Cindy Boer

General Introduction | 17 1.1 ▲ Figure 3: The central Dogma of Molecular Biology DNA can be copied into DNA or translated into RNA, RNA can be copied into RNA or translated into protein. A) Schematic representation of the molec- ular dogma, depected as nucelotide letters or as an schematic image. B) Representation of the possible effect of a single nucelotide variant on protein translation, due to the SNV the protein triplet code does not code for the amino acid Asparagine (N) but for Lysine(K), a nonsynonymous SNV, as the SNV changes the protein code. A synonymous SNV does effect DNA and RNA sequence but not the protein amino acid sequence. However, SNVs that have a large effect on the functioning of a gene can impact reproductive success and will not propagate into a population, and thus will occur in- frequent in a population (<1%). Common SNVs, those that occur frequently in a pop- ulation(>1%), have usually relatively small effects, and, thus, are under less selective pressure[34] . Certain SNVs in relative proximity tend to always co-occur together, they are said to be in linkage disequilibrium (LD). Such a group of SNVs is called a haplotype, and, as with individual SNVs, different haplotypes occur at different frequencies in dif- ferent human populations, and they will differ more in frequency if the populations are geographically and ancestrally more different[35] Complex genetics Since genetic variation can explain differences in disease risk between individuals, in- vestigating which and how specific genetic variations can increase or decrease disease risk could provide insight into the disease pathology. In order to identify which genetic variation is related to a disease, several approaches have been tried, including linkage analysis in families or sib-pairs and, genome wide association studies (GWAS). Gregor Johan Mendel was the first to demonstrate that traits can be inherited from parent to offspring in his plea plant ( Pisum sativum ) experiments in 1865[36]. With his experiments he laid the foundation for the field of genetics. However, it was not until the 20th century that his work was rediscovered and, it took until 1941 that Stecher et al. , first postulated the possible involvement of genetics in osteoarthritis. He first described that the Herben’s nodes (bony nodes on the joints) seen in hand osteo-