NimbleGen CGX Cytogenetics Solution

Translating Data into Meaning

Roche NimbleGen and Signature Genomic Laboratories

Expertise you can depend on

As a leading provider of genetic research tools, Roche NimbleGen provides a comprehensive suite of microarray solutions that help researchers to unravel and understand the structure and make-up of the genome. Through partnership with Signature Genomics, who pioneered the genotype-first approach to cytogenetics, Roche NimbleGen has developed a suite of NimbleGen CGX Cytogenetics arrays with a comprehensive workflow solution that delivers a new standard for molecular cytogenetic analysis. As a leader in the cytogenetics industry, Signature Genomics has established many of the methodologies that are now the standard for microarray analysis. In 2004, the company became the first to provide commercially viable microarray testing and analysis to the research services market. As a leader in array-based Comparative Genomic Hybridization (array CGH) for analysis of chromosomal abnormalities, Signature provides its clients with the expertise to understand and interpret complex genomic research studies. The combination of NimbleGen CGX Cytogenetics array workflow and Signature Genomics experience, knowledge, service and support in handling over 40,000 samples to date offers an integrated and complete solution for cytogenetic analysis. Together, we provide you with real and meaningful answers in your research. Additionally, the results of these studies have been incorporated into a proprietary database from Signature Genomics, Genoglyphix. It allows researchers secure online access from around the world to analyze and understand the meaning of genetic alteration and its impact on disease.

As one of the pioneers in the field of molecular cytogenetic analysis, we continuously work toward innovation and development of cutting-edge technologies to improve human health. Through partnership with Roche and use of the NimbleGen microarray technology, we aim to share our experience and expertise with the global cytogenetics community and significantly advance the field of cytogenetics. Lisa Shaffer President and CEO Signature Genomic Laboratories

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For life science research only. Not for use in diagnostic procedures.

Discover More with CGX Cytogenetics Arrays

Roche NimbleGen has developed CGX Cytogenetics arrays with the design from Signature Genomics to take advantage of array CGH methods. NimbleGen CGX Cytogenetics arrays offer a single proven design across array formats, one complete workflow solution, and scalability, all from a company known for life science innovation.

NimbleGen CGX Cytogenetics arrays offer multiple advantages for your high resolution chromosomal analysis needs over conventional methods: Higher resolution for more sensitive detection of small aberrations Easily scalable with high potential for automation Simple, fast, and less labor intensive workflow

One Proven Design

Roche Technical Support

A single proven cytogenetic design; designed by cytogeneticists for cytogeneticists

The support your research requires, from a company committed to supporting and advancing cytogenetics

One Complete Solution

From sample prep to data analysis, the complete cytogenetic workflow solution

Multiple array formats with a single design provide scalability for your analysis needs

Scalability

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Discover the Roche NimbleGen Difference:

NimbleGen CGX Arrays

Time: Order a catalog array with delivery in a matter of days

Sample Preparation and Labeling

Time: 5 hours (2 - 3 hours hands on)

Based on analysis of over 40,000 cytogenetic samples, NimbleGen CGX Cytogenetic arrays comprehensively cover cytogenetically relevant regions: Over 200 cytogenetic disease-associated regions More than 675 functionally significant genes Comprehensive, high resolution coverage of telomeric and pericentromeric regions Full coverage of pseudoautosomal regions Complete whole-genome backbone coverage Same design in all three array formats (CGX-3, CGX-6, CGX-12) provides scalability across platforms while minimizing validation requirements

Label your unfragmented DNA samples with the NimbleGen Dual-Color DNA Labeling Kit to ensure high-quality and accurate data: Functionally validated components provide consistent yields and labeling efficiency for maximum accuracy CGX-6 and CGX-12 arrays contain positive control probes for monitoring workflow success

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Cytogenetics Workflow Solution Ensures Optimal Research Results

Hybridization
Time: ~40 hours (<2 hours hands on)

Scanning
Time: 20 minutes per slide at 2m resolution (<5 - 20 minutes hands on)

Data Extraction and Analysis

Time: 20 - 60 minutes per sample

Hybridize in a NimbleGen Hybridization System for reliable and reproducible data. Robust hybridization systems allow you to focus on your experiment: Active mixing promotes uniform hybridization across the array Scalable system allows for batches of up to 144 samples to meet your experimental throughput needs

Scan at high resolution with the NimbleGen MS 200 Microarray Scanner: Maximum throughput of up to 576 samples (on CGX12 array) with the 48-slide autoloader Ozone mitigation system helps reduce signal degradation of dyes on arrays Advanced autofocus and autogain help provide consistent, optimal results

Extract and analyze array data with NimbleScan and Genoglyphix Software: Extract raw array with NimbleScan Software Generate Experimental Metrics Report to assess quality of microarray data Perform quality control and in-depth analysis with Genoglyphix Software

Contact Roche Microarray Technical Support: www.nimblegen.com/arraysupport

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Genoglyphix: Turning 40,000 Samples into Meaning;

A powerful data visualization software and database based on the analysis of over 40,000 cytogenetic samples (and still growing), Genoglyphix turns complexity into meaning. Designed and used by cytogeneticists, Genoglyphix offers a proven analysis

solution with an intuitive and complete workflow including sample tracking, alteration categorization and summary features, data management, data sharing with other Genoglyphix users and much, much more.

t Graphical representation of aberration

t Identify BAC clones t Genes aligned by genomic coordinates with links to OMIM, PubMed, and the UCSC databases t Database of Genomic Variants

t Signature Genomics database of over 10,000 aberrations

t Track your own samples in MyGCAD

t Genes listed in the RefSeq Database

p Figure 1: Data visualization in Genoglyphix.

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Designed by Cytogeneticists, for Cytogeneticists

Genoglyphix sets a new standard for arraybased cytogenetics analysis. Developed by Signature Genomics and available for exclusive use with NimbleGen CGX arrays, Genoglyphix genome browser software provides intuitive data visualization and annotation features for streamlined and rapid analysis of CGX data.

Genoglyphix Bringing multiple genetic databases into one tool

A database of over 10,000 genetic alterations identified in over 40,000 samples Links to the Database of Genomic Variants Known Genes compiled with information from databases such as OMIM, PubMed, UCSC, DGV, Ensembl Secure web-based (128-bit encryption) access to Genoglyphix database and software
p Figure 2: Various chromosomes shown in Genoglyphix. Example CGX-3 data shown in Genoglyphix Software. Top track: A 26.2 Mb deletion on chromosome 5p. Middle track: A 6.3 Mb deletion on chromosome 10q. Bottom track: A 9.1 Mb duplication on chromosome 8p.

Genoglyphix easily guides cytogeneticists through analysis with convenient tools such as:
Generate user-defined databases with MyGCAD and add custom tracks such as abnormal results, copy number variants, and analysis notes User-definable reporting features Easy-to-use workflow: sample tracking, alteration categorization, summary features, and data management. Optional sharing of data with other Genoglyphix users

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Same Proven Design Across CGX Arrays...

The NimbleGen Cytogenetics CGX arrays offer highresolution coverage of the entire human genome, with a subset of probes specifically targeted to disease associated regions including microdeletion/duplication, subtelomeric and pericentromeric regions. Combined with the reagents, instruments, and analysis software, these arrays provide a complete solution for your cytogenetic experiments. The data shown here demonstrates the high sensitivity and reproducibility achieved with all three array formats using representative research samples. Deletions and amplifications are reproducibly detected across array formats (Figure 3). Additionally, the high sensitivity of the CGX arrays allows detection of aberrations down to 20% mosaicism (Figure 4). The same array content and design across all three platforms provides the flexibility to quickly and easily scale your research from 3 to 6 to 12 samples per slide based on your sample throughput needs. To ensure consistently high data quality, the CGX arrays contain positive control probes for monitoring workflow success. When used with the NimbleGen Labeling and Hybridization Control Kit, the control probes ensures consistency in your workflow and reliability of your results.

p Figure 3: Reproducible detection of a deletion with NimbleGen CGX arrays. (Example CGX data shown in Genoglyphix Software.) The 16 Mb deletion (shown in blue boxes) is accurately detected on all CGX arrays, providing a scalable solution depending on required sample throughput. As each array format contains the same design, CGX analysis is identical for all arrays.

p Figure 4: Example CGX-12 data shown in Genoglyphix Software. A simulated mosaic titration series of a trisomy 21 sample was analyzed with CGX-12 arrays. The mosaic aberration is detected down to the 20% level (shown in magenta boxes).

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From the Complete Cytogenetics Solution

The CGX arrays offer significant advantages over conventional methods, such as karyotype and FISH, for analysis of chromosomal copy number changes. Our CGX arrays provide genome-wide analysis in a single assay at a resolution not achievable by previous methods, and has enabled the discovery of novel microdeletion and microduplication syndromes previously unrecognized using lower-resolution technologies.
Advantages of CGX Cytogenetics Arrays

In addition, when compared with traditional methods, CGX arrays are easier to use, require less time, and are amenable to automation. For these reasons, CGX arrays have rapidly emerged as a method of choice for molecular cytogenetic analysis of chromosomal abnormalities underpinning human diseases such as constitutional or developmental disorders.

Conventional Methods
Increased Detection Rate Resolution Protocol Turnaround Time Scalability

CGX Arrays 20% Tunable; less than 50 Kb in targeted regions Easy-to-use, less time and less labor intensive direct labeling of genomic DNA 3 - 4 days (dependent on array format and lab workflow) Scalable across all three array platforms; high potential for automation

4% 5 10 Mb Labor intensive; requires cell culture 4 10 days Not easily scalable or automated

Ordering Information
NimbleGen Arrays NimbleGen CGX-3 Array Cat. No. 05 986 834 001 05 947 987 001 NimbleGen CGX-6 Array 05 986 885 001 05 948 193 001 NimbleGen CGX-12 Array 05 986 869 001 05 947 995 001 05 948 002 001 Pack Size 2 slides 4 slides 1 slide 4 slides 1 slide 2 slides 4 slides

Instruments
NimbleGen Hybridization System 4 (110V) NimbleGen Hybridization System 12 (110V) NimbleGen Hybridization System 4 (220V) NimbleGen Hybridization System 12 (220V) NimbleGen Microarray Dryer (110V) NimbleGen Microarray Dryer (220V) NimbleGen MS 200 Microarray Scanner

Cat. No. 05 223 652 001 05 223 679 001 05 223 687 001 05 223 695 001 05 223 636 001 05 223 644 001 05 394 341 001

Reagents
NimbleGen Labeling and Hybridization Control Kit NimbleGen Dual-Color DNA Labeling Kit NimbleGen Hybridization Kit NimbleGen Hybridization Kit, LS NimbleGen Wash Buffer Kit NimbleGen Array Processing Accessories NimbleGen Sample Tracking Control Kit

Cat. No. 05 993 776 001 05 223 547 001 05 583 683 001 05 583 934 001 05 584 507 001 05 223 539 001 05 223 512 001

Software
NimbleScan Software Individual License NimbleScan Software Site License SignalMap Software Individual License Genoglyphix Software Site License Genoglyphix Software Site License Renewal

Cat. No. 05 933 315 001 05 933 331 001 05 225 051 001 05 852 307 001 05 852 323 001

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Targeted Regions Bilateral frontoparietal polymicrogyria (BFPP)

OMIM Locus 606854 GPR56

Band(s) 16q13 3q22.3 5q35.2 8q13.3 12q14.3 17q24.3 22q11.1 9p24.2 7q21.2 7p13 3q26.1 8q12.2 Xq21.2 6p12.3 11q13.3 15q26.1, 15q26.2 8p23.1 5p13.2 10q23.31 Xq13.1 5p15.2 7q36.3 3q24 22q11.21 10p14 Xp21.2 21q22.13 5q22.2 3q21.1 2p24.3 Xq22.3 Xq27.3 Xp11.23 1q41 2q24.3 16q13 Xp21.2 7p14.1 Xq28 Xq27.1 12q13.13 21q22.3 2p21 7q36.3 18p11.31 13q32.3 2q37.1-q37.3 9q22.32 14q13.1-q13.2 5q35.1 12q24.21 10p14 2p21 11p15.1 7q21.11 11q23-11qter 6q23.3 2q13

Genomic regions targeted by NimbleGen CGX Cytogenetic arrays:

Targeted Regions 1p36 Microdeletion 1q21.1 Microdeletion with susceptibility for thrombocytopeniaabsent radius (TAR) 1q21.1 Microdeletion with susceptibility to mental retardation, autism, or congenital anomalies 1q41-q42 Microdeletion 1q44 Microdeletion 2p15-p16.1 Microdeletion 2p21 Microdeletion, homozygous 2q32.2-q33 Microdeletion 3q29 Microdeletion 6p25.3 Microdeletion 6q24.3 Microdeletion 7q11.23 Microduplication 8p23.1 Microdeletion 9q22.32-q22.33 Microdeletion 9q34 Microdeletion 10q22.3-q23.31 Microdeletion 12q14.1-q15 Microdeletion 12q24.21-q24.23 Microduplication 14q11.2 Microdeletion 14q22-q23 Microdeletion 15q11-q13 Microduplication 15q13.3 Microdeletion 15q24.1-q24.3 Microdeletion 16p11.2 Microdeletion 16p11.2-p12.2 Microdeletion OMIM Locus 607872 Multiple 274000 Multiple Band(s) 1p36 1q21.1

Blepharophimosis, ptosis, epicanthus inversus 110100 FOXL2 (BPE) Boston-type craniosynostosis 604757 MSX2 Branchio-oto-renal (BOR)/Melnick-Fraser Buschke-Ollendorff Campomelic dysplasia (CMPD) Cat-eye 113650 EYA1 166700 LEMD3 114290 SOX9 115470 Multiple 224050 VLDLR 116860 KRIT1 603284 CCM2 603285 PDCD10 214800 CHD7 303100 CHM 119600 RUNX2 610706 FGF3 142340 CHD2, NR2F2 222400 GATA4 candidate 122470 NIPBL 158350 PTEN 304110 EFNB1 123450 Multiple 176450 MNX1 220200 ZIC1, ZIC4 188400 HIRA, TBX1 601362 Multiple 300018 NR0B1 602917 Multiple 175100 APC 145980 CASR 164280 MYCN 300581 MID2 300624 FMR1 305600 PORCN 229850 DISP1 candidate

612474 Multiple, ACP6 candidate, 1q21.1 GJA5 candidate, GJA8 candidate Multiple, DISP1 candidate 1q41 Multiple, AKT3 candidate Multiple 606407 Multiple 1q44 2p15-p16.1 2p21

119540 Multiple, SATB2 candidate 2q33.1 609425 Multiple Multiple Multiple 609757 Multiple 3q29 6p25.3 6q24.3 7q11.23

Cerebellar hypoplasia, VLDLR-related/ Hutterite dysequilibrium Cerebral cavernous malformations, type 1 (CCM1) Cerebral cavernous malformations, type 2 (CCM2) Cerebral cavernous malformations, type 3 (CCM3) CHARGE Choroideremia Cleidocranial dysplasia (CCD) Congenital deafness with inner ear agenesis, microtia, & microdontia Congenital diaphragmatic hernia (CDH) Congenital diaphragmatic hernia 2 (CDH2) Cornelia de Lange Cowden Craniofrontonasal Cri-du-Chat Currarino Dandy-Walker malformation (DWM) DiGeorge/Velocardiofacial (VCF) DiGeorge 2 Dosage-sensitive sex reversal Down syndrome critical region (DSCR) Familial adenomatous polyposis (FAP)/ Gardner/MR Familial hypocalciuric hypercalcemia 1 (HHC1) Feingold FG 5 FMR1 Microdeletion Focal dermal hypoplasia/Goltz Fryns

Multiple, GATA4 candidate 8p23.1 Multiple, TGFBR1 9q22.33 candidate 610253 Multiple, EHMT1 candidate 9q34.3 Multiple 10q22.3-q23.31

Multiple, LEMD3 candidate, 12q14.3 GRIP1 candidate Multiple 12q24.21-q24.23 Multiple, CHD8 candidate, 14q11.2 SUPT164 candidate 600037 Multiple 14q22-q23 608636 Multiple 612001 Multiple, CHRNA7 candidate Multiple 611913 Multiple Multiple 15q11-q13 15q13.3 15q24.1-q24.3 16p11.2 16p11.2-p12.2 16p13.1 16p13.3

16p13.1 Microdeletion predisposing to autism Multiple and/or mental retardation 16p13.3 Microdeletion/Severe Rubinstein-Taybi 610543 CREBBP, DNASE1 16q11.2-q12.2 Microdeletion 17q21.3 Microdeletion 22q11.2 Distal microdeletion 22q11.21 Microduplication 22q13.3 Microdeletion Xp11.22-linked mental retardation Xp11.3 Microdeletion Xp11.4-p21.2 Contiguous gene deletion Adrenal hypoplasia congenita (AHC) Alagille Albright hereditary osteodystrophylike/ Brachydactyly-MR Alpha thalassemia mental retardation (ATR-16) Androgen insensitivity Angelman Aniridia II Atrial septal defect (ASD) with atrioventricular conduction defects Bannayan-Riley-Ruvalcaba (BRRS) Bartter, antenatal 1 Bartter, antenatal 2 Bartter 3 (classic)

Multiple, SALL1 candidate, 16q11.2-q12.2 ZNF423 candidate 610443 Multiple, MAPT candidate 17q21.3 611867 Multiple 608363 Multiple, TBX1 candidate 606232 Multiple, ARSA candidate, SHANK3 candidate Multiple, HSD17B10 candidate, HUWE1 candidate 300578 Multiple, RP2 candidate, ZNF674 candidate Multiple, IL1RAPL, OTC 300200 NR0B1 118450 JAG1 600430 Multiple 141750 HBA1, HBA2 300068 AR 105830 UBE3A 106210 PAX6 108900 NKX2-5 153480 PTEN 601678 SLC12A1 241200 KCNJ1 607364 CLCNKB 22q11.2 22q11.21 22q13.3 Xp11.22 Xp11.3 Xp11.4-p21.2 Xp21.2 20p12.2 2q37.3 16p13.3 Xq12 15q11.2 11p13 5q35.2 10q23.31 15q21.1 11q24.3 1p36.13

Generalized epilepsy with febrile seizures plus 604233 SCN1A 2 (GEFS+2) Gitelman 263800 SLC12A3 Glycerol kinase deficiency (GKD) Greig cephalopolysyndactyly Hemophilia A Hemophilia B Hereditary hemorrhagic telangiectasia, type 2 Holoprosencephaly 1 Holoprosencephaly 2 Holoprosencephaly 3 Holoprosencephaly 4 Holoprosencephaly 5 Holoprosencephaly 6 Holoprosencephaly 7 Holoprosencephaly 8 Holoprosencephaly and preaxial polydactyly Holt-Oram Hypoparathyroidism, sensorineural deafness, renal disease (HDR) Hypotonia-cystinuria Infantile hyperinsulinism with enteropathy & deafness Infantile spasms, MAGI2-related Jacobsen/11q terminal deletion disorder Joubert 3 Joubert 4 300474 GK 175700 GLI3 306700 F8 306900 F9 600376 ACVRL1 236100 TRAPPC10 157170 SIX3 142945 SHH 142946 TGIF1 609637 ZIC2 605934 Multiple 610828 PTCH1 609408 Multiple 605651 FBXW11 142900 TBX5 146255 GATA3 606407 SLC3A1, PREPL 606528 USH1C, ABCC8 606382 MAGI2 147791 Multiple 608629 AHI1 609583 NPHP1

Bartter 4 (infantile with sensorineural deafness) 602522 BSND, CLCNKA & CLCNKB 1p32.3, 1p36.13 Basal cell nevus/Gorlin-Goltz Beckwith-Wiedemann, IGF2-related Beckwith-Wiedemann, KCNQ1OT1-related Benign neonatal epilepsy 109400 PTCH1 130650 IGF2 130650 KCNQ1OT1 121200 KCNQ2 9q22.32 11p15.5 11p15.5 20q13.33

Targeted Regions Joubert 5 Juvenile polyposis (JPS), BMPR1A-related Juvenile polyposis (JPS), SMAD4-related Kallmann 1 Langer-Giedion Langer mesomelic dysplasia (LMD) Leber congenital amaurosis X (LCAX) Leri-Weill dyschondrosteosis (LWD) Li-Fraumeni 1 (LFS) Lissencephaly 1 Lissencephaly with cerebellar hypoplasia Loeys-Dietz (LDS), TGFBR1-related Loeys-Dietz (LDS), TGFBR2-related Lowe Macrocephaly-autism Marfan 1 (MFS1) Marfan 2 (MFS2) McLeod Meckel 4 Menkes (MNK) Microphthalmia 3 Microphthalmia 7 with linear skin defects Miller-Dieker Mohr-Tranebjaerg Mowat-Wilson Myoclonus dystonia Nablus mask-like facial Nail-patella (NPS) Neonatal severe primary hypoparathyroidism (NSHPT) Nephronophthisis 1 Nephropathic cystinosis Neurofibromatosis 1 (NF1)/MR Neurofibromatosis 2 (NF2) Neurosensory deafness, autosomal recessive (DFNB1) NFIA haploinsufficiency Noonan 1 Noonan 4 Norrie Oculocutaneous albinism 2 (OCA2) Okihiro Opitz Ornithine transcarbamylase deficiency (OTC) Oro-facio-digital 1 (OFD1) Oto-dental Oto-facio-cervical (OFC) Pallister-Killian Parietal foramina 1 Pelizaeus-Merzbacher Peutz-Jeghers (PJS) Pitt-Hopkins Polycystic kidney disease 1 (PKD1) Potocki-Lupski/17p11.2 Microduplication Potocki-Shaffer Prader-Willi (PWS) Prader-Willi-like phenotype Proteus/Proteus-like PTEN hamartoma tumor Renal cysts and diabetes (RCAD) Retinoblastoma/MR Rieger 1 (RIEG1) Rubinstein-Taybi (RTS)

OMIM Locus 610188 CEP290 174900 BMPR1A 174900 SMAD4 308700 KAL1 150230 TRPS1, EXT1 249700 SHOX 611755 CEP290 127300 SHOX 151623 TP53 607432 PAFAH1B1 (LIS1) 257320 RELN 609192 TGFBR1 610168 TGFBR2 309000 OCRL 605309 PTEN 154700 FBN1 610380 TGFBR2 314850 XK 611134 CEP290 309400 ATP7A 206900 SOX2 309801 Multiple 247200 PAFAH1B1 (LIS1) 304700 TIMM8A 235730 ZEB2 159900 SGCE 608156 Multiple 161200 LMX1B 239200 CASR 256100 NPHP1 219800 CTNS 162200 NF1 101000 NF2 220290 GJB6 600727 NFIA 163950 PTPN11 610733 SOS1 310600 NDP 203200 OCA2 607323 SALL4 300000 MID1 311250 OTC 311200 OFD1 166750 FGF3 166780 EYA1 601803 Multiple 168500 MSX2 312080 PLP1 175200 STK11 610954 TCF4 601313 PKD1 610883 Multiple 601224 EXT2, ALX4 176270 SNRPN 176270 SIM1 176920 PTEN 158350 PTEN 137920 HNF1B 180200 RB1 180500 PITX2 180849 CREBBP

Band(s) 12q21.32 10q23.2 18q21.2 Xp22.31 8q23.3, 8q24.11 Xpter-Xp22.3 & Ypter-Yp11.32 12q21.32 Xpter-Xp22.3 & Ypter-Yp11.32 17p13.1 17p13.3 7q22.1 9q22.33 3p24.1 Xq25 10q23.31 15q21.1 3p24.1 Xp21.1 12q21.32 Xq21.1 3q26.33 Xp22.2 17p13.3 Xq22.1 2q22.3 7q21.3 8q21.3-q22.1 9q33.3 3q21.1 2q13 17p13.3 17q11.2 22q12.2 13q12.11 1p31.3 12q24.13 2p22.1 Xp11.3 15q13.1 20q13.2 Xp22.2 Xp11.4 Xp22.2 11q13.3 8q13.3 12p 5q35.2 Xq22.2 19p13.3 18q21.1 16p13.3 17p11.2 11p11.2 15q11.2 6q16.3 10q23.31 10q23.31 17q12 13q14.2 4q25 16p13.3

Targeted Regions Saethre-Chotzen Schizencephaly Senior-Loken 6 Severe myoclonic epilepsy of infancy (SMEI) Sex reversal, autosomal dominant 2 (SRA2)

OMIM Locus 101400 TWIST1 269160 EMX2 610189 CEP290 607208 SCN1A

Band(s) 7p21.1 10q26.11 12q21.32 2q24.3

154230 Multiple, DMRT1 candidate 9p24.3 1q25.2 Xq26.2 11q13.4 17p11.2 5q35.3 7q31.1 7q21.3 10q24.32 3q28 2q31.1 Yp11.31 Xp22.31 12q13.11 2q31.1 16q12.1 8q23.3 9q34.13 16p13.3 12q24.21 1q32.2 6p21.1 3p25.3 2q36.1 3p14.1 11p13 22q12.3 7q11.23 11p13 4p16.3 Xq22.1 Xq22.3 Xq22.3 Xp11.4 Xq26.3 Xq28 Xpter-Xp22.3, Ypter-Yp11.32 Xp21.3 Xp22.13 Xp22.13 Xq22.3 Xp21.3 Xq25 Xp21.3 Xq22.3 Xp21.3 Xq27.1 Xp11.4 Yp11.31 Yp11.31 9q33.3 41 sites 43 sites 24 chromosomes

Short stature, pituitary and cerebellar defects, 262700 LHX4 small sella turcica Simpson-Golabi-Behmel (SGBS) 312870 GPC3 Smith-Lemli-Opitz (SLOS) Smith-Magenis (SMS) Sotos Speech & language disorder 1 Split-hand/foot malformation 1 (SHFM1) Split-hand/foot malformation 3 (SHFM3) Split-hand/foot malformation 4 (SHFM4) Split-hand/foot malformation 5 (SHFM5) SRY dosage abnormalities Steroid sulfatase deficiency Stickler I Synpolydactyly/Syndactyly II Townes-Brocks 1 Trichorhinophalangeal 1 Tuberous sclerosis 1 (TSC1) Tuberous sclerosis 2 (TSC2) Ulnar-mammary Van der Woude Vascular endothelial growth factor (VEGFA)related disorders von Hippel-Lindau Waardenburg I Waardenburg IIA WAGR Walker-Warburg, LARGE-related Williams-Beuren Wilms Tumor 1 Wolf-Hirschhorn X-linked agammaglobulinemia X-linked Alport (ATS) X-linked Alport plus diffuse leiomyomatosis (ATS-DL) X-linked chronic granulomatous disease X-linked heterotaxy X-linked hydrocephalus and nephrogenic diabetes insipidus X-linked idiopathic short stature (ISSX) X-linked infantile spasms, ARX-related X-linked infantile spasms, CDKL5-related X-linked juvenile retinoschisis X-linked lissencephaly X-linked lissencephaly with ambiguous genitalia X-linked lymphoproliferative (XLP) X-linked mental retardation 21 X-linked mental retardation 30 X-linked mental retardation 54 270400 DHCR7 182290 RAI1 117550 NSD1 602081 FOXP2 183600 SHFM1 600095 FBXW4 605289 TP63 606708 DLX1, DLX2 278850, SRY 306100 308100 STS 108300 COL2A1 186000 HOXD, gene cluster 107480 SALL1 190350 TRPS1 191100 TSC1 191100 TSC2 181450 TBX3 119300 IRF6 192240 VEGFA 193300 VHL 193500 PAX3 193510 MITF 194072 PAX6, WT1 236670 LARGE 194050 ELN 194070 WT1 194190 Multiple 300755 BTK 301050 COL4A5 301050 COL4A5, COL4A6 306400 CYBB 306955 ZIC3 L1CAM, AVPR2 300582 SHOX 308350 ARX 300672 CDKL5 312700 RS1 300067 DCX 300215 ARX 308240 SH2D1A 300143 IL1RAPL1 300558 PAK3 300419 ARX

X-linked mental retardation with isolated 300123 SOX3 growth hormone deficiency X-linked mental retardation with microcephaly & 300749 CASK disproportionate pontine and cerebellar hypoplasia XX male 278850 SRY XY gonadal dysgenesis XY sex-reversal, +/- adrenal failure All 41 unique subtelomeric regions All 43 unique pericentromeric regions/marker chromosomes Aneuploidy for 24 chromosomes 400044 SRY 184757 NR5A1 Multiple Multiple Multiple

For life science research only. Not for use in diagnostic procedures.
NIMBLEGEN is a trademark of Roche. GENOGLYPHIX and SIGNATURE GENOMICS are trademarks of Signature Genomic Laboratories, LLC. Other brands or product names are trademarks of their respective holders.

05895529001 u 04/10

Published by: Roche Diagnostics GmbH Roche Applied Science Werk Penzberg 82372 Penzberg Germany

www.roche-applied-science.com 2010 Roche Diagnostics GmbH All rights reserved.