonsense tyr231 - - > ter and missense ala305 - - > glu mutations , respectively , lead to complete loss of ASPA activity in in vitro expression studies . |
[] | The 854A - - > C transversion converted glu to ala in codon 285 . |
[] | The glu285 - - > ala mutant ASPA has 2 . |
[] | 5 % of the activity expressed by the wild - type enzyme . |
[] | A fourth mutation , 433 - - 2 ( A - - > G ) transition , was identified at the splice - acceptor site in intron 2 . |