File: NCBI_Variation.mod.dtd

package info (click to toggle)
python-biopython 1.68%2Bdfsg-3~bpo8%2B1
  • links: PTS, VCS
  • area: main
  • in suites: jessie-backports
  • size: 46,856 kB
  • sloc: python: 160,306; xml: 93,216; ansic: 9,118; sql: 1,208; makefile: 155; sh: 63
file content (944 lines) | stat: -rw-r--r-- 27,155 bytes parent folder | download | duplicates (7)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
<!-- ============================================
     ::DATATOOL:: Generated from "seqfeat.asn"
     ::DATATOOL:: by application DATATOOL version 2.3.1
     ::DATATOOL:: on 12/01/2011 23:05:19
     ============================================ -->

<!-- ============================================ -->
<!-- This section is mapped from module "NCBI-Variation"
================================================= -->

<!--
*** Variation-ref ***********************************************
*
*  Specification of variation features
*
-->

<!-- Elements used by other modules:
          Variation-ref,
          Variation-inst,
          VariantProperties,
          Population-data,
          Phenotype -->

<!-- Elements referenced from other modules:
          Int-fuzz,
          User-object,
          Object-id,
          Dbtag FROM NCBI-General,
          Seq-literal FROM NCBI-Sequence,
          SubSource FROM NCBI-BioSource,
          Seq-loc FROM NCBI-Seqloc,
          Pub FROM NCBI-Pub -->
<!-- ============================================ -->

<!--
 


















 Historically, the dbSNP definitions document data structures used in the
 processing and annotation of variations by the dbSNP group.  The intention
 is to provide information to clients that reflect internal information
 produced during the mapping of SNPs
 


















-->
<!ELEMENT VariantProperties (
        VariantProperties_version, 
        VariantProperties_resource-link?, 
        VariantProperties_gene-location?, 
        VariantProperties_effect?, 
        VariantProperties_mapping?, 
        VariantProperties_map-weight?, 
        VariantProperties_frequency-based-validation?, 
        VariantProperties_genotype?, 
        VariantProperties_project-data?, 
        VariantProperties_quality-check?, 
        VariantProperties_confidence?, 
        VariantProperties_other-validation?, 
        VariantProperties_allele-origin?, 
        VariantProperties_allele-state?, 
        VariantProperties_allele-frequency?, 
        VariantProperties_is-ancestral-allele?)>

<!ELEMENT VariantProperties_version (%INTEGER;)>
<!--
 NOTE:
 The format for most of these values is as an integer
 Unless otherwise noted, these integers represent a bitwise OR (= simple
 sum) of the possible values, and as such, these values represent the
 specific bit flags that may be set for each of the possible attributes
 here.
-->
<!ELEMENT VariantProperties_resource-link (%INTEGER;)>

<!--
    preserved	-  Clinical, Pubmed, Cited, (0x01)
    provisional	-  Provisional Third Party Annotations (0x02)
    has3D	-  Has 3D strcture SNP3D table (0x04)
    submitterLinkout	-  SNP->SubSNP->Batch link_out (0x08)
    clinical	-  Clinical if LSDB, OMIM, TPA, Diagnostic (0x10)
    genotypeKit	-  Marker exists on high density genotyping kit
         (0x20)
-->
<!ATTLIST VariantProperties_resource-link value (
        preserved |
        provisional |
        has3D |
        submitterLinkout |
        clinical |
        genotypeKit
        ) #IMPLIED >


<!ELEMENT VariantProperties_gene-location (%INTEGER;)>

<!--
    in-gene	-  Sequence intervals covered by a gene ID but not
         having an aligned transcript (0x01)
    near-gene-5	-  Within 2kb of the 5' end of a gene feature
    near-gene-3	-  Within 0.5kb of the 3' end of a gene feature
    intron	-  In Intron (0x08)
    donor	-  In donor splice-site (0x10)
    acceptor	-  In acceptor splice-site (0x20)
    utr-5	-  In 5' UTR (0x40)
    utr-3	-  In 3' UTR (0x80)
    in-start-codon	-  the variant is observed in a start codon
         (0x100)
    in-stop-codon	-  the variant is observed in a stop codon
         (0x200)
    intergenic	-  variant located between genes (0x400)
    conserved-noncoding	-  variant is located in a conserved
         non-coding region (0x800)
-->
<!ATTLIST VariantProperties_gene-location value (
        in-gene |
        near-gene-5 |
        near-gene-3 |
        intron |
        donor |
        acceptor |
        utr-5 |
        utr-3 |
        in-start-codon |
        in-stop-codon |
        intergenic |
        conserved-noncoding
        ) #IMPLIED >


<!ELEMENT VariantProperties_effect (%INTEGER;)>

<!--
    no-change	-  known to cause no functional changes
         since 0 does not combine with any other bit
         value, 'no-change' specifically implies that
         there are no consequences
    synonymous	-  one allele in the set does not change the encoded
         amino acid (0x1)
    nonsense	-  one allele in the set changes to STOP codon
         (TER).  (0x2)
    missense	-  one allele in the set changes protein peptide
         (0x4)
    frameshift	-  one allele in the set changes all downstream
         amino acids (0x8)
    up-regulator	-  the variant causes increased transcription
         (0x10)
    down-regulator	-  the variant causes decreased transcription
         (0x20)
    stop-gain	-  reference codon is not stop codon, but the snp
         variant allele changes the codon to a
         terminating codon.
    stop-loss	-  reverse of STOP-GAIN: reference codon is a
         stop codon, but a snp variant allele changes
         the codon to a non-terminating codon.
-->
<!ATTLIST VariantProperties_effect value (
        no-change |
        synonymous |
        nonsense |
        missense |
        frameshift |
        up-regulator |
        down-regulator |
        methylation |
        stop-gain |
        stop-loss
        ) #IMPLIED >


<!ELEMENT VariantProperties_mapping (%INTEGER;)>

<!--
    has-other-snp	-  Another SNP has the same mapped positions
         on reference assembly (0x01)
    has-assembly-conflict	-  Weight 1 or 2 SNPs that map to different
         chromosomes on different assemblies (0x02)
    is-assembly-specific	-  Only maps to 1 assembly (0x04)
-->
<!ATTLIST VariantProperties_mapping value (
        has-other-snp |
        has-assembly-conflict |
        is-assembly-specific
        ) #IMPLIED >

<!--
 map-weight captures specificity of placement
 NOTE: This is *NOT* a bitfield
-->
<!ELEMENT VariantProperties_map-weight (%INTEGER;)>
<!ATTLIST VariantProperties_map-weight value (
        is-uniquely-placed |
        placed-twice-on-same-chrom |
        placed-twice-on-diff-chrom |
        many-placements
        ) #IMPLIED >


<!ELEMENT VariantProperties_frequency-based-validation (%INTEGER;)>

<!--
    is-mutation	-  low frequency variation that is cited in
         journal or other reputable sources (0x01)
    above-5pct-all	-  >5% minor allele freq in each and all
         populations (0x02)
    above-5pct-1plus	-  >5% minor allele freq in 1+ populations (0x04)
    validated	-  Bit is set if the variant has a minor allele
         observed in two or more separate chromosomes
    above-1pct-all	-  >1% minor allele freq in each and all
         populations (0x10)
    above-1pct-1plus	-  >1% minor allele freq in 1+ populations (0x20)
-->
<!ATTLIST VariantProperties_frequency-based-validation value (
        is-mutation |
        above-5pct-all |
        above-5pct-1plus |
        validated |
        above-1pct-all |
        above-1pct-1plus
        ) #IMPLIED >


<!ELEMENT VariantProperties_genotype (%INTEGER;)>

<!--
    in-haplotype-set	-  Exists in a haplotype tagging set (0x01)
    has-genotypes	-  SNP has individual genotype (0x02)
-->
<!ATTLIST VariantProperties_genotype value (
        in-haplotype-set |
        has-genotypes
        ) #IMPLIED >


<!--
 project IDs are IDs from BioProjects
 in order to report information about project relationships, we
 require projects to be registered
 This field in many ways duplicates dbxrefs; however, the
 intention of this field is to more adequately reflect
 ownership and data source

 11/9/2010: DO NOT USE
 This field was changed in the spec in a breaking way; using it will
 break clients.  We are officially suppressing / abandoning this field.
 Clients who need to use this should instead place the data in
 Seq-feat.dbxref, using the db name 'BioProject'
-->
<!ELEMENT VariantProperties_project-data (VariantProperties_project-data_E*)>


<!ELEMENT VariantProperties_project-data_E (%INTEGER;)>

<!ELEMENT VariantProperties_quality-check (%INTEGER;)>

<!--
    contig-allele-missing	-  Reference sequence allele at the mapped
         position is not present in the SNP
         allele list, adjusted for orientation
         (0x01)
    withdrawn-by-submitter	-  One member SS is withdrawn by submitter
         (0x02)
    non-overlapping-alleles	-  RS set has 2+ alleles from different
         submissions and these sets share no
         alleles in common (0x04)
    strain-specific	-  Straing specific fixed difference (0x08)
    genotype-conflict	-  Has Genotype Conflict (0x10)
-->
<!ATTLIST VariantProperties_quality-check value (
        contig-allele-missing |
        withdrawn-by-submitter |
        non-overlapping-alleles |
        strain-specific |
        genotype-conflict
        ) #IMPLIED >


<!ELEMENT VariantProperties_confidence (%INTEGER;)>
<!ATTLIST VariantProperties_confidence value (
        unknown |
        likely-artifact |
        other
        ) #IMPLIED >


<!--
 has this variant been validated?
 While a boolean flag offers no subtle distinctions of validation
 methods, occasionally it is only known as a single boolean value
 NOTE: this flag is redundant and should be omitted if more comprehensive
 validation information is present
-->
<!ELEMENT VariantProperties_other-validation EMPTY>
<!ATTLIST VariantProperties_other-validation value ( true | false ) #REQUIRED >

<!--
 origin of this allele, if known
 note that these are powers-of-two, and represent bits; thus, we can
 represent more than one state simultaneously through a bitwise OR
-->
<!ELEMENT VariantProperties_allele-origin (%INTEGER;)>

<!--
    other	-  stopper - 2^31
-->
<!ATTLIST VariantProperties_allele-origin value (
        unknown |
        germline |
        somatic |
        inherited |
        paternal |
        maternal |
        de-novo |
        biparental |
        uniparental |
        not-tested |
        tested-inconclusive |
        not-reported |
        other
        ) #IMPLIED >

<!--
 observed allele state, if known
 NOTE: THIS IS NOT A BITFIELD!
-->
<!ELEMENT VariantProperties_allele-state (%INTEGER;)>
<!ATTLIST VariantProperties_allele-state value (
        unknown |
        homozygous |
        heterozygous |
        hemizygous |
        nullizygous |
        other
        ) #IMPLIED >


<!--
 NOTE:
 'allele-frequency' here refers to the minor allele frequency of the
 default population
-->
<!ELEMENT VariantProperties_allele-frequency (%REAL;)>

<!-- is this variant the ancestral allele? -->
<!ELEMENT VariantProperties_is-ancestral-allele EMPTY>
<!ATTLIST VariantProperties_is-ancestral-allele value ( true | false ) #REQUIRED >



<!ELEMENT Phenotype (
        Phenotype_source?, 
        Phenotype_term?, 
        Phenotype_xref?, 
        Phenotype_clinical-significance?)>

<!ELEMENT Phenotype_source (#PCDATA)>

<!ELEMENT Phenotype_term (#PCDATA)>

<!ELEMENT Phenotype_xref (Dbtag*)>
<!-- does this variant have known clinical significance? -->
<!ELEMENT Phenotype_clinical-significance (%INTEGER;)>
<!ATTLIST Phenotype_clinical-significance value (
        unknown |
        untested |
        non-pathogenic |
        probable-non-pathogenic |
        probable-pathogenic |
        pathogenic |
        drug-response |
        histocompatibility |
        other
        ) #IMPLIED >



<!ELEMENT Population-data (
        Population-data_population, 
        Population-data_genotype-frequency?, 
        Population-data_chromosomes-tested?, 
        Population-data_sample-ids?, 
        Population-data_allele-frequency?, 
        Population-data_flags?)>

<!-- assayed population (e.g. HAPMAP-CEU) -->
<!ELEMENT Population-data_population (#PCDATA)>

<!ELEMENT Population-data_genotype-frequency (%REAL;)>

<!ELEMENT Population-data_chromosomes-tested (%INTEGER;)>

<!ELEMENT Population-data_sample-ids (Object-id*)>

<!ELEMENT Population-data_allele-frequency (%REAL;)>
<!--
 This field is an explicit bit-field
 Valid values should be a bitwise combination (= simple sum)
 of any of the values below
-->
<!ELEMENT Population-data_flags (%INTEGER;)>
<!ATTLIST Population-data_flags value (
        is-default-population |
        is-minor-allele |
        is-rare-allele
        ) #IMPLIED >



<!ELEMENT Ext-loc (
        Ext-loc_id, 
        Ext-loc_location)>

<!ELEMENT Ext-loc_id (Object-id)>

<!ELEMENT Ext-loc_location (Seq-loc)>


<!ELEMENT Variation-ref (
        Variation-ref_id?, 
        Variation-ref_parent-id?, 
        Variation-ref_sample-id?, 
        Variation-ref_other-ids?, 
        Variation-ref_name?, 
        Variation-ref_synonyms?, 
        Variation-ref_description?, 
        Variation-ref_phenotype?, 
        Variation-ref_method?, 
        Variation-ref_population-data?, 
        Variation-ref_variant-prop?, 
        Variation-ref_validated?, 
        Variation-ref_clinical-test?, 
        Variation-ref_allele-origin?, 
        Variation-ref_allele-state?, 
        Variation-ref_allele-frequency?, 
        Variation-ref_is-ancestral-allele?, 
        Variation-ref_pub?, 
        Variation-ref_data, 
        Variation-ref_consequence?, 
        Variation-ref_location?, 
        Variation-ref_ext-locs?, 
        Variation-ref_ext?, 
        Variation-ref_somatic-origin?)>

<!--
 ids (i.e., SNP rsid / ssid, dbVar nsv/nssv)
 expected values include 'dbSNP|rs12334', 'dbSNP|ss12345', 'dbVar|nsv1'

 we relate three kinds of IDs here:
  - our current object's id
  - the id of this object's parent, if it exists
  - the sample ID that this item originates from
-->
<!ELEMENT Variation-ref_id (Dbtag)>

<!ELEMENT Variation-ref_parent-id (Dbtag)>

<!ELEMENT Variation-ref_sample-id (Object-id)>

<!ELEMENT Variation-ref_other-ids (Dbtag*)>

<!--
 names and synonyms
 some variants have well-known canonical names and possible accepted
 synonyms
-->
<!ELEMENT Variation-ref_name (#PCDATA)>

<!ELEMENT Variation-ref_synonyms (Variation-ref_synonyms_E*)>


<!ELEMENT Variation-ref_synonyms_E (#PCDATA)>

<!-- tag for comment and descriptions -->
<!ELEMENT Variation-ref_description (#PCDATA)>

<!-- phenotype -->
<!ELEMENT Variation-ref_phenotype (Phenotype*)>
<!-- sequencing / acuisition method -->
<!ELEMENT Variation-ref_method (Variation-ref_method_E*)>


<!ELEMENT Variation-ref_method_E (%INTEGER;)>
<!ATTLIST Variation-ref_method_E value (
        unknown |
        bac-acgh |
        computational |
        curated |
        digital-array |
        expression-array |
        fish |
        flanking-sequence |
        maph |
        mcd-analysis |
        mlpa |
        oea-assembly |
        oligo-acgh |
        paired-end |
        pcr |
        qpcr |
        read-depth |
        roma |
        rt-pcr |
        sage |
        sequence-alignment |
        sequencing |
        snp-array |
        snp-genoytyping |
        southern |
        western |
        optical-mapping |
        other
        ) #IMPLIED >


<!--
 Note about SNP representation and pretinent fields: allele-frequency,
 population, quality-codes:
 The case of multiple alleles for a SNP would be described by
 parent-feature of type Variation-set.diff-alleles, where the child
 features of type Variation-inst, all at the same location, would
 describe individual alleles.
 population data
 DEPRECATED - do not use
-->
<!ELEMENT Variation-ref_population-data (Population-data*)>

<!-- variant properties bit fields -->
<!ELEMENT Variation-ref_variant-prop (VariantProperties)>

<!--
 has this variant been validated?
 DEPRECATED: new field = VariantProperties.other-validation
-->
<!ELEMENT Variation-ref_validated EMPTY>
<!ATTLIST Variation-ref_validated value ( true | false ) #REQUIRED >


<!--
 link-outs to GeneTests database
 DEPRECATED - do not use
-->
<!ELEMENT Variation-ref_clinical-test (Dbtag*)>
<!--
 origin of this allele, if known
 note that these are powers-of-two, and represent bits; thus, we can
 represent more than one state simultaneously through a bitwise OR
 DEPRECATED: new field = VariantProperties.allele-origin
-->
<!ELEMENT Variation-ref_allele-origin (%INTEGER;)>

<!--
    other	-  stopper - 2^31
-->
<!ATTLIST Variation-ref_allele-origin value (
        unknown |
        germline |
        somatic |
        inherited |
        paternal |
        maternal |
        de-novo |
        biparental |
        uniparental |
        not-tested |
        tested-inconclusive |
        other
        ) #IMPLIED >

<!--
 observed allele state, if known
 DEPRECATED: new field = VariantProperties.allele-state
-->
<!ELEMENT Variation-ref_allele-state (%INTEGER;)>
<!ATTLIST Variation-ref_allele-state value (
        unknown |
        homozygous |
        heterozygous |
        hemizygous |
        nullizygous |
        other
        ) #IMPLIED >


<!--
 NOTE:
 'allele-frequency' here refers to the minor allele frequency of the
 default population
 DEPRECATED: new field = VariantProperties.allele-frequency
-->
<!ELEMENT Variation-ref_allele-frequency (%REAL;)>

<!--
 is this variant the ancestral allele?
 DEPRECATED: new field = VariantProperties.is-ancestral-allele
-->
<!ELEMENT Variation-ref_is-ancestral-allele EMPTY>
<!ATTLIST Variation-ref_is-ancestral-allele value ( true | false ) #REQUIRED >


<!--
 publication support.
 Note: made this pub instead of pub-equiv, since
 Pub can be pub-equiv and pub-equiv is a set of pubs, but it looks like
 Pub is more often used as top-level container
 DEPRECATED - do not use; use Seq-feat.dbxref instead
-->
<!ELEMENT Variation-ref_pub (Pub)>

<!ELEMENT Variation-ref_data (
        Variation-ref_data_unknown | 
        Variation-ref_data_note | 
        Variation-ref_data_uniparental-disomy | 
        Variation-ref_data_instance | 
        Variation-ref_data_set | 
        Variation-ref_data_complex)>

<!ELEMENT Variation-ref_data_unknown EMPTY>

<!--free-form -->
<!ELEMENT Variation-ref_data_note (#PCDATA)>

<!ELEMENT Variation-ref_data_uniparental-disomy EMPTY>

<!-- actual sequence-edit at feat.location -->
<!ELEMENT Variation-ref_data_instance (Variation-inst)>
<!--
 Set of related Variations.
 Location of the set equals to the union of member locations
-->
<!ELEMENT Variation-ref_data_set (
        Variation-ref_data_set_type, 
        Variation-ref_data_set_variations, 
        Variation-ref_data_set_name?)>

<!ELEMENT Variation-ref_data_set_type (%INTEGER;)>

<!--
    compound	-  complex change at the same location on the
         same molecule
    products	-  different products arising from the same
         variation in a precursor, e.g. r.[13g>a,
         13_88del]
    haplotype	-  changes on the same allele, e.g
         r.[13g>a;15u>c]
    genotype	-  changes on different alleles in the same
         genotype, e.g. g.[476C>T]+[476C>T]
    mosaic	-  different genotypes in the same individual
    individual	-  same organism; allele relationship unknown,
         e.g. g.[476C>T(+)183G>C]
    population	-  population
    alleles	-  set represents a set of observed alleles
    package	-  set represents a package of observations at
         a given location, generally containing
         asserted + reference
-->
<!ATTLIST Variation-ref_data_set_type value (
        unknown |
        compound |
        products |
        haplotype |
        genotype |
        mosaic |
        individual |
        population |
        alleles |
        package |
        other
        ) #IMPLIED >


<!ELEMENT Variation-ref_data_set_variations (Variation-ref*)>

<!ELEMENT Variation-ref_data_set_name (#PCDATA)>

<!--
 variant is a complex and undescribed change at the location
 This type of variant is known to occur in dbVar submissions
-->
<!ELEMENT Variation-ref_data_complex EMPTY>

<!ELEMENT Variation-ref_consequence (Variation-ref_consequence_E*)>


<!ELEMENT Variation-ref_consequence_E (
        Variation-ref_consequence_E_unknown | 
        Variation-ref_consequence_E_splicing | 
        Variation-ref_consequence_E_note | 
        Variation-ref_consequence_E_variation | 
        Variation-ref_consequence_E_frameshift | 
        Variation-ref_consequence_E_loss-of-heterozygosity)>

<!ELEMENT Variation-ref_consequence_E_unknown EMPTY>

<!--some effect on splicing -->
<!ELEMENT Variation-ref_consequence_E_splicing EMPTY>

<!--freeform -->
<!ELEMENT Variation-ref_consequence_E_note (#PCDATA)>

<!--
 Describe resulting variation in the product, e.g. missense,
 nonsense, silent, neutral, etc in a protein, that arises from
 THIS variation.
-->
<!ELEMENT Variation-ref_consequence_E_variation (Variation-ref)>
<!-- see http://www.hgvs.org/mutnomen/recs-prot.html -->
<!ELEMENT Variation-ref_consequence_E_frameshift (
        Variation-ref_consequence_E_frameshift_phase?, 
        Variation-ref_consequence_E_frameshift_x-length?)>

<!ELEMENT Variation-ref_consequence_E_frameshift_phase (%INTEGER;)>

<!ELEMENT Variation-ref_consequence_E_frameshift_x-length (%INTEGER;)>

<!ELEMENT Variation-ref_consequence_E_loss-of-heterozygosity (
        Variation-ref_consequence_E_loss-of-heterozygosity_reference?, 
        Variation-ref_consequence_E_loss-of-heterozygosity_test?)>

<!--
 In germline comparison, it will be reference genome assembly
 (default) or reference/normal population. In somatic mutation,
 it will be a name of the normal tissue.
-->
<!ELEMENT Variation-ref_consequence_E_loss-of-heterozygosity_reference (#PCDATA)>

<!-- Name of the testing subject type or the testing tissue. -->
<!ELEMENT Variation-ref_consequence_E_loss-of-heterozygosity_test (#PCDATA)>

<!--
 Observed location, if different from the parent set or feature.location.
 DEPRECATED - do not use
-->
<!ELEMENT Variation-ref_location (Seq-loc)>

<!--
 reference other locs, e.g. mapped source
 DEPRECATED - do not use
-->
<!ELEMENT Variation-ref_ext-locs (Ext-loc*)>

<!-- DEPRECATED - do not use; use Seq-feat.exts instead -->
<!ELEMENT Variation-ref_ext (User-object)>

<!ELEMENT Variation-ref_somatic-origin (Variation-ref_somatic-origin_E*)>


<!ELEMENT Variation-ref_somatic-origin_E (
        Variation-ref_somatic-origin_E_source?, 
        Variation-ref_somatic-origin_E_condition?)>

<!-- description of the somatic origin itself -->
<!ELEMENT Variation-ref_somatic-origin_E_source (SubSource)>
<!-- condition related to this origin's type -->
<!ELEMENT Variation-ref_somatic-origin_E_condition (
        Variation-ref_somatic-origin_E_condition_description?, 
        Variation-ref_somatic-origin_E_condition_object-id?)>

<!ELEMENT Variation-ref_somatic-origin_E_condition_description (#PCDATA)>

<!-- reference to BioTerm / other descriptive database -->
<!ELEMENT Variation-ref_somatic-origin_E_condition_object-id (Dbtag*)>


<!ELEMENT Delta-item (
        Delta-item_seq?, 
        Delta-item_multiplier?, 
        Delta-item_multiplier-fuzz?, 
        Delta-item_action?)>

<!ELEMENT Delta-item_seq (
        Delta-item_seq_literal | 
        Delta-item_seq_loc | 
        Delta-item_seq_this)>

<!ELEMENT Delta-item_seq_literal (Seq-literal)>

<!ELEMENT Delta-item_seq_loc (Seq-loc)>

<!--same location as variation-ref itself -->
<!ELEMENT Delta-item_seq_this EMPTY>

<!--
 Multiplier allows representing a tandem, e.g.  ATATAT as AT*3
 This allows describing CNV/SSR where delta=self  with a
 multiplier which specifies the count of the repeat unit.
assumed 1 if not specified.
-->
<!ELEMENT Delta-item_multiplier (%INTEGER;)>

<!ELEMENT Delta-item_multiplier-fuzz (Int-fuzz)>

<!ELEMENT Delta-item_action (%INTEGER;)>

<!--
    morph	-  replace len(seq) positions starting with location.start with seq
    offset	-  go downstream by distance specified by multiplier (upstream if < 0),
         in genomic context.
    del-at	-  excise sequence at location
         if multiplier is specified, delete len(location)*multiplier
         positions downstream
    ins-before	-  insert seq before the location.start
-->
<!ATTLIST Delta-item_action value (
        morph |
        offset |
        del-at |
        ins-before
        ) #IMPLIED >


<!-- Variation instance -->
<!ELEMENT Variation-inst (
        Variation-inst_type, 
        Variation-inst_delta, 
        Variation-inst_observation?)>

<!ELEMENT Variation-inst_type (%INTEGER;)>

<!--
    unknown	-  delta=[]
    identity	-  delta=[]
    inv	-  delta=[del, ins.seq=
         RevComp(variation-location)]
    snv	-  delta=[morph of length 1]
         NOTE: this is snV not snP; the latter
         requires frequency-based validation to be
         established in VariantProperties
         the strict definition of SNP is an SNV with
         an established population frequency of at
         least 1% in at least 1 popuplation
    mnp	-  delta=[morph of length >1]
    delins	-  delta=[del, ins]
    del	-  delta=[del]
    ins	-  delta=[ins]
    microsatellite	-  delta=[del, ins.seq= repeat-unit with fuzzy
         multiplier]
         variation-location is the microsat expansion
         on the sequence
    transposon	-  delta=[del, ins.seq= known donor or 'this']
         variation-location is equiv of transposon
         locs.
    cnv	-  delta=[del, ins= 'this' with fuzzy
         multiplier]
    direct-copy	-  delta=[ins.seq= upstream location on the
         same strand]
    rev-direct-copy	-  delta=[ins.seq= downstream location on the
         same strand]
    inverted-copy	-  delta=[ins.seq= upstream location on the
         opposite strand]
    everted-copy	-  delta=[ins.seq= downstream location on the
         opposite strand]
    translocation	-  delta=like delins
    prot-missense	-  delta=[morph of length 1]
    prot-nonsense	-  delta=[del]; variation-location is the tail
         of the protein being truncated
    prot-neutral	-  delta=[morph of length 1]
    prot-silent	-  delta=[morph of length 1, same AA as at
         variation-location]
    prot-other	-  delta=any
    other	-  delta=any
-->
<!ATTLIST Variation-inst_type value (
        unknown |
        identity |
        inv |
        snv |
        mnp |
        delins |
        del |
        ins |
        microsatellite |
        transposon |
        cnv |
        direct-copy |
        rev-direct-copy |
        inverted-copy |
        everted-copy |
        translocation |
        prot-missense |
        prot-nonsense |
        prot-neutral |
        prot-silent |
        prot-other |
        other
        ) #IMPLIED >


<!-- Sequence that replaces the location, in biological order. -->
<!ELEMENT Variation-inst_delta (Delta-item*)>
<!--
 'observation' is used to label items in a Variation-ref package
 This field is explicitly a bit-field, so the bitwise OR (= sum) of any
 of the values may be observed.
-->
<!ELEMENT Variation-inst_observation (%INTEGER;)>

<!--
    asserted	-  inst represents the asserted base at a
         position
    reference	-  inst represents the reference base at the
         position
    variant	-  inst represent the observed variant at a
         given position
-->
<!ATTLIST Variation-inst_observation value (
        asserted |
        reference |
        variant
        ) #IMPLIED >