Хромосомный микроматричный анализ. Клинические...
TRANSCRIPT
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CNVsCNPs
>20 . >9
(> 1 kb).
.
.
(>500 000).
.
FISH
MLPA
STR
SNPCNVCNP
.
(42 ) CNV
Ahn et al 2009 4773Altshuler_et_al_2010 5021Banerjee et al 2011 13Bentley_et_al_2008 6489708Campbell et al 2011 13Conrad et al 2006 935Conrad et al 2009 554Cooper et al 2008 368Cooper et al 2011 6183808De Smith et al 2007 4199Durbin_et_al_2010 2429452Forsberg_et_al_2012 39Hinds et al 2006 100Iafrate et al 2004 3471
Itsara et al 2009 19179Ju_et_al_2010 4Kidd et al 2008 1551Kidd et al 2010 8729Kidd et al 2010b 698Kim_et_al_2009 117Korbel et al 2007 1533Levy et al 2007 10079223Locke et al 2006 388McKernan_et_al_2009 2935611Mills et al 2006 5758512Pang_et_al_2010 237515Park_et_al_2010 21Perry et al 2008 2826Perry et al 2008b 29026Pinto et al 2007 7077Pinto_et_al_2011 1188Redon et al 2006 43Schuster et al 2010 187Shaikh et al 2009 7655Simon-Sanchez_et_al_2007 91Teague et al 2010 94Tuzun et al 2005 297Wang_et_al_2007 38Wang et al 2008 2720Wheeler et al 2008 23Wilson et al 2010 2696Young et al 2008 52
CN
V
DG
V
CNV
CNV (DGV)
0
2
4
6
8
10
12
14
16
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43
CNV
CNV (%
)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X
CNV
: 25582: 70: 256
:24 2013 .
(Mb)Cat-Eye Syndrome (Type I) 16.971p36 microdeletion syndrome 12.83Cri du Chat Syndrome (5p deletion) 12.5216p11.2-p12.2 microdeletion syndrome 8.692q33.1 deletion syndrome 8.28AZFb+AZFc 7.83AZFb 5.95Prader-Willi syndrome (Type 1) 5.69Angelman syndrome (Type 1) 5.69Prader-Willi Syndrome (Type 2) 4.82Angelman syndrome (Type 2) 4.82Xp11.22-p11.23 Microduplication 3.788p23.1 duplication syndrome 3.668p23.1 deletion syndrome 3.6612q14 microdeletion syndrome 3.57Smith-Magenis Syndrome 3.45Potocki-Lupski syndrome (17p11.2 duplication syndrome) 3.4515q26 overgrowth syndrome 3.16AZFc 3.06Miller-Dieker syndrome (MDS) 2.592p15-16.1 microdeletion syndrome 2.5322q11 duplication syndrome 2.4422q11 deletion syndrome (Velocardiofacial / DiGeorge syndrome) 2.44Potocki-Shaffer syndrome 2.0622q11.2 distal deletion syndrome 1.81Steroid sulphatase deficiency (STS) 1.683q29 microduplication syndrome 1.623q29 microdeletion syndrome 1.6215q24 recurrent microdeletion syndrome 1.5615q13.3 microdeletion syndrome 1.5416p13.11 recurrent microduplication (neurocognitive disorder susceptibility locus) 1.50
16p13.11 recurrent microdeletion (neurocognitive disorder susceptibility locus) 1.50
Williams-Beuren Syndrome (WBS) 1.40RCAD (renal cysts and diabetes) 1.40
(Mb)7q11.23 duplication syndrome 1.40Hereditary Liability to Pressure Palsies (HNPP) 1.37Charcot-Marie-Tooth syndrome type 1A (CMT1A) 1.371q21.1 recurrent microduplication (possible susceptibility locus for neurodevelopmental disorders) 1.35
1q21.1 recurrent microdeletion (susceptibility locus for neurodevelopmental disorders) 1.35
Sotos syndrome 1.33NF1-microdeletion syndrome 1.16AZFa 0.80ATR-16 syndrome 0.77WAGR 11p13 deletion syndrome 0.6517q21.31 recurrent microdeletion syndrome 0.5916p11.2 microduplication syndrome 0.59Wolf-Hirschhorn Syndrome 0.548q21.11 Microdeletion Syndrome 0.54Recurrent 16p12.1 microdeletion (neurodevelopmental susceptibility locus)
0.52
1q21.1 susceptibility locus for Thrombocytopenia-Absent Radius (TAR) syndrome
0.36
2q37 monosomy 0.35Leri-Weill dyschondrostosis (LWD) - SHOX deletion 0.29Early-onset Alzheimer disease with cerebral amyloid angiopathy 0.29Xp11.22-linked intellectual disability 0.2812p13.33 Microdeletion Syndrome 0.27Xq28 Microduplication 0.269q subtelomeric deletion syndrome 0.222p21 Microdeletion Syndrome 0.18Rubinstein-Taybi Syndrome 0.16Familial Adenomatous Polyposis 0.1422q13 deletion syndrome (Phelan-Mcdermid syndrome) 0.14Leri-Weill dyschondrostosis (LWD) - SHOX deletion 0.12Xq28 (MECP2) duplication 0.08Adult-onset autosomal dominant leukodystrophy (ADLD) 0.06Split hand/foot malformation 1 (SHFM1) 0.02Pelizaeus-Merzbacher disease 0.02
DECIPHER
Vissers et al. (2003) 20 ID, DF BAC Whole genome (1.0 Mb) 10.0%Shaw-Smith et al. (2004) 50 ID (moderate to severe) BAC Whole genome (1.0 Mb) 14.0%de Vries et al. (2005) 100 ID BAC Whole genome (50 kb) 10.0%Schoumans et al. (2005) 41 ID (mild to severe) BAC Whole genome (1.3 Mb) 9.8%Wong et al. (2005) 102 ID BAC Telomere 18.6%Ballif et al. (2006) 3600 ID, DD BAC Targeted 5.1%Friedman et al. (2006) 100 ID SNP (Affy 100k) Whole genome (30 kb) 11.0%Krepischi-Santos (2006) 95 ID, DF, MCA BAC Whole genome (1.0 Mb) 16.8%Menten et al. (2006) 140 ID, MCA BAC Whole genome (1.0 Mb) 13.6%Ming et al. (2006) 10 MCA SNP (Affy 100k) Whole genome (30 kb) 20.0%Miyake et al. (2006) 30 ID, MCA BAC Targeted (1.4 Mb) 16.7%Rosenberg et al. (2006) 81 ID (Mild to severe), DF BAC Whole genome (1.0 Mb) 16.0%Sharp et al. (2006) 290 ID +/- DF; +/- MCA BAC Targeted 5.5%Shaffer et al. (2006) 1500 Various indications BAC Targeted 5.6%Aradhya et al. I(2007) 20 ID or DD Agilent 44k Whole genome(70 kb) 35.0%Baris et al. (2007) 234 ID or DD, DF, MCA BAC Targeted 5.6%Engels et al. (2007) 60 ID BAC Whole genome (0.5 Mb) 10.0%Fan et al. (2007) 100 ID or DD (Agilent 44k) Whole genome (35 kb) 15.0%Hoyer et al. (2007) 104 ID SNP (Affy 100k) Whole genome (30 kb) 9.6%Lu et al. (2007) 2513 ID or DD, DF, MCA, ASD BAC Targeted 7.0%Newman et al. (2007) 36 DD, LD, DF BAC Whole genome (1.0 Mb) 13.8%Shaffer et al. (2007) 8789 ID or DD, MCA BAC Targeted 6.9%Shen et al. (2007) 211 ID or DD, MCA, MCA Oligo (Agilent) Targeted 7.6%Thuresson et al. (2007) 48 ID, DF, MCA BAC 1 Whole genome (1.0 Mb) 6.3%Wagenstaller (2007) 67 ID (mild tosevere) SNP (Affy 100k) Whole genome (30 kb) 16.4%Aston et al. (2008) 1075 ID, DD, DF, MCA BAC Whole genome (1.3 Mb) 5.3%Baldwin et al. (2008) 211 ID, DD, DF, MCA, ASD Agilent 44k Whole genome and Targeted 15.6%Pickering et al. (2008) 1176 ID or DD BAC Targeted and whole genome 7.8%Shevell et al. (2008) 94 ID, DD BAC Targeted 6.4%Xiang et al. (2008) 50 ID, DD Agilent 44k Whole genome (35 kb) 18.0%Lu et al. (2008) 638 MCA BAC and Oligo Targeted with backbone 17.1%
,
,
, .
, . . .
, .
,
500 (2012 - 2013 )
62%
5%
19%
2%
11%
500 (2012 -2013 )
500 (2012 -2013 )
0
50
100
150
200
250
300379
(76%)
106(21%)
CNV CNV c
15 (3%)
- 47XXY, 47XXX, 45X 568 (41/27)
22q11 ( ) (5)3q29 (2)7q11.23 ( ) (1)1q21 (1)5q35 ( ) (1)17q21.31 (1)16p11.2 (2)4p16.3 ( ) (1) 8q21.11 (1)9q (1)22q13 (Phelan-Mcdermid syndrome) (1)17p13.3 ( )) (1)8p23.1 (2)1p36 (1)1p32-1p31 (1)15q11.2 ( ) (1)
23
(1)(1)
PARK2 (1) (1)
(1) (1)
6
31?
500 (2012 -2013 )NV 106
.
X ( )
., , 2 . ?
: arr 3 12.1 12.2 12.3 13 14.1 (67146972-84157105) 1
: 16 490 890 .
. , 11 .:
:2q32.3q34q35q33.1q33.3q36.1q36.3q33.2, q36.2, q32.3 (197061843-229368433) 3
: 32 000 000 .
., , 24 . (34-5): ( )
: arr[hg19] 1q21.1q21.2(146,105,170-147,844,758)x11q21.1 .
., 2 .:
: arr[hg19] 15q11.2q13.1(23,615,768-28,644,578)x1
., , 10 . (31-8):
: arr[hg19] 7q11.23(72,718,277-74,175,429)x1
., , 2 . 4 . : , ,
:arr[hg19] 22q11.21(18,644,790-21,465,659)x1
, ,3 . 11 : , , .
: arr[hg19] 22q11.21(18,970,561-21,915,509)x322q11 .
., , 2,5 . . arr4p16.3(0-8731855) 1, 8p23.1(0-6999114) 3
4 8731855 .
., , 2,5 . . arr4p16.3(0-8731855) 1, 8p23.1(0-6999114) 3
4 8731855 .
., , 2,5 . . 4p16.3(0-8731855) 1, 8p23.1(0-6999114) 3
4 8731855 . 8 6999114 .
46,XY
)
., , 2,5 . . 4p16.3(0-8731855) 1, 8p23.1(0-6999114) 3
4 8731855 . 8 6999114 .
(FISH )
., , 5 .: , .
: arr[hg19] 11q24.3q25(128,976,457-134,938,470)x1arr[hg19] 16p13.3p13.13(85,880-10,632,149)x3
., , 5 .: , .
: arr[hg19] 11q24.3q25(128,976,457-134,938,470)x1arr[hg19] 16p13.3p13.13(85,880-10,632,149)x3
11 16 ( )
11
11 ,
16.
16
(FISH )
. , , 5 .: , .
: arr[hg19] 11q24.3q25(128,976,457-134,938,470)x1arr[hg19] 16p13.3p13.13(85,880-10,632,149)x3
., , 2 .:
: arr5q35.2q32.3 (175438045-177436413) 1 1 998 369 . ( , NSD1)
: , 1 . 9 . : , , .
:46,XX.arr2q13(110492576 -111365996) 1
: 347420 . ( NPHP1).
., , 4 9 .: , , , .
: arrXp11.4(39707242-39830900) 1 ( BCORC) 120 000 .
Xp11.4
., , 5 (46-2): ,
: arr[hg19] 4p16.3(68,345-2,730,573)x1
., 6,5 .: , ,
: arr8p23.1(8,207,297-9,533,138)x1
8p23.1
., , 1 4 . (50-4):
: arr[hg19] 9q34.3(139,455,126-141,020,389)x19q
., 6 4 . (38-4): .
:arr[hg19] 16p11.2(29,567,295-30,177,240)x116p11.2
1q21.1 Dup 8.0 (3.5 - 18.4) , ,
2p16.3 NRXN1 Del High for exonic , ,
,
deletions
3q29 VIPR2 Del 30.0 (1.9 - 480.4) ,
,
7q11.23 Dup 30.7 (3.4 - 275.1)
15q11.2-13.1 Dup 42.6(15.7 - 115.5) , ,
15q13.3 CHRNA7 Del 10.8(3.5 - 33.1) ,
16p11.2 Dup 11.8 (6.1 - 22.7) ,
16p11.2 Del 9.5 (5.2 - 17.4),
,
22q11.2 Dup 3.3 (1.6 - 6.6) ,
22q11.2 Del ,
CNVs (ASD)
OUT Psychiatry Rep (2013) 15:334 DOI 10.1007/s11920-012-0334-3 GENETIC DISORDERS (JF CUBELLS AND EB BINDER, SECTION EDITORS)The Genetics of Autism Spectrum Disorders - A Guide for CliniciansKarsten M. Heil • Christian P. Schaaf
Autism Genetics Collaborative (AGC)
Autism Genetics Resource Exchange (AGRE)
Collaborative Programs of Excellence in Autism (CPEA)
International Molecular Genetic Study of Autism Consortium (IMGSAC)
Autism Speaks, CIHR, CAN, Genome Canada, HHMI, Hospital for Sick Children Foundation, INSERM, MRC, NICHD, NIDCD, NIMH, NINDS, NLM Family Foundation, Swedish National Medical Council, Wellcome Trust, EU
Autism Genome Project (AGP)
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., , 1 . 1 .: : 46, XX,del(2)(q23?;q31?)
2 .: arr(1-22,X)x2
2
., , 1 . 1 .: : 46, XX,del(2)(q23?;q31?)
2 .: arr(1-22,X)x2 -
., , 1 . 1 .: : 46, XX,del(2)(q23?;q31?)
2 .: arr(1-22,X)x2
2
2 10
FISH )
(>3 . )
( ,
)
–
( )
1
2
., , 4 ..
: 46XY.arr22q12.3(34206143-34242538) 1,1 (245960375-249198692)x2 hmz,2(69043680-89129064) 2 hmz,2(95341387-109635905) 2 hmz,3(167079379-192209682) 2 hmz, 6(184718-8291827) 2hmz, 6(138484928-152432317) 2hmz, 8(130353226-146292734) 2hmz,11(128783745-134942626) 2hmz,
12(127432139-133004638) 2 hmz,16(31882909-35220544) 2 hmz, 22(47539975-51177928) 2hmz,22(16877134-25887513) 2hmz
(>5%)
-
= =>
( )
..
.> 10 .
.
, .
: – 6,11, 14, 15, 20
– 7, 14, 15,16.
., 1 . 1 . (
).:
arr[hg19] 16q22.2q24.3(72,785,592-90,163,275) hmz (17 .)arr[hg19] 16p13.3p13.2(89,560-9,775,196) hmz (9 .)
:
( )
, , . .
.
:
. ( .
..
.
., , 37 11 .
.
., , 32 12-13 .
1:82
., , 32 12-13 .
1:82,20. .
., , 36 12-13 .
> 7, .: arr[hg19] 10p12.2p12.1(22,653,798-28,400,604)x1
10. 5 746 806 .
., , 26 12 .
1:50,: arr22q13.31q13.33(48,032,444-51,197,725)x1
22 3 165 281 .
22
(FISH « »)
., , 26 12 .
1:50,: arr22q13.31q13.33(48,032,444-51,197,725)x1
22 3 165 281 .
., , 26 12 .
1:50,arr7q22.1q36.3(100622056-159119707)x2-3, 36%
58 497 651 .
):
arr11q24.3, q24.2, q25, q24.1(123094914-134938470)x1arr11q13.3, q13.4, q14.2, q14.3, q21, q22.1(69874016-122649035)x3
., , 26 10-11 .
Turner syndrome, 45,X
., , 37 .
Patau syndrome 47,XY,+13
24 (100%)
17 (71)
1
20 ( ) 1
10p12.2p12.1(22,653,798-28,400,604)x1 1
7q22.1q36.3(100,622,056-159,119,707)x2-322q13.31q13.33(48,032,444-51,197,725)x1 1arr11q24.3, q24.2, q25, q24.1(123094914-134938470)x1arr11q13.3, q13.4, q14.2, q14.3, q21, q22.1(69874016-122649035)x3
1
Turner syndrome, 45,X 1
Patau syndrome 47,XY,+13 1
7 (29%)
CMA Karyotype MLPA QF-PCR
173 23 (13.3) 22 (96) 16 (69) 12 (52) 14 (61)
235 12 (5.5) 12 (100) 11 (92) 12 (100) 11 (92)
145 8 (5.5) 8 (100) 5 (62) 5 (62) 1 (12)
273 11 (4.0) 11 (100) 8 (73) 7 (64) 6 (55)
20 2 (10.0) 2 (100) 2 (100) 2 (100) 2 (100)
60 1 (1.7) 1 (100) 0 (0) 1 (100) 0 (0)
906 57 56 (98) 42 (74) 39 (68) 34 (60)
6.3% 6.2% 4.6% 4.3% 3.6%
Hum Genet (2012) 131:513-523 DOI 10.1007/s00439-011-1095-5ORIGINAL INVESTIGATION
Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis
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