Targeted sequencing of genes associated with inherited diseases
The xGen Inherited Diseases Panel enables deeper sequencing of genomic regions containing genes and SNPs associated with inherited diseases. The gene list is based on the HGMD® (Human Gene Mutation Database) repository of known inherited disease-causing mutations.
Whole exome sequencing has traditionally been the standard method for detecting a wide variety of inherited diseases. However, focused sequencing of specific genomic regions of interest provides deeper coverage for easier, more efficient, and more accurate detection of disease-causing mutations. The xGen Inherited Diseases Panel targets all disease-causing mutations as defined by the HGMD database, combining the ease of whole exome sequencing with the low per sample cost of targeted panels.
The xGen Inherited Diseases Panel consists of 116,355 xGen Lockdown Probes, spanning 11.1 Mb of the human genome, designed for targeted enrichment of genes and SNPs associated with the inherited diseases listed. xGen Lockdown Probes are individually synthesized and quality controlled 120mer oligonucleotides bearing a 5′ biotin modification and manufactured using proprietary Ultramer® synthesis technology.
Autism spectrum disorders
Congenital disorders of glycosylation
Congenital nyasthenic syndromes
Epilepsy and seizure disorders
Glycogen storage disorders
Hereditary cancer syndrome
Hereditary periodic fever syndromes
Inflammatory bowel disease
Lysosomal storage disorders
Maturity onset diabetes of the young
Multiple epiphyseal dysplasia
Noonan syndrome and related disorders
Peroxisome biogenesis disorders, Zellweger syndrome spectrum
Short stature panel
X-linked intellectual disability
The data presented in Figures 1–3 demonstrate the excellent performance of the xGen Inherited Diseases Panel. Data are normalized to 25M reads. The average sample insert size was 344 bases with a standard deviation of 35 bases. The range of on-target reads was 14.3–14.9M with 4.6–5% duplicate reads.
Figure 1. Highly uniform coverage from xGen Inherited Diseases Panel. Uniformity of coverage of the target regions is represented here as proportion of targets with >0.2 x mean coverage (blue), >0.5 x mean coverage (green) and >1.0 x mean coverage (grey). The data demonstrate that with a mean coverage depth of 100X, 99% of the targets captured using the xGen Inherited Diseases Panel will have >20X depth of coverage. Error bars indicate standard deviation from the mean.
Figure 2. Complete coverage of targeted regions using xGen Inherited Diseases Panel. Uniformity of coverage for 2 replicate captures using the xGen Inherited Diseases Panel were compared. The 2 experiments showed practically identical coverage, with both achieving 98.7% of all targets covered at ≥30X using 25M reads on the Illumina MiSeq® Sequencing System (300-base paired-end reads).
Figure 3. High reproducibility obtained using xGen Inherited Diseases Panel. A comparison of target-by-target coverage between 2 sample replicates captured using the xGen Inherited Diseases Panel shows excellent reproducibility, with an R2 value of 0.9622, demonstrating the consistent, high performance of the panel.