Copy Number Variation in the Human Genome and Its Implications for Cardiovascular Disease

Abstract

U nlocking the information contained within the human genome will likely advance our understanding of cardiovascular (CV) health and disease by leading to discovery of new molecules, pathways, and networks. A central strategy in genetic studies of CV disease has been to correlate human genomic DNA variation with clinical phenotypes, such as myocardial infarction, heart failure, stroke, and their risk factors, with a range of experimental designs and analytical procedures. The ability to detect genomic differences between individuals is the foundation of this research. Human genomic variation exists in many forms, each of which has unique qualitative and quantitative features. Each form of human genomic variation is composed of many individual variants that occur across the genome. The population frequency of individual variants can range from rare to common. The effect of a specific genomic variant can range from beneficial to neutral to deleterious. To rapidly translate genomic knowledge into diagnosis and treatment of CV disease, it is logical to search for common genomic variants that have a non-neutral impact. In the recent past, one form of genomic variation, the single-nucleotide variant, has dominated the experimental landscape: It is the currency of present genetic CV disease studies. However, recent developments indicate that the focus on single-nucleotide polymorphisms (SNPs) alone will not capture the full range of meaningful human genomic variation, such as a newly characterized and annotated form called copy number variation (CNV).

Implications of gene copy-number variation in health and diseases

“…A common CNV in LPA gene on chromosome 6, which encodes for atherogenic apolipoprotein (a), which is the primary determinant of the plasma lipoprotein is a risk factor for atherosclerosis. 52,53 Apart from this CNVs were also found to be associated with the lipoprotein disorders. It was found that the low-density lipoprotein receptor gene (LDLR) is found to be affected in the patients with familial hypercholesterolemia.…”

Structural Variablity of Leucocyte Genome and Arterial Cells in Human Atherosclerosis

“…Работы, описывающие вклад CNV в риск развития атеросклероза и его осложнений, немногочисленны и противоречивы [37][38][39][40][41]. В данных исследованиях проводилось тестирование только одной ткани -лейкоцитов периферической крови.…”

Rapid aneuploidy detection or karyotyping? Ethical reflection

“…At present, only common SNPs are found, as the technique cannot detect rare ones. It is also starting to become clear that structural variation, such as variation in location and variations in the number of copies of genes (copy number variation, CNV) plays an important part in someone's risk of disease [97][98][99][100] , which depends on the combination of different SNPs. Much research is still needed before these general genetic profiles can add anything to the existing possibilities of early detection and prevention of disease.…”