Services

Analysis of over 450 disease-causing genes that affect the optic nerve and the anterior and posterior segment of the eye.

16 specific gene panels associated with more than 50 ocular disorders.

Panels specifically designed to perform NGS analysis of all the coding, flanking exonic-intronic regions (NCSS Non Canonical Splice Sites) regions and the mutations located in internal regions of the introns (deep-intronic) of the genes specified in each panel.

Whole Exome Sequencing (WES) (>90x; Sequencing Gb read length 2×100, NovaSeq 6000) of all coding regions of the genome for the identification of mutations in genes not included in the panels.

Whole Genome Sequencing (WGS) (>30X; Sequencing Gb read length 2×100, NovaSeq6000) of all coding and non-coding regions of the genome to identify large genomic rearrangements, copy number variants (CNVs) of specific sequences, and pathogenic variants located in deep-intronic regions.

Sanger sequencing for the validation of putative pathogenic variants and, in specific cases, to identify and locate low-covered regions of candidate genes.

Bioinformatic analysis for the identification and annotation of the variants according to the CNAG-CRG pipeline (National Center for Genomic Analysis-Center for Genomic Regulation, Barcelona) and subsequent filtering for the prioritization of the genetic variants selected using in house scripts based on the expertise and deep experience of the DBGen team.

Availability of functional studies on demand to demonstrate the pathogenicity of novel variants.

On demand reanalysis service to identify new genetic variants with clinical relevance to complement a previous diagnosis.

Personalized genetic counseling to the proband and relatives. More info.

Updated information on gene therapies in advanced clinical phases and those already available.

fast and reliable results
excellent diagnostic performance in difficult cases
ease of communication with patients, specialists and companies

Results

A detailed genetic report will be provided that will include the identified genetic variants and genetic counseling. This information is based on exhaustive bibliographic studies, database analysis and, especially, the expertise of the DBGen team  supported by more than 25 years of research in the genetics of hereditary eye disorders. Thishigh degree of specialization guarantees a high diagnostic efficiency (>80%) providing relevant data for clinical differential diagnosis.
The report turnaround time is between 12 and 14 weeks upon receipt of the sample.

Methodologies we use

DBGen uses three strategies for genetic diagnosis based on automated DNA sequencing on NovaSeq 6000 Sequencing System (Illumina) platforms, specially designed for this type of high-throughput analysis. The final objective is to offer an accurate and reliable genetic diagnosis, identifying the gene(s) responsible for the patient’s pathology.

Gene panels
Used to focus the diagnosis toward genomic fragments in coding regions (exons) for genes that cause eye diseases. Our panels have been carefully designed to identify: the coding regions of the genes specified in each panel, the exon-intron boundaries (± 25 nucleotides) and the deep-intronic regions, in which mutations have been reported. Besides, low-covered regions have been reinforced to ensure diagnostic success.
Single-nucleotide variants (SNVs) are validated by Sanger sequencing. Concerning novel genetic variants, we verify that their frequency in the control population is less than 1% and that they comply with the pathogenicity predictions following the established bioinformatic algorithms (SIFT, LRT, MutationTaster, PolyPhen2, CADD and NetGene2).The classification of the new variants is carried out according to the American College of Medical Genetics and Genomics criteria (Richards et al. Gene / Med. 2015; 17: 405-24) and recommendations of the European Society of Human Genetics (Matthijs et al. Eur J Hum Genet. 2016; 24,2-5)

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Exome (WES)
Used to simultaneously sequence all of the coding regions (exons) of the patient’s genome (some 20,000 genes) on NovaSeq6000 platforms (Illumina) and, based on the sequence analysis, the genetic variants responsible for inherited eye diseases are prioritized. Bioinformatics prioritization is based on genetic and population criteria by comparison with databases of control populations. If the clinical diagnosis is not clearly defined, the study of the exome is the most effective methodological strategy for genetic diagnosis, since it allows a simultaneous analysis of all the coding regions of the genome and to identify new causative genes. However, genomic rearrangements of large DNA fragments, or genetic variants in non-coding regions (introns and regulatory sequences) will remain undetected.
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Genome (WGS) 

All the coding (exons) and noncoding regions (introns and regulatory sequences) of the patient’s genome are sequenced simultaneously. It is the strategy of choice for the identification of large genomic rearrangements, copy number variations (CNVs) and deep-intronic mutations.

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State-of-the-art methodologies

Based on its extensive research experience, DBGen can also perform additional tests to identify large genomic rearrangements, and functional tests of potentially pathogenic genetic variants. These studies will be carried out on demand, as will be regarded as research work.