Cardiovascular Genetics: Focus on Genetics of Coronary Artery Disease
The human genome is comprised of 3.2 billion nucleotide (base) pairs of which ~30 million base pairs or 1 % code for proteins.
Each genome contains approximately 4 million sequence variants (DSVs) of which 3.5 million involve a single nucleotide and are referred to as single nucleotide variants (SNVs) or polymorphisms (SNPs)
Single gene disorders are causes by SNVs that exert very large effects on the phenotype. Therefore, the phenotype exhibit clear patterns of inheritance, such as a dominant or a recessive pattern
Polygenic disorders are caused by the cumulative effects of a very large number of DSVs each exerting a modest effect on the phenotype.
The clinical phenotype, even in single gene disorders, is a complex phenotype caused by the contributions of not only the causal variant but also the effects of a large number of the modifier variants, epigenetic factors, non-coding RNAs and the environmental factors.
CAD is a quintessential complex phenotype caused by the complex, stochastic and often non-linear interactions between genetic, genomic, proteomics and the environmental factors, among the others
Genome-wide association studies have led to identification of over 100 SNVs associated with CAD
The newly identified susceptibility loci offer new mechanisms for the pathogenesis of CAD and therefore, potentially new therapeutic targets
KeywordsGenetics Coronary artery disease Atherosclerosis Complex trait DNA sequencing
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