WES

1. Clinical indications

Family with a history genetic disease
Patients with atypical disease characteristics without diagnosis
Patients with physical and mental disabilities
Couples who want to check the reason of recurrent miscarriage or stillbirth
Patients who have failed to find a genetic cause by clinical exome sequencing

2. Technology

Wet lab(Genomic DNA)

Illumina NovaSeq 6000; Capture based tech (nano WES / IDT / Agilent probe)
Average 100X sequencing coverage, Q30 > 90%, 20X coverage rate > 95%

Dry lab (Bioinformatics)

VeritaTrekker Variants Detection System (SNVs, CNVs, InDels)
Enliven Data Annotation and Interpretation System
Cruxome Interface

* For the specific clinical exome sequencing (CES), gene panel covers 5,462 genes associated with known autosomal recessive, autosomal dominant and X-linked diseases listed in the Online Mendelian Inheritance in Men (OMIM) catalogue.

3. Case sharing

Two female siblings originally diagnosed with “cerebral palsy” had received long-term treatment with no significant improvement in perennial paralysis and language skills. Family WES tests found that both girls inherited pathogenic mutations in the GCH1 gene associated with the metabolic disease Dopa-responsive dystonia (DRD). Both girls have now been successfully effectively treated by oral Medopa (Benserazide-Levodopa), reducing the severity of symptoms and improving their quality of life. This case fully demonstrates the important role of WES in the precise diagnosis and treatment of genetic diseases.

4. Why choose Berry Genomics for WES

Integrated professional teams for sequencing, data analysis and reporting
Fast turnaround time
Comprehensive disease report for clinical geneticist, including supplementary file listing all potentially pathogenic mutations
Option of uploading raw data by Cloud to local hospitals for secure storage and reanalysis options
Competitive pricing

5. The clinical significance of WES/CES

Can provide a precise diagnosis for children with unexplained phenotypes where previous testing has failed to give the answer
Can help explain the genetic basis of fetal structural abnormalities detected by ultrasound during pregnancy
Can point the way to potential treatment options for children to improve their health and quality of life
Can guide the development of prenatal and preimplantation genetic tests so couples
can confidently proceed to have a second child free of the familial disease condition

CNV-Seq

1. Clinical indications

Postnatal

Children or adults with unexplained disease symptoms (Peripheral blood DNA)

Prenatal

Miscarriage products of conceptions (chorionic villus DNA)
Fetal ultrasound structural abnormalities (amniocyte DNA)
High risk pregnancies (advanced maternal age, soft ultrasound marker)

2. Technology

Wet lab

Patent PCR-free library construction technology
Low input: 10-50ng DNA
Detection of aneuploidy, large fragment deletion/duplication, whole genome CNVs (>100kb), chromosome mosaicism (>10%)

Dry lab (Bioinformatics)

CNV analysis system

3. Case sharing – apoblema testing

Clinical information:

31 yrs, induced labor one time, a biochemical pregnancy, six times of embryo arrest. She did such test at 7+3 weeks, no fetal buds or fetal heart.

Test results:

seq [hg19] dup(2)(q36.1q37.3)
chr2:g. 224740001_243020000dup
seq [hg19] del(8)(q24.23q24.3)
chr8:g. 138800001_146300000del

CNV-seq identified terminal deletion/duplication events at the end of chromosomes 2 and 8, indicating an balanced translocation.

Follow up FISH verified that the husband had t(2;8)(q36.1;q24.23) balanced translocation. The couple choose PGT and they successfully achieved a healthy baby.

4. Why choose Berry Genomics for CNV-Seq

Low cost
Integrated professional teams for sequencing, data analysis and reporting
Fast turnaround time
Reliable and accurate results equivalent to current array CGH and SNP arrays

5. The clinical significance of CNV-Seq

Can detect aneuploidy, CNVs (resolution 0.1Mb) and mosaicism (resolution) that are associated with known chromosome disease syndromes
Applicable to genetic diagnosis of preconception, prenatal and postnatal samples
Can identify a genetic cause of miscarriage samples
Reliable results can be obtained from rare samples or samples with low amounts of DNA

RNA-seq

1. Introduction

Comprehensive and rapid transcriptome sequencing for human, animals and plants samples under a certain tissue or cell states. FOR RESEARCH ONLY.
Sample type: dsDNA generated from polyA+ mRNA

2. Technology

Illumina NovaSeq 6000
Validated sequencing pipeline
More accurate detection of gene expression changes
No need to design new probes for known sequences, saving time and cost

3. Case sharing – Arabidopsis blue light receptor protein

RNA-Seq helps demonstrate the photo-induced protein dimerization of plant cryptochromes is a key step in their primary photoreaction.

^Qin Wang, Zecheng Zuo, Chentao Lin, et al., Photoactivation and inactivation of Arabidopsis cryptochrome 2. PLANT PHOTOBIOLOGY.(2016),VOL 354 ISSUE 6310.

WGS (Human)

1. Introduction

Offers genome wide detection of DNA variants including SNP, CNV, Indel and SV
Ability to detect rare and novel (de novo) genetic variants
Applicable to patients whose WES has failed to detect pathogenic variants
Sample type: Genomic DNA

2. Technology

Wet lab

NovaSeq 6000
Average sequencing depth ≥30X

Dry lab (Bioinformatics)

Berry own database (0ver 400,000 cases)

3. Case sharing – gastric cancer-related genetic variation information

Gastric cancer is a heterogeneous disease with different molecular etiologies. We performed WGS of 100 pairs of tumor-normal samples at an average effective sequencing depth of 84X. Bioinformatics analysis identified tumour-specific somatic mutations in known genes such as TP53, ARID1A, CDH1 and in a newly discovered gene MUC6. Mutations in driver genes were also found including CTNNA2, GLI3, and RNF43. The study also revealed that that 4.3% of RHOA mutations in diffuse tumors were closely related to the most common interference pathways (adhesion links and focal adhesions) in gastric cancer.

4. Why choose Berry Genomics for WGS

Output as high as 200,000 Gb raw data per week
Integrated professional teams for sequencing, data analysis and reporting
Fast TAT to report of 25 days
Comprehensive disease report for clinical geneticist, including supplementary file listing all potentially pathogenic mutations
Option of uploading raw data by Cloud to local hospitals for storage and reanalysis

Kai Wang, Siu Tsan Yuen, et al., Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nature Genetics. (2014),doi:10.1038/ng.2983.

WGS (Animal or Plant)

1. Introduction

The genome-wide sequencing of animals and plants genomes is important to understand differences in species and varieties. The information can be used for population genetic polymorphism analysis, evolutionary analysis, identification of new functional genes, breeding guidance and genetic modifications.

2. Technology

NovaSeq 6000
Obtain information on CDS, Introns, intergenic regions
SNP, CNV, InDel, SV and other variation information
Structural variations and genomic CNVs in large fragments

3. Case sharing – Genome-wide resequencing for Soybean

Identification of domesticated and improved genes in the soybean genome is important for guiding soybean breeding. Three types of germplasm lines were selected in this study. A total of 302 representative soybean germplasm resources were sequenced at a depth was greater than 11X. The results showed that the genetic polymorphism of soybean was significantly reduced during acclimation and improvement. Genome-wide association analysis on seed size, seed coat color, growth habit, oil content and other traits identified a series of significant associated genetic sites.

The decline of linkage imbalance (LD) in GWAS analysis of soybean genomic population

Zhou Z, Jiang Y, et al., Resequencing 302 wild and cultivated accessions genes related to domestication and improvement in soybean. Nat Biotechnol.(2015),doi:10.1038/nbt.3096.

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