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4
DISCUSSION
1
24–26
[ "B24 B25 B26", "B26", "B45", "B46", "B47" ]
17,483,514
pmid-16547173|pmid-16547172|pmid-11331589|pmid-15043812|pmid-16462942|pmid-16462942|pmid-11331589|pmid-12718883|pmid-15043812|pmid-15043812|pmid-15961632|pmid-8107823|pmid-11583616
However, we found for the first time DH sites common to both sexes that overlapped with DCC recruiting elements, and only two of the five DBFs contained a male-specific DH site.
[ "24–26", "26", "45", "46", "47" ]
177
5,100
0
false
However, we found for the first time DH sites common to both sexes that overlapped with DCC recruiting elements, and only two of the five DBFs contained a male-specific DH site.
[]
However, we found for the first time DH sites common to both sexes that overlapped with DCC recruiting elements, and only two of the five DBFs contained a male-specific DH site.
true
true
true
true
true
847
4
DISCUSSION
1
24–26
[ "B24 B25 B26", "B26", "B45", "B46", "B47" ]
17,483,514
pmid-16547173|pmid-16547172|pmid-11331589|pmid-15043812|pmid-16462942|pmid-16462942|pmid-11331589|pmid-12718883|pmid-15043812|pmid-15043812|pmid-15961632|pmid-8107823|pmid-11583616
The single example of a male-specific DH site tested in the transgenic fly for DCC recruitment was not capable of recruiting the DCC with high affinity, suggesting that male-specific DNase-I hypersensitivity is merely a crude indicator of chromatin accessibility and does not reflect the strength of the underlying seque...
[ "24–26", "26", "45", "46", "47" ]
343
5,101
0
false
The single example of a male-specific DH site tested in the transgenic fly for DCC recruitment was not capable of recruiting the DCC with high affinity, suggesting that male-specific DNase-I hypersensitivity is merely a crude indicator of chromatin accessibility and does not reflect the strength of the underlying seque...
[]
The single example of a male-specific DH site tested in the transgenic fly for DCC recruitment was not capable of recruiting the DCC with high affinity, suggesting that male-specific DNase-I hypersensitivity is merely a crude indicator of chromatin accessibility and does not reflect the strength of the underlying seque...
true
true
true
true
true
847
4
DISCUSSION
1
26
[ "B24 B25 B26", "B26", "B45", "B46", "B47" ]
17,483,514
pmid-16547173|pmid-16547172|pmid-11331589|pmid-15043812|pmid-16462942|pmid-16462942|pmid-11331589|pmid-12718883|pmid-15043812|pmid-15043812|pmid-15961632|pmid-8107823|pmid-11583616
This is similar to the findings of the DBF at 18D, where a male-specific DH site was necessary for high affinity of a larger fragment, but was alone not sufficient (26).
[ "24–26", "26", "45", "46", "47" ]
169
5,102
1
false
This is similar to the findings of the DBF at 18D, where a male-specific DH site was necessary for high affinity of a larger fragment, but was alone not sufficient.
[ "26" ]
This is similar to the findings of the DBF at 18D, where a male-specific DH site was necessary for high affinity of a larger fragment, but was alone not sufficient.
true
true
true
true
true
847
4
DISCUSSION
1
24–26
[ "B24 B25 B26", "B26", "B45", "B46", "B47" ]
17,483,514
pmid-16547173|pmid-16547172|pmid-11331589|pmid-15043812|pmid-16462942|pmid-16462942|pmid-11331589|pmid-12718883|pmid-15043812|pmid-15043812|pmid-15961632|pmid-8107823|pmid-11583616
Conceivably, regulatory elements attracting the DCC in males may have co-opted sequence elements and interacting factors that facilitate chromatin opening, and so perform this function also in females.
[ "24–26", "26", "45", "46", "47" ]
201
5,103
0
false
Conceivably, regulatory elements attracting the DCC in males may have co-opted sequence elements and interacting factors that facilitate chromatin opening, and so perform this function also in females.
[]
Conceivably, regulatory elements attracting the DCC in males may have co-opted sequence elements and interacting factors that facilitate chromatin opening, and so perform this function also in females.
true
true
true
true
true
847
4
DISCUSSION
1
24–26
[ "B24 B25 B26", "B26", "B45", "B46", "B47" ]
17,483,514
pmid-16547173|pmid-16547172|pmid-11331589|pmid-15043812|pmid-16462942|pmid-16462942|pmid-11331589|pmid-12718883|pmid-15043812|pmid-15043812|pmid-15961632|pmid-8107823|pmid-11583616
Accessory elements may therefore not contribute to defining a DBF, but rather facilitate the interaction of the MSLs with DNA in chromatin.
[ "24–26", "26", "45", "46", "47" ]
139
5,104
0
false
Accessory elements may therefore not contribute to defining a DBF, but rather facilitate the interaction of the MSLs with DNA in chromatin.
[]
Accessory elements may therefore not contribute to defining a DBF, but rather facilitate the interaction of the MSLs with DNA in chromatin.
true
true
true
true
true
847
4
DISCUSSION
1
45
[ "B24 B25 B26", "B26", "B45", "B46", "B47" ]
17,483,514
pmid-16547173|pmid-16547172|pmid-11331589|pmid-15043812|pmid-16462942|pmid-16462942|pmid-11331589|pmid-12718883|pmid-15043812|pmid-15043812|pmid-15961632|pmid-8107823|pmid-11583616
For example, runs of poly A/T tend not to be assembled into nucleosomes, which could aid interaction of the DCC (45).
[ "24–26", "26", "45", "46", "47" ]
117
5,105
1
false
For example, runs of poly A/T tend not to be assembled into nucleosomes, which could aid interaction of the DCC.
[ "45" ]
For example, runs of poly A/T tend not to be assembled into nucleosomes, which could aid interaction of the DCC.
true
true
true
true
true
847
4
DISCUSSION
1
24–26
[ "B24 B25 B26", "B26", "B45", "B46", "B47" ]
17,483,514
pmid-16547173|pmid-16547172|pmid-11331589|pmid-15043812|pmid-16462942|pmid-16462942|pmid-11331589|pmid-12718883|pmid-15043812|pmid-15043812|pmid-15961632|pmid-8107823|pmid-11583616
Furthermore, GAGAG sequences are found in many regulatory elements, where the interacting proteins, such as GAF, recruit nucleosome remodelling factors that render nucleosomal DNA accessible (46,47).
[ "24–26", "26", "45", "46", "47" ]
199
5,106
0
false
Furthermore, GAGAG sequences are found in many regulatory elements, where the interacting proteins, such as GAF, recruit nucleosome remodelling factors that render nucleosomal DNA accessible.
[ "46,47" ]
Furthermore, GAGAG sequences are found in many regulatory elements, where the interacting proteins, such as GAF, recruit nucleosome remodelling factors that render nucleosomal DNA accessible.
true
true
true
true
true
847
0
INTRODUCTION
0
null
null
17,158,153
pmid-10869235|pmid-15368617|NA|pmid-16479260|pmid-16909384|NA
The discovery of abundant single-nucleotide polymorphisms (SNPs) in the human genome has driven the development of technologies for rapid and efficient genotyping.
null
163
5,107
0
false
null
null
The discovery of abundant single-nucleotide polymorphisms (SNPs) in the human genome has driven the development of technologies for rapid and efficient genotyping.
true
true
true
true
true
848
0
INTRODUCTION
0
null
null
17,158,153
pmid-10869235|pmid-15368617|NA|pmid-16479260|pmid-16909384|NA
However, a more difficult challenge is to resolve the two haplotypes carried by a diploid individual, determining which alleles lie on each of the two homologous chromosomes.
null
174
5,108
0
false
null
null
However, a more difficult challenge is to resolve the two haplotypes carried by a diploid individual, determining which alleles lie on each of the two homologous chromosomes.
true
true
true
true
true
848
0
INTRODUCTION
0
null
null
17,158,153
pmid-10869235|pmid-15368617|NA|pmid-16479260|pmid-16909384|NA
For instance, an individual may have the genotype AB/ab (heterozygous at each of loci A and B), but could carry haplotypes AB and ab or, conversely, Ab and aB.
null
159
5,109
0
false
null
null
For instance, an individual may have the genotype AB/ab (heterozygous at each of loci A and B), but could carry haplotypes AB and ab or, conversely, Ab and aB.
true
true
true
true
true
848
1
INTRODUCTION
1
1
[ "b1", "b5" ]
17,158,153
pmid-10869235|pmid-15368617
It is increasingly appreciated that haplotypes, rather than genotypes alone, carry the richest data on human variation (1–5).
[ "1", "5" ]
125
5,110
0
false
It is increasingly appreciated that haplotypes, rather than genotypes alone, carry the richest data on human variation.
[ "1–5" ]
It is increasingly appreciated that haplotypes, rather than genotypes alone, carry the richest data on human variation.
true
true
true
true
true
849
1
INTRODUCTION
1
1
[ "b1", "b5" ]
17,158,153
pmid-10869235|pmid-15368617
Quantitative traits such as drug responsiveness or disease susceptibility may be more strongly correlated with certain haplotypes than with certain genotypes, particularly where several polymorphic loci fall within a single gene.
[ "1", "5" ]
229
5,111
0
false
Quantitative traits such as drug responsiveness or disease susceptibility may be more strongly correlated with certain haplotypes than with certain genotypes, particularly where several polymorphic loci fall within a single gene.
[]
Quantitative traits such as drug responsiveness or disease susceptibility may be more strongly correlated with certain haplotypes than with certain genotypes, particularly where several polymorphic loci fall within a single gene.
true
true
true
true
true
849
1
INTRODUCTION
1
1
[ "b1", "b5" ]
17,158,153
pmid-10869235|pmid-15368617
Hence, both the discovery of an association between trait and polymorphism, and the implications of this association for an individual, depend on a knowledge of haplotypes.
[ "1", "5" ]
172
5,112
0
false
Hence, both the discovery of an association between trait and polymorphism, and the implications of this association for an individual, depend on a knowledge of haplotypes.
[]
Hence, both the discovery of an association between trait and polymorphism, and the implications of this association for an individual, depend on a knowledge of haplotypes.
true
true
true
true
true
849
1
INTRODUCTION
1
1
[ "b1", "b5" ]
17,158,153
pmid-10869235|pmid-15368617
Haplotype structure is also important in understanding the evolution of a species and of populations within it, as haplotype blocks are shuffled in successive generations.
[ "1", "5" ]
171
5,113
0
false
Haplotype structure is also important in understanding the evolution of a species and of populations within it, as haplotype blocks are shuffled in successive generations.
[]
Haplotype structure is also important in understanding the evolution of a species and of populations within it, as haplotype blocks are shuffled in successive generations.
true
true
true
true
true
849
1
INTRODUCTION
1
1
[ "b1", "b5" ]
17,158,153
pmid-10869235|pmid-15368617
The persistence of ancestral haplotypes can also be used to simplify genotyping experiments: the genotype at one locus may serve as a proxy for the genotypes of neighbouring loci if they lie within the same conserved haplotype block.
[ "1", "5" ]
233
5,114
0
false
The persistence of ancestral haplotypes can also be used to simplify genotyping experiments: the genotype at one locus may serve as a proxy for the genotypes of neighbouring loci if they lie within the same conserved haplotype block.
[]
The persistence of ancestral haplotypes can also be used to simplify genotyping experiments: the genotype at one locus may serve as a proxy for the genotypes of neighbouring loci if they lie within the same conserved haplotype block.
true
true
true
true
true
849
2
INTRODUCTION
1
6
[ "b6", "b7" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
Classically, haplotypes have been inferred by genotyping several generations of a pedigree and tracing the segregation of markers.
[ "6", "7" ]
130
5,115
0
false
Classically, haplotypes have been inferred by genotyping several generations of a pedigree and tracing the segregation of markers.
[]
Classically, haplotypes have been inferred by genotyping several generations of a pedigree and tracing the segregation of markers.
true
true
true
true
true
850
2
INTRODUCTION
1
6
[ "b6", "b7" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
At a population level, conversely, the abundance of different haplotypes can be estimated from the combined genotype data for many unrelated individualsβ€”one of the aims of the HapMap project [ and Ref.
[ "6", "7" ]
201
5,116
0
false
At a population level, conversely, the abundance of different haplotypes can be estimated from the combined genotype data for many unrelated individualsβ€”one of the aims of the HapMap project [ and Ref.
[]
At a population level, conversely, the abundance of different haplotypes can be estimated from the combined genotype data for many unrelated individualsβ€”one of the aims of the HapMap project [ and Ref.
true
true
true
true
true
850
2
INTRODUCTION
1
6
[ "b6", "b7" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
(6), though see also Ref.
[ "6", "7" ]
25
5,117
1
false
, though see also Ref.
[ "6" ]
, though see also Ref.
false
false
true
true
false
850
2
INTRODUCTION
1
6
[ "b6", "b7" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
Population abundances of haplotypes can also be used to infer individual haplotypes from genotyping data, but only with certain assumptions and only over the very short distances within which recombination can be assumed not to have occurred.
[ "6", "7" ]
242
5,118
0
false
Population abundances of haplotypes can also be used to infer individual haplotypes from genotyping data, but only with certain assumptions and only over the very short distances within which recombination can be assumed not to have occurred.
[]
Population abundances of haplotypes can also be used to infer individual haplotypes from genotyping data, but only with certain assumptions and only over the very short distances within which recombination can be assumed not to have occurred.
true
true
true
true
true
850
2
INTRODUCTION
1
6
[ "b6", "b7" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
None of these approaches, however, can generally be applied diagnostically to resolve long-range haplotypes in a heterozygote in the absence of multi-generational family members.
[ "6", "7" ]
178
5,119
0
false
None of these approaches, however, can generally be applied diagnostically to resolve long-range haplotypes in a heterozygote in the absence of multi-generational family members.
[]
None of these approaches, however, can generally be applied diagnostically to resolve long-range haplotypes in a heterozygote in the absence of multi-generational family members.
true
true
true
true
true
850
3
INTRODUCTION
1
8
[ "b8", "b11", "b12", "b22", "b14" ]
17,158,153
pmid-10693791|pmid-16251461|pmid-2573038|pmid-15637233|pmid-12060700
To overcome these limitations, a number of methods have been proposed to physically resolve the diploid chromosomes of an individual into their haplotypes.
[ "8", "11", "12", "22", "14" ]
155
5,120
0
false
To overcome these limitations, a number of methods have been proposed to physically resolve the diploid chromosomes of an individual into their haplotypes.
[]
To overcome these limitations, a number of methods have been proposed to physically resolve the diploid chromosomes of an individual into their haplotypes.
true
true
true
true
true
851
3
INTRODUCTION
1
8
[ "b8", "b11", "b12", "b22", "b14" ]
17,158,153
pmid-10693791|pmid-16251461|pmid-2573038|pmid-15637233|pmid-12060700
Cloning in hybridomas or in bacterial or yeast cells, or the natural occurrence of hydatidiform moles arising from a single haploid gamete, can be used to isolate a single haplotype which can then be revealed by simple genotyping (8–11).
[ "8", "11", "12", "22", "14" ]
237
5,121
0
false
Cloning in hybridomas or in bacterial or yeast cells, or the natural occurrence of hydatidiform moles arising from a single haploid gamete, can be used to isolate a single haplotype which can then be revealed by simple genotyping.
[ "8–11" ]
Cloning in hybridomas or in bacterial or yeast cells, or the natural occurrence of hydatidiform moles arising from a single haploid gamete, can be used to isolate a single haplotype which can then be revealed by simple genotyping.
true
true
true
true
true
851
3
INTRODUCTION
1
8
[ "b8", "b11", "b12", "b22", "b14" ]
17,158,153
pmid-10693791|pmid-16251461|pmid-2573038|pmid-15637233|pmid-12060700
Such approaches, however, are ill-suited to large-scale studies or to diagnostic screening of individuals.
[ "8", "11", "12", "22", "14" ]
106
5,122
0
false
Such approaches, however, are ill-suited to large-scale studies or to diagnostic screening of individuals.
[]
Such approaches, however, are ill-suited to large-scale studies or to diagnostic screening of individuals.
true
true
true
true
true
851
3
INTRODUCTION
1
8
[ "b8", "b11", "b12", "b22", "b14" ]
17,158,153
pmid-10693791|pmid-16251461|pmid-2573038|pmid-15637233|pmid-12060700
A variety of techniques based on allele-specific PCR, electrophoretic separation of haplotypes or allele-specific hybridisation have been used to detect different haplotypes or to separate haplotypes for later analysis (12–22).
[ "8", "11", "12", "22", "14" ]
227
5,123
0
false
A variety of techniques based on allele-specific PCR, electrophoretic separation of haplotypes or allele-specific hybridisation have been used to detect different haplotypes or to separate haplotypes for later analysis.
[ "12–22" ]
A variety of techniques based on allele-specific PCR, electrophoretic separation of haplotypes or allele-specific hybridisation have been used to detect different haplotypes or to separate haplotypes for later analysis.
true
true
true
true
true
851
3
INTRODUCTION
1
14
[ "b8", "b11", "b12", "b22", "b14" ]
17,158,153
pmid-10693791|pmid-16251461|pmid-2573038|pmid-15637233|pmid-12060700
All of these approaches, however, are limited to the analysis of small numbers of loci over short distances (typically a few hundred base pairs), although it was suggested that some methods could be used to build up longer haplotypes step-wise (14).
[ "8", "11", "12", "22", "14" ]
249
5,124
1
false
All of these approaches, however, are limited to the analysis of small numbers of loci over short distances (typically a few hundred base pairs), although it was suggested that some methods could be used to build up longer haplotypes step-wise.
[ "14" ]
All of these approaches, however, are limited to the analysis of small numbers of loci over short distances (typically a few hundred base pairs), although it was suggested that some methods could be used to build up longer haplotypes step-wise.
true
true
true
true
true
851
4
INTRODUCTION
1
23
[ "b23", "b24", "b25", "b28", "b29", "b31", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
Other methods have been based on the analysis by PCR of single DNA molecules which, of course, represent single haplotypes.
[ "23", "24", "25", "28", "29", "31", "32" ]
123
5,125
0
false
Other methods have been based on the analysis by PCR of single DNA molecules which, of course, represent single haplotypes.
[]
Other methods have been based on the analysis by PCR of single DNA molecules which, of course, represent single haplotypes.
true
true
true
true
true
852
4
INTRODUCTION
1
23
[ "b23", "b24", "b25", "b28", "b29", "b31", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
The most direct implementation of this strategy is the genotyping of single sperm, (23,24) in which meiosis has done the job of isolating a single copy of each chromosome.
[ "23", "24", "25", "28", "29", "31", "32" ]
171
5,126
0
false
The most direct implementation of this strategy is the genotyping of single sperm, in which meiosis has done the job of isolating a single copy of each chromosome.
[ "23,24" ]
The most direct implementation of this strategy is the genotyping of single sperm, in which meiosis has done the job of isolating a single copy of each chromosome.
true
true
true
true
true
852
4
INTRODUCTION
1
23
[ "b23", "b24", "b25", "b28", "b29", "b31", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
Other approaches rely upon limiting dilution to isolate (statistically) single DNA molecules, followed by amplification and genotyping of two or more loci (25–28).
[ "23", "24", "25", "28", "29", "31", "32" ]
163
5,127
0
false
Other approaches rely upon limiting dilution to isolate (statistically) single DNA molecules, followed by amplification and genotyping of two or more loci.
[ "25–28" ]
Other approaches rely upon limiting dilution to isolate (statistically) single DNA molecules, followed by amplification and genotyping of two or more loci.
true
true
true
true
true
852
4
INTRODUCTION
1
23
[ "b23", "b24", "b25", "b28", "b29", "b31", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
However, haplotypes assembled by these techniques rarely exceed 20–30 kb in length (29–31), never involve more than a few loci and the methods are often inefficient, since only a few of the highly dilute samples which are genotyped will prove to contain informative molecules.
[ "23", "24", "25", "28", "29", "31", "32" ]
276
5,128
0
false
However, haplotypes assembled by these techniques rarely exceed 20–30 kb in length, never involve more than a few loci and the methods are often inefficient, since only a few of the highly dilute samples which are genotyped will prove to contain informative molecules.
[ "29–31" ]
However, haplotypes assembled by these techniques rarely exceed 20–30 kb in length, never involve more than a few loci and the methods are often inefficient, since only a few of the highly dilute samples which are genotyped will prove to contain informative molecules.
true
true
true
true
true
852
4
INTRODUCTION
1
32
[ "b23", "b24", "b25", "b28", "b29", "b31", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
An exception is the use of the β€˜polony’ method to genotype intact chromosomal DNA molecules dispersed in an acrylamide film (32).
[ "23", "24", "25", "28", "29", "31", "32" ]
129
5,129
1
false
An exception is the use of the β€˜polony’ method to genotype intact chromosomal DNA molecules dispersed in an acrylamide film.
[ "32" ]
An exception is the use of the β€˜polony’ method to genotype intact chromosomal DNA molecules dispersed in an acrylamide film.
true
true
true
true
true
852
4
INTRODUCTION
1
23
[ "b23", "b24", "b25", "b28", "b29", "b31", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
This elegant technique is efficient and long-range, but requires metaphase cells, careful primer optimisation and again appears to be limited to the analysis of small numbers of loci.
[ "23", "24", "25", "28", "29", "31", "32" ]
183
5,130
0
false
This elegant technique is efficient and long-range, but requires metaphase cells, careful primer optimisation and again appears to be limited to the analysis of small numbers of loci.
[]
This elegant technique is efficient and long-range, but requires metaphase cells, careful primer optimisation and again appears to be limited to the analysis of small numbers of loci.
true
true
true
true
true
852
5
INTRODUCTION
0
null
null
17,158,153
pmid-15875012|NA|pmid-16362058|pmid-16721378
We have devised a molecular haplotyping method which also relies upon limiting dilution but which, for the first time, demonstrates the reconstruction of haplotypes spanning large numbers of loci over long distances, from the DNA of a single individual (Figure 1).
null
264
5,131
0
false
null
null
We have devised a molecular haplotyping method which also relies upon limiting dilution but which, for the first time, demonstrates the reconstruction of haplotypes spanning large numbers of loci over long distances, from the DNA of a single individual (Figure 1).
true
true
true
true
true
853
5
INTRODUCTION
0
null
null
17,158,153
pmid-15875012|NA|pmid-16362058|pmid-16721378
DNA is dispensed at extreme dilution into a panel of aliquots, each containing much less than one genome's worth of DNA.
null
120
5,132
0
false
null
null
DNA is dispensed at extreme dilution into a panel of aliquots, each containing much less than one genome's worth of DNA.
true
true
true
true
true
853
5
INTRODUCTION
0
null
null
17,158,153
pmid-15875012|NA|pmid-16362058|pmid-16721378
Hence, any given segment of the genome will be found in only a minority of the aliquots and, in those aliquots, only one of the two haplotypes is likely to be present.
null
167
5,133
0
false
null
null
Hence, any given segment of the genome will be found in only a minority of the aliquots and, in those aliquots, only one of the two haplotypes is likely to be present.
true
true
true
true
true
853
5
INTRODUCTION
0
null
null
17,158,153
pmid-15875012|NA|pmid-16362058|pmid-16721378
Importantly, an initial pre-screening reveals the precise molecular content of each aliquot.
null
92
5,134
0
false
null
null
Importantly, an initial pre-screening reveals the precise molecular content of each aliquot.
true
true
true
true
true
853
5
INTRODUCTION
0
null
null
17,158,153
pmid-15875012|NA|pmid-16362058|pmid-16721378
From these results, a small subset of aliquots can be selected which are likely to be informative, and only these aliquots need be genotyped for particular loci.
null
161
5,135
0
false
null
null
From these results, a small subset of aliquots can be selected which are likely to be informative, and only these aliquots need be genotyped for particular loci.
true
true
true
true
true
853
5
INTRODUCTION
0
null
null
17,158,153
pmid-15875012|NA|pmid-16362058|pmid-16721378
By genotyping just a few aliquots at each locus, robust haplotypes involving multiple loci can be built up over distances which are not limited by the size of DNA fragments.
null
173
5,136
0
false
null
null
By genotyping just a few aliquots at each locus, robust haplotypes involving multiple loci can be built up over distances which are not limited by the size of DNA fragments.
true
true
true
true
true
853
6
INTRODUCTION
0
null
null
17,158,153
null
Principle of the method.
null
24
5,137
0
false
null
null
Principle of the method.
true
true
true
true
true
854
6
INTRODUCTION
0
null
null
17,158,153
null
Diploid cells (a) are shown containing two haplotypes (upper-case, blue; and lower-case, yellow).
null
97
5,138
0
false
null
null
Diploid cells (a) are shown containing two haplotypes (upper-case, blue; and lower-case, yellow).
true
true
true
true
true
854
6
INTRODUCTION
0
null
null
17,158,153
null
DNA is prepared (b) with inevitable breakage through shearing, and dispensed at extreme dilution into aliquots (c), each containing much less than a complete genome.
null
165
5,139
0
false
null
null
DNA is prepared (b) with inevitable breakage through shearing, and dispensed at extreme dilution into aliquots (c), each containing much less than a complete genome.
true
true
true
true
true
854
6
INTRODUCTION
0
null
null
17,158,153
null
Initially, the samples are pre-screened by PCR to find out which loci they each contain, but without genotyping (d) red circles indicate a positive PCR result; red lines show the inferred extent of the fragments in each aliquot.
null
228
5,140
0
false
null
null
Initially, the samples are pre-screened by PCR to find out which loci they each contain, but without genotyping (d) red circles indicate a positive PCR result; red lines show the inferred extent of the fragments in each aliquot.
true
true
true
true
true
854
6
INTRODUCTION
0
null
null
17,158,153
null
Only a handful of aliquots then need to be genotyped for each locus (e).
null
72
5,141
0
false
null
null
Only a handful of aliquots then need to be genotyped for each locus (e).
true
true
true
true
true
854
6
INTRODUCTION
0
null
null
17,158,153
null
From these results, the complete haplotypes (f) can be reconstructed.
null
69
5,142
0
false
null
null
From these results, the complete haplotypes (f) can be reconstructed.
true
true
true
true
true
854
6
INTRODUCTION
0
null
null
17,158,153
null
Note that a few aliquots may contain mixed haplotypes.
null
54
5,143
0
false
null
null
Note that a few aliquots may contain mixed haplotypes.
true
true
true
true
true
854
6
INTRODUCTION
0
null
null
17,158,153
null
In this case, two of the aliquots give the partial haplotypes rs and RS, whilst the rightmost one gives the mixed haplotype rSβ€”the correct linkage phase is inferred from the majority (in this case, rs/RS rather than rS/Rs).
null
223
5,144
0
false
null
null
In this case, two of the aliquots give the partial haplotypes rs and RS, whilst the rightmost one gives the mixed haplotype rSβ€”the correct linkage phase is inferred from the majority (in this case, rs/RS rather than rS/Rs).
true
true
true
true
true
854
7
INTRODUCTION
0
null
null
17,158,153
null
The total number of genotypings required is comparable toβ€”or less thanβ€”that needed in pedigree studies.
null
103
5,145
0
false
null
null
The total number of genotypings required is comparable toβ€”or less thanβ€”that needed in pedigree studies.
true
true
true
true
true
855
7
INTRODUCTION
0
null
null
17,158,153
null
Moreover, the panel of aliquots can be re-accessed many times, allowing large-scale haplotyping.
null
96
5,146
0
false
null
null
Moreover, the panel of aliquots can be re-accessed many times, allowing large-scale haplotyping.
true
true
true
true
true
855
0
DISCUSSION
1
1
[ "b1", "b5", "b6", "b7", "b36", "b37" ]
17,158,153
pmid-10869235|pmid-15368617|NA|pmid-16479260|pmid-16909384|NA
Large-scale analyses have added greatly to our understanding of scope and significance of variation in the human genome.
[ "1", "5", "6", "7", "36", "37" ]
120
5,147
0
false
Large-scale analyses have added greatly to our understanding of scope and significance of variation in the human genome.
[]
Large-scale analyses have added greatly to our understanding of scope and significance of variation in the human genome.
true
true
true
true
true
856
0
DISCUSSION
1
1
[ "b1", "b5", "b6", "b7", "b36", "b37" ]
17,158,153
pmid-10869235|pmid-15368617|NA|pmid-16479260|pmid-16909384|NA
They have also drawn attention to the importance of haplotypes (the combination of alleles found on a single chromosome) as opposed to genotypes alone, in extracting useful information from this variation (1–5).
[ "1", "5", "6", "7", "36", "37" ]
211
5,148
0
false
They have also drawn attention to the importance of haplotypes (the combination of alleles found on a single chromosome) as opposed to genotypes alone, in extracting useful information from this variation.
[ "1–5" ]
They have also drawn attention to the importance of haplotypes (the combination of alleles found on a single chromosome) as opposed to genotypes alone, in extracting useful information from this variation.
true
true
true
true
true
856
0
DISCUSSION
1
7
[ "b1", "b5", "b6", "b7", "b36", "b37" ]
17,158,153
pmid-10869235|pmid-15368617|NA|pmid-16479260|pmid-16909384|NA
The utility of haplotypes inferred from population studies [such as the HapMap (6)] has recently been challenged (7).
[ "1", "5", "6", "7", "36", "37" ]
117
5,149
1
false
The utility of haplotypes inferred from population studies has recently been challenged.
[ "such as the HapMap (6)", "7" ]
The utility of haplotypes inferred from population studies has recently been challenged.
true
true
true
true
true
856
0
DISCUSSION
1
1
[ "b1", "b5", "b6", "b7", "b36", "b37" ]
17,158,153
pmid-10869235|pmid-15368617|NA|pmid-16479260|pmid-16909384|NA
In any case, it is more generally agreed that the prudent use of direct molecular haplotyping can add greatly to the power of association studies in identifying genes involved in complex diseases (36,37).
[ "1", "5", "6", "7", "36", "37" ]
204
5,150
0
false
In any case, it is more generally agreed that the prudent use of direct molecular haplotyping can add greatly to the power of association studies in identifying genes involved in complex diseases.
[ "36,37" ]
In any case, it is more generally agreed that the prudent use of direct molecular haplotyping can add greatly to the power of association studies in identifying genes involved in complex diseases.
true
true
true
true
true
856
0
DISCUSSION
1
1
[ "b1", "b5", "b6", "b7", "b36", "b37" ]
17,158,153
pmid-10869235|pmid-15368617|NA|pmid-16479260|pmid-16909384|NA
Against this, however, must be weighed the extra difficulty or cost of obtaining haplotype data: the easier haplotyping becomes, the greater the number of studies in which it becomes advantageous to use haplotype data.
[ "1", "5", "6", "7", "36", "37" ]
218
5,151
0
false
Against this, however, must be weighed the extra difficulty or cost of obtaining haplotype data: the easier haplotyping becomes, the greater the number of studies in which it becomes advantageous to use haplotype data.
[]
Against this, however, must be weighed the extra difficulty or cost of obtaining haplotype data: the easier haplotyping becomes, the greater the number of studies in which it becomes advantageous to use haplotype data.
true
true
true
true
true
856
1
DISCUSSION
0
null
null
17,158,153
pmid-10869235|pmid-15368617
We have demonstrated, for the first time, the accurate reconstruction of haplotypes spanning both large numbers of loci and long distances, using diploid DNA.
null
158
5,152
0
false
null
null
We have demonstrated, for the first time, the accurate reconstruction of haplotypes spanning both large numbers of loci and long distances, using diploid DNA.
true
true
true
true
true
857
1
DISCUSSION
0
null
null
17,158,153
pmid-10869235|pmid-15368617
The method is technically simple, requires no family members for pedigree analysis, and does not depend on assumptions of non-recombination, which are valid only over short distances.
null
183
5,153
0
false
null
null
The method is technically simple, requires no family members for pedigree analysis, and does not depend on assumptions of non-recombination, which are valid only over short distances.
true
true
true
true
true
857
1
DISCUSSION
0
null
null
17,158,153
pmid-10869235|pmid-15368617
The method is efficient, because each locus need be genotyped on only a handful of informative samples.
null
103
5,154
0
false
null
null
The method is efficient, because each locus need be genotyped on only a handful of informative samples.
true
true
true
true
true
857
1
DISCUSSION
0
null
null
17,158,153
pmid-10869235|pmid-15368617
In the present example, we reconstructed long haplotypes on chromosome 21 by genotyping only about seven samples per locus.
null
123
5,155
0
false
null
null
In the present example, we reconstructed long haplotypes on chromosome 21 by genotyping only about seven samples per locus.
true
true
true
true
true
857
1
DISCUSSION
0
null
null
17,158,153
pmid-10869235|pmid-15368617
Indeed, statistical analysis shows that strongly-supported haplotypes can be reconstructed with fewer genotypings than would be needed in conventional pedigree analysis.
null
169
5,156
0
false
null
null
Indeed, statistical analysis shows that strongly-supported haplotypes can be reconstructed with fewer genotypings than would be needed in conventional pedigree analysis.
true
true
true
true
true
857
2
DISCUSSION
1
38
[ "b38", "b33" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
Aside from the DNA concentration of the aliquots, the only factors which determine the statistical power of the method are the average size of the DNA fragments and the spacing between successive heterozygous loci along the chromosome.
[ "38", "33" ]
235
5,157
0
false
Aside from the DNA concentration of the aliquots, the only factors which determine the statistical power of the method are the average size of the DNA fragments and the spacing between successive heterozygous loci along the chromosome.
[]
Aside from the DNA concentration of the aliquots, the only factors which determine the statistical power of the method are the average size of the DNA fragments and the spacing between successive heterozygous loci along the chromosome.
true
true
true
true
true
858
2
DISCUSSION
1
38
[ "b38", "b33" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
Clearly, haplotypes cannot be reconstructed when none of the fragments is long enough to span the distance from one heterozygous locus to the next.
[ "38", "33" ]
147
5,158
0
false
Clearly, haplotypes cannot be reconstructed when none of the fragments is long enough to span the distance from one heterozygous locus to the next.
[]
Clearly, haplotypes cannot be reconstructed when none of the fragments is long enough to span the distance from one heterozygous locus to the next.
true
true
true
true
true
858
2
DISCUSSION
1
38
[ "b38", "b33" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
However, significant statistical power remains even when the distance between loci approaches the average fragment size (Table 1) since the occasional longer, informative fragments are identified in the initial pre-screening.
[ "38", "33" ]
225
5,159
0
false
However, significant statistical power remains even when the distance between loci approaches the average fragment size (Table 1) since the occasional longer, informative fragments are identified in the initial pre-screening.
[]
However, significant statistical power remains even when the distance between loci approaches the average fragment size (Table 1) since the occasional longer, informative fragments are identified in the initial pre-screening.
true
true
true
true
true
858
2
DISCUSSION
1
38
[ "b38", "b33" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
We were able to build haplotypes which spanned >160 kb between successive heterozygous loci (chromosome 21, loci rs222969–rs2187226).
[ "38", "33" ]
133
5,160
0
false
We were able to build haplotypes which spanned >160 kb between successive heterozygous loci (chromosome 21, loci rs222969–rs2187226).
[]
We were able to build haplotypes which spanned >160 kb between successive heterozygous loci.
true
true
true
true
true
858
2
DISCUSSION
1
38
[ "b38", "b33" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
Haplotype blocks in humans are rarely longer than this (38).
[ "38", "33" ]
60
5,161
1
false
Haplotype blocks in humans are rarely longer than this.
[ "38" ]
Haplotype blocks in humans are rarely longer than this.
true
true
true
true
true
858
2
DISCUSSION
1
33
[ "b38", "b33" ]
17,158,153
NA|pmid-16479260|pmid-15231751|pmid-9521877
If necessary, however, far longer DNA fragments can be isolated at extreme dilution directly from pulsed-field gels (33) and make it possible to reconstruct haplotypes between even more widely-spaced loci.
[ "38", "33" ]
205
5,162
1
false
If necessary, however, far longer DNA fragments can be isolated at extreme dilution directly from pulsed-field gels and make it possible to reconstruct haplotypes between even more widely-spaced loci.
[ "33" ]
If necessary, however, far longer DNA fragments can be isolated at extreme dilution directly from pulsed-field gels and make it possible to reconstruct haplotypes between even more widely-spaced loci.
true
true
true
true
true
858
3
DISCUSSION
0
null
null
17,158,153
pmid-10693791|pmid-16251461|pmid-2573038|pmid-15637233|pmid-12060700
In this paper, we have focused on the common problem of reconstructing the two haplotypes present in a diploid DNA sample.
null
122
5,163
0
false
null
null
In this paper, we have focused on the common problem of reconstructing the two haplotypes present in a diploid DNA sample.
true
true
true
true
true
859
3
DISCUSSION
0
null
null
17,158,153
pmid-10693791|pmid-16251461|pmid-2573038|pmid-15637233|pmid-12060700
However, there is no reason why the same approach cannot be applied to reconstruct multiple haplotypes from the mixed DNA of many individuals.
null
142
5,164
0
false
null
null
However, there is no reason why the same approach cannot be applied to reconstruct multiple haplotypes from the mixed DNA of many individuals.
true
true
true
true
true
859
4
DISCUSSION
1
39
[ "b39", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
On a technical level (and returning to the analysis of diploid samples), we note that the initial DNA dilution and PEP need be done only once.
[ "39", "32" ]
142
5,165
0
false
On a technical level (and returning to the analysis of diploid samples), we note that the initial DNA dilution and PEP need be done only once.
[]
On a technical level (and returning to the analysis of diploid samples), we note that the initial DNA dilution and PEP need be done only once.
true
true
true
true
true
860
4
DISCUSSION
1
39
[ "b39", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
This gives sufficient product for ∼30–50 multiplex pre-screening reactions, each of which can comprise many tens of markers [we have shown elsewhere (39) that several hundred loci can be multiplexed in this way and amplified from each fraction of the PEP].
[ "39", "32" ]
256
5,166
0
false
This gives sufficient product for ∼30–50 multiplex pre-screening reactions, each of which can comprise many tens of markers.
[ "we have shown elsewhere (39) that several hundred loci can be multiplexed in this way and amplified from each fraction of the PEP" ]
This gives sufficient product for ∼30–50 multiplex pre-screening reactions, each of which can comprise many tens of markers.
true
true
true
true
true
860
4
DISCUSSION
1
39
[ "b39", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
So a single initial sample prep is sufficient to haplotype many hundreds or several thousands of SNP loci.
[ "39", "32" ]
106
5,167
0
false
So a single initial sample prep is sufficient to haplotype many hundreds or several thousands of SNP loci.
[]
So a single initial sample prep is sufficient to haplotype many hundreds or several thousands of SNP loci.
true
true
true
true
true
860
4
DISCUSSION
1
39
[ "b39", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
In this respect, our method complements the β€˜polony’ approach of Zhang et al.
[ "39", "32" ]
77
5,168
0
false
In this respect, our method complements the β€˜polony’ approach of Zhang et al.
[]
In this respect, our method complements the β€˜polony’ approach of Zhang et al.
true
true
true
true
true
860
4
DISCUSSION
1
32
[ "b39", "b32" ]
17,158,153
pmid-3419517|pmid-7721277|pmid-1974719|pmid-15884673|pmid-12140338|pmid-16134125|pmid-16493423|pmid-15875012|pmid-16493423
(32), which they claim can be used to analyse large numbers of individuals, but only for modest numbers of SNPs.
[ "39", "32" ]
112
5,169
1
false
, which they claim can be used to analyse large numbers of individuals, but only for modest numbers of SNPs.
[ "32" ]
, which they claim can be used to analyse large numbers of individuals, but only for modest numbers of SNPs.
false
false
true
true
false
860
5
DISCUSSION
1
42
[ "b39", "b41", "b42", "b43" ]
17,158,153
pmid-15875012|NA|pmid-16362058|pmid-16721378
The dilution and multiplex amplification steps which we use are straightforward, and have been shown to be robust in other contexts inluding genome mapping (39–41), the analysis of ancient DNA (42) and the measurement of copy-number variation (43).
[ "39", "41", "42", "43" ]
248
5,170
1
false
The dilution and multiplex amplification steps which we use are straightforward, and have been shown to be robust in other contexts inluding genome mapping, the analysis of ancient DNA and the measurement of copy-number variation.
[ "39–41", "42", "43" ]
The dilution and multiplex amplification steps which we use are straightforward, and have been shown to be robust in other contexts inluding genome mapping, the analysis of ancient DNA and the measurement of copy-number variation.
true
true
true
true
true
861
5
DISCUSSION
1
39
[ "b39", "b41", "b42", "b43" ]
17,158,153
pmid-15875012|NA|pmid-16362058|pmid-16721378
Multiplexing the first phase of the hemi-nested PCR (in contrast to multiplexing conventional single-phase PCRs) is surprisingly easy and does not constrain primer design.
[ "39", "41", "42", "43" ]
171
5,171
0
false
Multiplexing the first phase of the hemi-nested PCR (in contrast to multiplexing conventional single-phase PCRs) is surprisingly easy and does not constrain primer design.
[]
Multiplexing the first phase of the hemi-nested PCR (in contrast to multiplexing conventional single-phase PCRs) is surprisingly easy and does not constrain primer design.
true
true
true
true
true
861
5
DISCUSSION
1
39
[ "b39", "b41", "b42", "b43" ]
17,158,153
pmid-15875012|NA|pmid-16362058|pmid-16721378
We have evaluated a wide range of alternative whole-genome amplification protocols (data not shown), but still find PEP to be the most representative and reproducible when starting from truly sub-genomic quantities of template.
[ "39", "41", "42", "43" ]
227
5,172
0
false
We have evaluated a wide range of alternative whole-genome amplification protocols (data not shown), but still find PEP to be the most representative and reproducible when starting from truly sub-genomic quantities of template.
[]
We have evaluated a wide range of alternative whole-genome amplification protocols (data not shown), but still find PEP to be the most representative and reproducible when starting from truly sub-genomic quantities of template.
true
true
true
true
true
861
5
DISCUSSION
1
39
[ "b39", "b41", "b42", "b43" ]
17,158,153
pmid-15875012|NA|pmid-16362058|pmid-16721378
Nevertheless, we continue to explore other techniques for the primary amplification step, which would ideally give both faithful representation of sub-genomic samples and, with a sufficient level of amplification, would permit the use of only a single-phase PCR afterwards.
[ "39", "41", "42", "43" ]
273
5,173
0
false
Nevertheless, we continue to explore other techniques for the primary amplification step, which would ideally give both faithful representation of sub-genomic samples and, with a sufficient level of amplification, would permit the use of only a single-phase PCR afterwards.
[]
Nevertheless, we continue to explore other techniques for the primary amplification step, which would ideally give both faithful representation of sub-genomic samples and, with a sufficient level of amplification, would permit the use of only a single-phase PCR afterwards.
true
true
true
true
true
861
6
DISCUSSION
0
null
null
17,158,153
null
In these experiments, the final genotyping step was done by sequencing, since this was the most convenient method for us in analyzing relatively small numbers of samples.
null
170
5,174
0
false
null
null
In these experiments, the final genotyping step was done by sequencing, since this was the most convenient method for us in analyzing relatively small numbers of samples.
true
true
true
true
true
862
6
DISCUSSION
0
null
null
17,158,153
null
However, the protocol gives conventional PCR products which should be amenable to genotyping by many (though not all) other available technologies, some suited to much higher throughput.
null
186
5,175
0
false
null
null
However, the protocol gives conventional PCR products which should be amenable to genotyping by many (though not all) other available technologies, some suited to much higher throughput.
true
true
true
true
true
862
6
DISCUSSION
0
null
null
17,158,153
null
Moreover, the PCR products of the initial pre-screening reactions can be β€˜cherry-picked’ and used directly in the genotyping reactions, avoiding the need to repeat PCRs.
null
169
5,176
0
false
null
null
Moreover, the PCR products of the initial pre-screening reactions can be β€˜cherry-picked’ and used directly in the genotyping reactions, avoiding the need to repeat PCRs.
true
true
true
true
true
862
7
DISCUSSION
0
null
null
17,158,153
null
Finally, we note that this method requires only very small amounts of genomic DNA: a 10th of a nanogram or less.
null
112
5,177
0
false
null
null
Finally, we note that this method requires only very small amounts of genomic DNA: a 10th of a nanogram or less.
true
true
true
true
true
863
7
DISCUSSION
0
null
null
17,158,153
null
This should make it possible (though we have not tested this) to recover haplotype data from very small samples, such as biopsies of tumours in which chromosomal rearrangements may produce haplotypes not found in the normal DNA of the individual.
null
246
5,178
0
false
null
null
This should make it possible (though we have not tested this) to recover haplotype data from very small samples, such as biopsies of tumours in which chromosomal rearrangements may produce haplotypes not found in the normal DNA of the individual.
true
true
true
true
true
863
0
INTRODUCTION
1
1–3
[ "B1 B2 B3", "B4 B5 B6 B7 B8", "B9", "B7", "B2", "B3" ]
17,485,480
pmid-21016866|pmid-13483636|pmid-9576955|NA|pmid-4128827|pmid-4213002|pmid-7884920|pmid-4100527|pmid-10769073|pmid-7884920|pmid-13483636|pmid-9576955|pmid-11842256|pmid-12124448|pmid-12642099|pmid-9875324|pmid-12740026|pmid-15827147|pmid-15582654|pmid-9617766|pmid-9875324|pmid-9617766|pmid-12740026|pmid-15827147|pmid-1...
Several medically important enveloped viruses that infect the respiratory tract, such as influenza (1–3), respiratory syncytial virus (RSV) (4–8), and parainfluenza (9) virus, form both spherical and filamentous virions at the surface of infected cells.
[ "1–3", "4–8", "9", "7", "2", "3" ]
253
5,179
1
false
Several medically important enveloped viruses that infect the respiratory tract, such as influenza, respiratory syncytial virus (RSV), and parainfluenza virus, form both spherical and filamentous virions at the surface of infected cells.
[ "1–3", "4–8", "9" ]
Several medically important enveloped viruses that infect the respiratory tract, such as influenza, respiratory syncytial virus (RSV), and parainfluenza virus, form both spherical and filamentous virions at the surface of infected cells.
true
true
true
true
true
864
0
INTRODUCTION
1
7
[ "B1 B2 B3", "B4 B5 B6 B7 B8", "B9", "B7", "B2", "B3" ]
17,485,480
pmid-21016866|pmid-13483636|pmid-9576955|NA|pmid-4128827|pmid-4213002|pmid-7884920|pmid-4100527|pmid-10769073|pmid-7884920|pmid-13483636|pmid-9576955|pmid-11842256|pmid-12124448|pmid-12642099|pmid-9875324|pmid-12740026|pmid-15827147|pmid-15582654|pmid-9617766|pmid-9875324|pmid-9617766|pmid-12740026|pmid-15827147|pmid-1...
This has been observed both in cell culture models with high passage, laboratory strains, and from virus isolated directly from nasopharyngeal secretions or observed in pathology samples (7).
[ "1–3", "4–8", "9", "7", "2", "3" ]
191
5,180
1
false
This has been observed both in cell culture models with high passage, laboratory strains, and from virus isolated directly from nasopharyngeal secretions or observed in pathology samples.
[ "7" ]
This has been observed both in cell culture models with high passage, laboratory strains, and from virus isolated directly from nasopharyngeal secretions or observed in pathology samples.
true
true
true
true
true
864
0
INTRODUCTION
1
2
[ "B1 B2 B3", "B4 B5 B6 B7 B8", "B9", "B7", "B2", "B3" ]
17,485,480
pmid-21016866|pmid-13483636|pmid-9576955|NA|pmid-4128827|pmid-4213002|pmid-7884920|pmid-4100527|pmid-10769073|pmid-7884920|pmid-13483636|pmid-9576955|pmid-11842256|pmid-12124448|pmid-12642099|pmid-9875324|pmid-12740026|pmid-15827147|pmid-15582654|pmid-9617766|pmid-9875324|pmid-9617766|pmid-12740026|pmid-15827147|pmid-1...
It has been shown that in influenza, filamentous virions have a higher specific infectivity (2), and it has been theorized that the filamentous virus morphology may be more effective for both infecting cells and evading the host immune responses, particularly in the respiratory tract (3).
[ "1–3", "4–8", "9", "7", "2", "3" ]
289
5,181
1
false
It has been shown that in influenza, filamentous virions have a higher specific infectivity, and it has been theorized that the filamentous virus morphology may be more effective for both infecting cells and evading the host immune responses, particularly in the respiratory tract.
[ "2", "3" ]
It has been shown that in influenza, filamentous virions have a higher specific infectivity, and it has been theorized that the filamentous virus morphology may be more effective for both infecting cells and evading the host immune responses, particularly in the respiratory tract.
true
true
true
true
true
864
1
INTRODUCTION
1
10
[ "B10" ]
17,485,480
pmid-3182934|pmid-10064612|pmid-17052171|pmid-14630951
One important question about the filamentous virion is: What are the mechanisms by which these virions bud from the plasma membrane of an infected cell?
[ "10" ]
152
5,182
0
false
One important question about the filamentous virion is: What are the mechanisms by which these virions bud from the plasma membrane of an infected cell?
[]
One important question about the filamentous virion is: What are the mechanisms by which these virions bud from the plasma membrane of an infected cell?
true
true
true
true
true
865
1
INTRODUCTION
1
10
[ "B10" ]
17,485,480
pmid-3182934|pmid-10064612|pmid-17052171|pmid-14630951
To answer this question, we chose as our model system the A2 strain of human respiratory syncytial virus (hRSV), grown in non-polarized Vero cells.
[ "10" ]
147
5,183
0
false
To answer this question, we chose as our model system the A2 strain of human respiratory syncytial virus (hRSV), grown in non-polarized Vero cells.
[]
To answer this question, we chose as our model system the A2 strain of human respiratory syncytial virus (hRSV), grown in non-polarized Vero cells.
true
true
true
true
true
865
1
INTRODUCTION
1
10
[ "B10" ]
17,485,480
pmid-3182934|pmid-10064612|pmid-17052171|pmid-14630951
Since many aspects of virion assembly and replication have been studied with RSV, this system is ideal for the study of filamentous virion egress.
[ "10" ]
146
5,184
0
false
Since many aspects of virion assembly and replication have been studied with RSV, this system is ideal for the study of filamentous virion egress.
[]
Since many aspects of virion assembly and replication have been studied with RSV, this system is ideal for the study of filamentous virion egress.
true
true
true
true
true
865
1
INTRODUCTION
1
10
[ "B10" ]
17,485,480
pmid-3182934|pmid-10064612|pmid-17052171|pmid-14630951
To image the live-cell dynamics of the genomic viral ribonucleoprotein (vRNP) of hRSV, a molecular beacon (MB)-fluorescent probe was designed to target specifically the vRNA.
[ "10" ]
174
5,185
0
false
To image the live-cell dynamics of the genomic viral ribonucleoprotein (vRNP) of hRSV, a molecular beacon (MB)-fluorescent probe was designed to target specifically the vRNA.
[]
To image the live-cell dynamics of the genomic viral ribonucleoprotein (vRNP) of hRSV, a molecular beacon (MB)-fluorescent probe was designed to target specifically the vRNA.
true
true
true
true
true
865
1
INTRODUCTION
1
10
[ "B10" ]
17,485,480
pmid-3182934|pmid-10064612|pmid-17052171|pmid-14630951
This allowed for direct observations of both the morphology and mechanics of the processes leading to viral egress within the cellular context.
[ "10" ]
143
5,186
0
false
This allowed for direct observations of both the morphology and mechanics of the processes leading to viral egress within the cellular context.
[]
This allowed for direct observations of both the morphology and mechanics of the processes leading to viral egress within the cellular context.
true
true
true
true
true
865
1
INTRODUCTION
1
10
[ "B10" ]
17,485,480
pmid-3182934|pmid-10064612|pmid-17052171|pmid-14630951
This approach has significant advantages over the DIC (differential interference contrast) method used in the previous dynamics study (10) of RSV, which lacked molecular specificity and the contrast needed to observe vertically oriented virions.
[ "10" ]
245
5,187
1
false
This approach has significant advantages over the DIC (differential interference contrast) method used in the previous dynamics study of RSV, which lacked molecular specificity and the contrast needed to observe vertically oriented virions.
[ "10" ]
This approach has significant advantages over the DIC (differential interference contrast) method used in the previous dynamics study of RSV, which lacked molecular specificity and the contrast needed to observe vertically oriented virions.
true
true
true
true
true
865
2
INTRODUCTION
1
11
[ "B11", "B12 B13 B14 B15 B16", "B17", "B18", "B19 B20 B21 B22", "B23" ]
17,485,480
pmid-9630890|pmid-15084672|pmid-15377515|pmid-14583593|pmid-15809226|pmid-15084673|pmid-16378971|pmid-15942027|pmid-7691830|pmid-9653126|pmid-16483318|pmid-15454466|pmid-15205532
Molecular beacons are dual-labeled, nucleic acid probes with a reporter fluorophore at one end and a quencher at the other.
[ "11", "12–16", "17", "18", "19–22", "23" ]
123
5,188
0
false
Molecular beacons are dual-labeled, nucleic acid probes with a reporter fluorophore at one end and a quencher at the other.
[]
Molecular beacons are dual-labeled, nucleic acid probes with a reporter fluorophore at one end and a quencher at the other.
true
true
true
true
true
866
2
INTRODUCTION
1
11
[ "B11", "B12 B13 B14 B15 B16", "B17", "B18", "B19 B20 B21 B22", "B23" ]
17,485,480
pmid-9630890|pmid-15084672|pmid-15377515|pmid-14583593|pmid-15809226|pmid-15084673|pmid-16378971|pmid-15942027|pmid-7691830|pmid-9653126|pmid-16483318|pmid-15454466|pmid-15205532
They are designed to form a stem-loop hairpin structure so that fluorescence emission occurs only when the probe hybridizes to a complementary target, resulting in a high signal-to-background ratio (SBR) (11).
[ "11", "12–16", "17", "18", "19–22", "23" ]
209
5,189
1
false
They are designed to form a stem-loop hairpin structure so that fluorescence emission occurs only when the probe hybridizes to a complementary target, resulting in a high signal-to-background ratio (SBR).
[ "11" ]
They are designed to form a stem-loop hairpin structure so that fluorescence emission occurs only when the probe hybridizes to a complementary target, resulting in a high signal-to-background ratio (SBR).
true
true
true
true
true
866
2
INTRODUCTION
1
12–16
[ "B11", "B12 B13 B14 B15 B16", "B17", "B18", "B19 B20 B21 B22", "B23" ]
17,485,480
pmid-9630890|pmid-15084672|pmid-15377515|pmid-14583593|pmid-15809226|pmid-15084673|pmid-16378971|pmid-15942027|pmid-7691830|pmid-9653126|pmid-16483318|pmid-15454466|pmid-15205532
Although MBs have been used in limited live-cell mRNA studies (12–16), their potential for the analysis of viral RNA in living cells has only recently been demonstrated (17,18).
[ "11", "12–16", "17", "18", "19–22", "23" ]
177
5,190
1
false
Although MBs have been used in limited live-cell mRNA studies, their potential for the analysis of viral RNA in living cells has only recently been demonstrated.
[ "12–16", "17,18" ]
Although MBs have been used in limited live-cell mRNA studies, their potential for the analysis of viral RNA in living cells has only recently been demonstrated.
true
true
true
true
true
866
2
INTRODUCTION
1
19–22
[ "B11", "B12 B13 B14 B15 B16", "B17", "B18", "B19 B20 B21 B22", "B23" ]
17,485,480
pmid-9630890|pmid-15084672|pmid-15377515|pmid-14583593|pmid-15809226|pmid-15084673|pmid-16378971|pmid-15942027|pmid-7691830|pmid-9653126|pmid-16483318|pmid-15454466|pmid-15205532
Other methods for imaging RNA in live cells, including the use of fluorescently labeled full-length RNAs or RNPs (19–22) and GFP-fused RNA-binding proteins (GFP-MS2) (23), do not allow for the evaluation of unmodified viral particles.
[ "11", "12–16", "17", "18", "19–22", "23" ]
234
5,191
1
false
Other methods for imaging RNA in live cells, including the use of fluorescently labeled full-length RNAs or RNPs and GFP-fused RNA-binding proteins (GFP-MS2), do not allow for the evaluation of unmodified viral particles.
[ "19–22", "23" ]
Other methods for imaging RNA in live cells, including the use of fluorescently labeled full-length RNAs or RNPs and GFP-fused RNA-binding proteins, do not allow for the evaluation of unmodified viral particles.
true
true
true
true
true
866
3
INTRODUCTION
1
24
[ "B24", "B25", "B24", "B25", "B26", "B27 B28 B29", "B28", "B12" ]
17,485,480
pmid-9671772|pmid-9037376|pmid-9671772|pmid-9037376|pmid-12771228|pmid-9547284|pmid-2726482|pmid-12669716|pmid-2726482|pmid-15084672
For the imaging experiments, a single chimeric MB, with a DNA backbone stem and 2β€²-O-Methyl RNA backbone hybridization domain, was designed to target a gene-end-intergenic-gene-start sequence, 3β€²-UUU UUA CCC CGU UUA U-5β€², that has three exact repeats (Figure 1A) (24,25).
[ "24", "25", "24", "25", "26", "27–29", "28", "12" ]
271
5,192
0
false
For the imaging experiments, a single chimeric MB, with a DNA backbone stem and 2β€²-O-Methyl RNA backbone hybridization domain, was designed to target a gene-end-intergenic-gene-start sequence, 3β€²-UUU UUA CCC CGU UUA U-5β€², that has three exact repeats (Figure 1A).
[ "24,25" ]
For the imaging experiments, a single chimeric MB, with a DNA backbone stem and 2β€²-O-Methyl RNA backbone hybridization domain, was designed to target a gene-end-intergenic-gene-start sequence, 3β€²-UUU UUA CCC CGU UUA U-5β€², that has three exact repeats (Figure 1A).
true
true
true
true
true
867
3
INTRODUCTION
1
24
[ "B24", "B25", "B24", "B25", "B26", "B27 B28 B29", "B28", "B12" ]
17,485,480
pmid-9671772|pmid-9037376|pmid-9671772|pmid-9037376|pmid-12771228|pmid-9547284|pmid-2726482|pmid-12669716|pmid-2726482|pmid-15084672
Successfully used in antisense experiments (24,25), this site was considered the most accessible and therefore a prime site for probe hybridization.
[ "24", "25", "24", "25", "26", "27–29", "28", "12" ]
148
5,193
0
false
Successfully used in antisense experiments, this site was considered the most accessible and therefore a prime site for probe hybridization.
[ "24,25" ]
Successfully used in antisense experiments, this site was considered the most accessible and therefore a prime site for probe hybridization.
true
true
true
true
true
867
3
INTRODUCTION
1
24
[ "B24", "B25", "B24", "B25", "B26", "B27 B28 B29", "B28", "B12" ]
17,485,480
pmid-9671772|pmid-9037376|pmid-9671772|pmid-9037376|pmid-12771228|pmid-9547284|pmid-2726482|pmid-12669716|pmid-2726482|pmid-15084672
Targeting the repeated sequence provided signal amplification, resulting in a significantly increased SBR.
[ "24", "25", "24", "25", "26", "27–29", "28", "12" ]
106
5,194
0
false
Targeting the repeated sequence provided signal amplification, resulting in a significantly increased SBR.
[]
Targeting the repeated sequence provided signal amplification, resulting in a significantly increased SBR.
true
true
true
true
true
867
3
INTRODUCTION
1
24
[ "B24", "B25", "B24", "B25", "B26", "B27 B28 B29", "B28", "B12" ]
17,485,480
pmid-9671772|pmid-9037376|pmid-9671772|pmid-9037376|pmid-12771228|pmid-9547284|pmid-2726482|pmid-12669716|pmid-2726482|pmid-15084672
In addition, since the target RNP is concentrated in cytoplasmic granules, often called inclusion bodies, and in viral filaments, which contain multiple copies of the vRNP, the signal was further enhanced.
[ "24", "25", "24", "25", "26", "27–29", "28", "12" ]
205
5,195
0
false
In addition, since the target RNP is concentrated in cytoplasmic granules, often called inclusion bodies, and in viral filaments, which contain multiple copies of the vRNP, the signal was further enhanced.
[]
In addition, since the target RNP is concentrated in cytoplasmic granules, often called inclusion bodies, and in viral filaments, which contain multiple copies of the vRNP, the signal was further enhanced.
true
true
true
true
true
867
3
INTRODUCTION
1
26
[ "B24", "B25", "B24", "B25", "B26", "B27 B28 B29", "B28", "B12" ]
17,485,480
pmid-9671772|pmid-9037376|pmid-9671772|pmid-9037376|pmid-12771228|pmid-9547284|pmid-2726482|pmid-12669716|pmid-2726482|pmid-15084672
A 2β€²-O-Methyl RNA/DNA chimera design was used for the MB primarily because of its generally higher SBR (26) when binding to RNA.
[ "24", "25", "24", "25", "26", "27–29", "28", "12" ]
128
5,196
1
false
A 2β€²-O-Methyl RNA/DNA chimera design was used for the MB primarily because of its generally higher SBR when binding to RNA.
[ "26" ]
A 2β€²-O-Methyl RNA/DNA chimera design was used for the MB primarily because of its generally higher SBR when binding to RNA.
true
true
true
true
true
867
3
INTRODUCTION
1
27–29
[ "B24", "B25", "B24", "B25", "B26", "B27 B28 B29", "B28", "B12" ]
17,485,480
pmid-9671772|pmid-9037376|pmid-9671772|pmid-9037376|pmid-12771228|pmid-9547284|pmid-2726482|pmid-12669716|pmid-2726482|pmid-15084672
This enhanced our ability to observe viral RNA being packaged into filamentous virion (SBR ranging from 11 to 30 using chimera versus less than 5 using DNA), and is likely due to 2β€²-O-Methyl RNAs higher affinity for RNA than DNA (27–29).
[ "24", "25", "24", "25", "26", "27–29", "28", "12" ]
237
5,197
1
false
This enhanced our ability to observe viral RNA being packaged into filamentous virion (SBR ranging from 11 to 30 using chimera versus less than 5 using DNA), and is likely due to 2β€²-O-Methyl RNAs higher affinity for RNA than DNA.
[ "27–29" ]
This enhanced our ability to observe viral RNA being packaged into filamentous virion (SBR ranging from 11 to 30 using chimera versus less than 5 using DNA), and is likely due to 2β€²-O-Methyl RNAs higher affinity for RNA than DNA.
true
true
true
true
true
867
3
INTRODUCTION
1
28
[ "B24", "B25", "B24", "B25", "B26", "B27 B28 B29", "B28", "B12" ]
17,485,480
pmid-9671772|pmid-9037376|pmid-9671772|pmid-9037376|pmid-12771228|pmid-9547284|pmid-2726482|pmid-12669716|pmid-2726482|pmid-15084672
The enhanced nuclease resistance is also a positive feature of using 2β€²-O-Methyl RNA for the hybridization domain (28), but we did not ever observe evidence of active probe degradation with DNA or chimera probes.
[ "24", "25", "24", "25", "26", "27–29", "28", "12" ]
212
5,198
1
false
The enhanced nuclease resistance is also a positive feature of using 2β€²-O-Methyl RNA for the hybridization domain, but we did not ever observe evidence of active probe degradation with DNA or chimera probes.
[ "28" ]
The enhanced nuclease resistance is also a positive feature of using 2β€²-O-Methyl RNA for the hybridization domain, but we did not ever observe evidence of active probe degradation with DNA or chimera probes.
true
true
true
true
true
867
3
INTRODUCTION
1
12
[ "B24", "B25", "B24", "B25", "B26", "B27 B28 B29", "B28", "B12" ]
17,485,480
pmid-9671772|pmid-9037376|pmid-9671772|pmid-9037376|pmid-12771228|pmid-9547284|pmid-2726482|pmid-12669716|pmid-2726482|pmid-15084672
The lack of probe degradation is likely due to the use of streptolysin O-based delivery, which avoids the endocytic pathway (12).
[ "24", "25", "24", "25", "26", "27–29", "28", "12" ]
129
5,199
1
false
The lack of probe degradation is likely due to the use of streptolysin O-based delivery, which avoids the endocytic pathway.
[ "12" ]
The lack of probe degradation is likely due to the use of streptolysin O-based delivery, which avoids the endocytic pathway.
true
true
true
true
true
867