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Cytoonearray-Clinical Diagnostic Tool

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Targeted chromosomal microarray for detecting abnormalities related to micro-deletions and micro-duplications Detects chromosomal abnormalities and familial diseases of fetuses and infants. High-density probe deployment, detecting chromosomal micro-deletions and micro-duplications. In addition to detecting aneuploidy diseases (such as Down's syndrome), CytoOneArray can simultane- ously detect 372 genetic abnormalities (331 diseases and 41 sub-telomeric regions). Emphasis on detecting developmental delays (DD) and intellectual disabilities (ID). Excludes common CNVs in non-specific areas. From analyzing data to the report output, CytoOneArray is easy to operate with our software! [ Array Spec. ] 2 0 Database UCSC hg19 -2 Probe length 57-63 mer only reports disease-related CNVs Disease regions 331 Subtelomeres 41 Disease region 10 - 30 Kb probe resolution 2 0 Total probes 33,255 -2 、 Sample type blood amniotic fluid DNA、tissue Other CMAs report benign CNVs, which may affect clinical interpretation. Missing pathogenic regions may also lead to medical disputes. Application Postnatal Testing • Identifies chromosomal abnormalities from blood DNA • Provides relevant phenotype information • Similar to performing 372 FISH experiments simultaneously Prenatal Testing • Identifies chromosomal abnormalities from amniotic fluid cell DNA • Provides relevant genotype information • Offers a much higher diagnostic yield Process Requisition form & Sample Array Report Informed consent Collection Analysis Explains test results 1 Comparisons with Other Methods FISH Chromosomal Method Karyotyping (Fluorescence in situ microarray Hybridization) Target ChromosomeChromosome fragment Chromosome fragment Resolution 5 - 10 Mb 10 Kb - 100 Kb 10 - 50 Kb To detect specified To detect micro- To detect chromosome Major micro-duplications, duplications and number and large micro-deletions and micro-deletions application physical abnormality structural changes across whole genome Unable to detect Need to know Unable to discriminate Limitation micro-duplications abnormal chromosome balanced chromosome and micro-deletions position prior to test structural changes David Miller et al. The American Journal of Human Genetics 86, 749–764 (2010) Chromosomal microarray analysis should be the first-line genetic test in pregnancies where ultrasound screens uncover signs of fetal abnormalities, according to the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine. ACOG committee opinion, Number 581 (2013) 2 Perfect Support CytoOneArray provides an integrated service system, which starts from array design, to process control of detection, to report generation (Figure A). Figure B depicts an online disease database available to physicians after report generation. This chain of services was designed to assist the diagnosis. A. Software From analyzing data to generating a report, everything is simple and secure! [鍵入文字] 華聯染色體晶片檢測報告 報報告告編編號號 CY2013-00-000-v1 採採樣樣日日期期 2014-6-6 收收檢檢日日期期 2014-6-8 檢檢體體編編號號 CY2013-00-000 檢檢體體類類別別 羊水 送送檢檢原原因因 高齡產婦; 有家族遺傳病史 送送檢檢醫醫師師 ○○○醫師 報報告告日日期期 2014-06-20 諮諮詢詢專專線線 (03)578-1168 分機 506 [email protected] 華聯生技股份有份公司 www.OneArray.com 0800-777-988 - 0 - [email protected] CytoOA-tw-postnatal V1.0 B. Online disease database References for diagnosis Multiple search tools • by Key word • by Cytoband • by Disease name Link to OMIM database 300068 ANDROGEN INSENSITIVITY SYNDROME; AIS Alternative titles; symbols TESTICULAR FEMINIZATION SYNDROME; TFM ANDROGEN RECEPTOR DEFICIENCY Cytogenetic location: Xp12 Gene Phenotype Relationships Disease info & reference Chromosome 1p36 deletion syndrome 1p36 607872 Deletion of 1p36.13 to 1p36.33, major in 1p36.2 Growth retardation, pre- and postnatal, Eyes/Ears deafness, and abnormal in appearance. (Detail) GeneReviews: 1p36 deletion syndrome 3 Demo Report Abnormality result is reported: Chromosomal Microarray Result ISCN nomenclature arr 7q11.23 (72,726,605-74,096,842)x1 Dosage Variation 1.370 Mb-microdeletion at chromosome 7q11.23 was detected. No . 7 chr. Abnormal chromosome Analysis Result Interpretation： 1.370 Mb-microdeletion at chromosome 7q11.23 was detected. According to the clinical literature, Williams- Beuren syndrome (WBS) is a contiguous gene deletion syndrome resulting from the deletion on chromosome 7q11.23. Chromosome Ideogram: Copy-number variations (CNVs) are displayed on the corre- sponding locations in the genome. Red regions indicate copy-number losses, and blue regions indicate copy-number gains. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X Y 4 Disease Name Cytoband OMIM Disease Name A ACMG Autism possible region 2q37.1 – Chromosome 2q24.3 deletion ACMG Autism possible region 13q14.2 – Chromosome 3pter-p25 deletion syndrome ACMG Autism possible region 18q21.1 – Chromosome 3q29 microdeletion syndrome Adrenal hypoplasia, congenital (AHC) Xp21.2 300200 Chromosome 4p16.1 duplication Adrenoleukodystrophy (ALD) Xq28 300100 Chromosome 4q21 deletion syndrome Agammaglobulinemia, X-linked 1 (XLA) Xq22.1 300755 Chromosome 6p22 deletion Alagille syndrome 1 (ALGS1 ) 20p12.2 118450 Chromosome 6pter-p24 deletion syndrome Albinism, oculocutaneous, type II (OCA2) 15q12-q13.1 203200 Chromosome 7q31.2 microdeletion/microduplication Alpha thalassemia/mental retardation syndrome 16p13.3 141750 Chromosome 8p22-p23.1 duplication Alport syndrome, X-linked (ATS) Xq22.3 301050 Chromosome 8q11 duplication Alzheimer disease 1, familial (AD1) 21q21.3 104300 Chromosome 8q21 microdeletion ~ A Androgen insensitivity syndrome (AIS) Xq12 300068 Chromosome 9p deletion syndrome Angelman syndrome (AS ) 15q11.2-q13.1 105830 Chromosome Xp11.3 deletion syndrome Aniridia (AN) 11p13 106210 Chromosome Xp22 deletion syndrome K Asperger syndrome,X-linked, susceptibility to, 1 (ASPGX1) Xq13.1 300494 Chronic granulomatous disease, X-linked (CGD) Autism (contain A2BP1 gene) 16p13.3 – Cleft palate, isolated (CPI) Autism (contain ANKRD11 gene) 16q24.3 – Cleidocranial dysplasia (CCD) Autism (contain CDH8 gene) 16q21 – Coffin-Lowry syndrome (CLS) Autism (contain CNTNAP1 gene) 17q21.2-q21.31 – Cornelia de Lange syndrome 1 (CDLS1) Autism (contain DLGAP2 gene) 8p23.3 – Cornelia de Lange syndrome 2 (CDLS2) Autism (contain DPP10 gene) 2q14.1 – Cortical dysplasia-focal epilepsy syndrome Autism (contain DPP6 gene) 7q36.2 – Cowden syndrome 1 (CWS1) Autism (contain NLGN1 gene) 3q26.31 – Craniofacial dysostosis with short stature Autism (contain PCDH9 gene) 13q21.32 – Craniofrontonasal syndrome (CFNS) Autism susceptibility 15 (AUTS15) 7q35-q36.1 612100 Craniosynostosis, type 2 (CRS2) Autism susceptibility 16 (AUTS16) 3q24 613410 Cri-du-Chat syndrome Autism susceptibility 17 (AUTS17) 11q13.3-q13.4 613436 Currarino syndrome Autism susceptibility 6 (AUTS6) 17q11.2 609378 Cystinosis, Nephropathic (CTNS) Autism susceptibility, X-linked 2 (AUTSX2) Xp22.32-p22.31 300495 D Dandy-Walker syndrome (DWS) Autism, susceptibility to, X-linked 3 (AUTSX3) Xq28 300496 Danon disease Axenfeld-Rieger syndrome, type 1 (RIEG1) 4q25 180500 Deafness, autosomal dominant 10 (DFNA10) Axenfeld-Rieger syndrome, type 3 (RIEG3) 6p25.3 602482 Diaphragmatic hernia 2 (DIH2) B Bannayan-Riley-Ruvalcaba syndrome (BRRS) 10q23.2-q23.31 153480 Diaphragmatic hernia 3 (DIH3) Bartter syndrome, antenatal, type 2 11q24.3 241200 Diaphragmatic hernia, congenital Basal cell nevus syndrome (BCNS) 9q22.32 109400 DiGeorge syndrome (DGS) Beckwith-Wiedemann syndrome (BWS) 11p15.5-p15.4 130650 DiGeorge syndrome/velocardiofacial syndrome complex-2 Blepharophimosis, ptosis, and epicanthus inversus (BPES) 3q22.3-q23 110100 DiGeorge syndrome/velocardiofacial syndrome complex-2 Borjeson-Forssman-Lehmann syndrome (BFLS) Xq26.2 301900 Dihydropyrimidine dehydrogenase deficiency Brachydactyly, type C (BDC) 20q11.22 113100 Down syndrome Brachydacytly-mental retardation syndrome (BDMR) 2q37.3 600430 Duane-radial ray syndrome (DRRS) Branchiootorenal syndrome 1 (BOR1) 8q13.2-q13.3 113650 Dyggve-Melchior-Clausen disease (DMC) Buschke-Ollendorff syndrome (BOS) 12q14.2-q14.3 166700 E Epilepsy, childhood absence, susceptibility to, 5 (ECA5) C Campomelic dysplasia (CMPD) 17q24.3 114290 Epilepsy, X-linked, with variable learning disabilities and Cardiomyopathy, dilated, 1J (CMD1J) 6q23.2 605362 behavior disorders Cat eye syndrome (CES) 22q11.1-q11.21 115470 Epileptic encephalopathy, early infantile, 1 (EIEE1) Cerebral creatine deficiency syndrome 1(CCDS1) Xq28 300352 Epileptic encephalopathy, early infantile, 1 (EIEE1) Charcot-Marie-Tooth disease type 1A (CMT1A ) 17p12 118220 Epileptic encephalopathy, early infantile, 3 (EIEE3) CHARGE syndrome 8q12.1-q12.2 214800 Epileptic encephalopathy, early infantile, 4 (EIEE4) Chondrodysplasia punctata 1, X-linked recessive (CDPX1) Xp22.33 302950 Epileptic encephalopathy, early infantile, 6 (EIEE6) Chondrodysplasia, Grebe type 20q11.22 200700 Epileptic encephalopathy, early infantile, 8 (EIEE8) Choroideremia (CHM) Xq21.2 303100 Epileptic encephalopathy, early infantile, 9 (EIEE9) Chromosome 10q23 deletion syndrome 10q23.1-q23.31 612242 F Fabry disease Chromosome 10q26 deletion syndrome 10q26.3 609625 Familial adenomatous polyposis 1 (FAP1) Chromosome 12p13 microdeletion 12p13.31 – Feingold syndrome 1 (FGLDS1) Chromosome 12q24.21-q24.23 microduplication 12q24.21-q24.23 – Focal dermal hypoplasia (FDH) Chromosome 13q12 microduplication 13q12.11 – Forebrain defects Chromosome 13q33q34 microdeletion 13q33.3-q34 – Fragile X mental retardation syndrome Chromosome 14q11-q22 deletion syndrome 14q11.2 613457 G Glycerol kinase deficiency
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  • Whole Exome Sequencing Gene Package Intellectual Disability, Version 9.1, 31-1-2020

    Whole Exome Sequencing Gene Package Intellectual Disability, Version 9.1, 31-1-2020

    Whole Exome Sequencing Gene package Intellectual disability, version 9.1, 31-1-2020 Technical information DNA was enriched using Agilent SureSelect DNA + SureSelect OneSeq 300kb CNV Backbone + Human All Exon V7 capture and paired-end sequenced on the Illumina platform (outsourced). The aim is to obtain 10 Giga base pairs per exome with a mapped fraction of 0.99. The average coverage of the exome is ~50x. Duplicate and non-unique reads are excluded. Data are demultiplexed with bcl2fastq Conversion Software from Illumina. Reads are mapped to the genome using the BWA-MEM algorithm (reference: http://bio-bwa.sourceforge.net/). Variant detection is performed by the Genome Analysis Toolkit HaplotypeCaller (reference: http://www.broadinstitute.org/gatk/). The detected variants are filtered and annotated with Cartagenia software and classified with Alamut Visual. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes). HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x A2ML1 {Otitis media, susceptibility to}, 166760 610627 66 100 100 96 AARS1 Charcot-Marie-Tooth disease, axonal, type 2N, 613287 601065 63 100 97 90 Epileptic encephalopathy, early infantile, 29, 616339 AASS Hyperlysinemia,