Future Use of Genomics in Coronary Artery Disease
Samir B. Damani, MD* and
Eric J. Topol, MD, FACC*, ,*
* Division of Cardiovascular Diseases, Scripps Clinic, La Jolla, California
Scripps Genomic Medicine, Scripps Health, and the Scripps Research Institute, La Jolla, California.
View larger version (32K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1 Schematic of Genetic Linkage and Recombination
(A) Two homologous chromosomes: blue (paternal) and orange (maternal). Three genes with separate alleles and linkage disequilibrium "bins" noted (A,a; B,b; C,c; bins 1 to 4). (B) Crossing over during meiosis. (C) Two alleles and their linked bins (C,c; bins 3 and 4) have switched locations via recombination. Four additional alleles and their associated bins (A,a; B,b; bins 1 and 2) have not switched and are considered linked. (D) Recombined haploid chromosomes segregate separately during meiosis as gametes before fertilization. (E) Sample recombination frequencies between genes demonstrating higher rates of recombination for genes further apart.
|
|
View larger version (19K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2 SNPs, Tag SNPs, and Microsatellites as Genomic Markers
(A) Autologous chromosome with evenly spaced microsatellites. (B) Segment of deoxyribonucleic acid (DNA) between microsatellite markers. Single nucleotide polymorphisms (SNPs) are noted (A,B,C...) within the DNA segment. Tag SNPs (C,H,K) travel with other noted SNPs as blocks (haplotypes) and can serve as a surrogate for these haplotypes and, more importantly, disease-causing genes in close proximity. (C) A DNA segment with alternative alleles and genomic markers of the same genes designated in part B of the figure. Note that the microsatellite markers are not as close in proximity to the genes as the noted SNPs.
|
|
View larger version (34K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3 AMD Composite Genomic Risk
Relative risk plotted as a function of the genetic load of the 5 variants that influence risk of age-related macular degeneration (AMD). Two variants are in the CFH gene on chromosome 1: Y402H and rs1410996. Another common variant (A69S) is in the hypothetical gene LOC387715 on chromosome 10. Two relatively rare variants are observed in the C2 and BF genes on chromosome 6. There was no evidence for interaction between any of the variants, suggesting an independent mode of action. Reprinted with permission from Maller et al. (18).
|
|
|
