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NGS Sequencing for Management of Cardiovascular Disorders
Current PCR-based strategies are inadequate for genomic investigations involving
many candidate genes. NGS has overcome such limitations so that comprehensive
testing is now feasible for clinically complex cases. WGS is currently used only for
highly selected, clinically complex cases but with rapidly dropping test costs and
increasing accuracy, it will eventually replace most, if not all, currently offered
genetic tests (Teekakirikul et al. 2013 ). A NGS procedure associated with DNA
sequence capture has been reported that can sequence 202 cardiomyopathy-related
genes simultaneously (D’Argenio et al. 2014 ). The authors developed a complemen-
tary data analysis pipeline to select and prioritize genetic variants. The overall pro-
cedure can screen a large number of target genes simultaneously, thereby potentially
revealing new disease-causing and modifi er genes. By using this procedure, hyper-
trophic cardiomyopathy patients can be analyzed in a shorter time and at a lower
cost than with current procedures. The specifi city of the NGS-based procedure is at
least as good as other techniques routinely used for mutation searching, and the
sensitivity is much better. It will facilitate personalized approach to treatment.
SNP Genotyping in Cardiovascular Disorders
Illumina has developed a custom SNP biochip for the study of vascular diseases
through a collaboration with the Institute of Translational Medicine and
Therapeutics (ITMAT) at the University of Pennsylvania, the Broad Institute at
MIT, and the National Heart, Lung, and Blood Institute (NHLBI)’s Candidate-gene
Association Resource (CARe) Consortium. The IBC chip, named for ITMAT,
Broad, and CARe, has been used to analyze SNPs in genes that have been selected
for cardiovascular- related phenotypes. Illumina iSelect Custom Genotyping
BeadChip can be used to study the genetic diversity of pathways for >2,000 genes
that are linked to vascular conditions including hypertension, myocardial infarc-
tion, heart failure, stroke, insulin resistance, metabolic disorders, dyslipidemia, and
infl ammation. The iSelect BeadChip enables scientists to train their research on
specifi c SNPs related to pathways or disease. The microarray will enable research-
ers to quickly genotype thousands of patients across thousands of genes to identify
genetic risk factors underlying vascular diseases and other complex genetic traits.
Typing of specifi c SNPs in the genome of an individual helps in diagnosing or
detecting susceptibility to cardiovascular disease. Common SNPs at 18 loci are
reproducibly associated with concentrations of LDL cholesterol, HDL cholesterol,
and/or triglycerides. Six of these loci are new, and of these two are associated with
LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2
and PBX4), one with HDL cholesterol (1q42 in GALNT2) and fi ve with triglycer-
ides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13
near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated
SNP is also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels
in human liver, and a proxy for this SNP has been shown to affect risk for coronary
14 Personalized Management of Cardiovascular Disorders