**2. Genetic variation in the study of human disease**

The potential of genetic discoveries in unraveling pathophysiological mechanisms and identifying drug targets is widely accepted [7]. The sequence of any two individuals is 99.5% identical, and the genomes of any two individuals differ by approximately 0.1% or less. It is in this tiny fraction of the genome that researchers seek to find the collection of sequence variations that determine susceptibility to disease and its outcome. A resource for cataloging the differences between any two genomes was created with the completion of mapping and sequencing of human genome. Sites in the DNA sequence where individuals differ at a single DNA base are called singlenucleotide polymorphisms (SNPs). As some SNPs predispose individuals to have a certain disease or trait or react to a drug in a different way, they are highly useful in diagnostics and drug development. Single-nucleotide polymorphisms (SNPs) have the potential to improve personalized medicine, and discovery of new SNPS enhance the risk stratification of patients with multifactorial diseases. In a clinical setting, SNP testing is particularly useful in complementing family history and phenotypic risk factors. The basic assumption here is that the affected individuals harbor a significant excess of clinically defined established pathogenic DNA variants as compared with a group of unaffected persons (controls) that are available from large datasets obtained from the general population.

The association of an SNP with a disease in an individual can be studied either directly or indirectly. Searching the entire genome for SNPs for disease association

### *An Overview of Gene Variants of Endothelin-1: A Critical Regulator of Endothelial Dysfunction DOI: http://dx.doi.org/10.5772/intechopen.108108*

would be very expensive because it would involve the cost of sequencing the entire genome of several healthy and diseased individuals and comparing the sequences to identify the variants. In the indirect approach, marker SNPs called the "tag SNPs" which represent sets of nearby SNPs on the same chromosome inherited in blocks, and their disease associations are identified. The pattern of SNPs on a block is a haplotype, and a few SNPs are enough to uniquely identify the haplotypes in a block. The HapMap is a map of these haplotype blocks, and the tag SNPs are the specific SNPs that identify the haplotypes. The HapMap reduces the number of SNPs to be scanned in the genome making the indirect approach more efficient and comprehensive.

Using just the tag SNPs, particular regions of chromosomes can be identified that have different haplotype distributions in the two groups of people, those with a disease and those without. The identified regions are scanned in more detail to discover the gene variants in the region that contribute to the disease or determine the response to drugs by affecting drug metabolism pathways, leading to development of more effective tests and interventions.

The 1000 Genomes project was undertaken to provide a comprehensive description of common genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. In this project, genomes of 2504 individuals from 26 populations were reconstructed by sequencing and 88 million SNPs were genotyped. The resource generated provides insights into processes that shape genetic diversity and advanced understanding of disease biology (The 1000 Genomes project Consortium, Nature 2015 [8]).
