Genetic disorders can be divided in two main groups. Mendelian disorders, and then the complex disorders. So Mendelian disorders are monogenic one, disorders with a very strong genetic component. It's up to 100%. And for most of these disorders, one or two alleles is sufficient and enough to develop the disease. Complex disorders or in other word is multifactorial, is an interplay between genes, and then several genes, not one, and also the environmental factors. So the genetic influence is way weaker compared to the Mendelian disorders. And also, the variants in the genes are not sufficient and not enough to develop the complex disorders. So this week, we're talking about the Mendelian disorders. And next week, we will hear from Yuri and Leonard about the complex ones. So named Mendelian disorders, came from the type of inheritance in humans. In 1902, British physician, Archibald Garrod, published his observation on alkaptonuria. He made a link between Mendelian type of inheritance and specific medical condition. So he deduced that the alkaptonuria was inherited in a recessive manner. Mendelian disorders such as, for example, cystic fibrosis, sickle-cell anemia, Duchenne muscular dystrophy, Huntington's disease, each of them are quite rare in a population. However, if we take as a cumulative amount of them, they account in approximately 0.4 percent of all life birth. And if we add to that also congenital abnormalities, it will result in approximately eight percent of the cases of the live birth, which have a genetic disorders recognizable by early adulthood. It's results in up to 8 million children every year, born with a genetic condition. It's of course, cause economical burden, social burden, a personal burden for the families. And what we would like to do is to find the genes underlying these disorders in order to try to improve the diagnostic treatment of these conditions. Before we go further with the story, let me remind you of some terms. It's a genotype, allele, haplotype, and then the phenotype. So let's assume we have two loci, A and B, which are laying on a certain chromosome. And the genotype for this loci for A will be A_1 and A_2, and for the B will be B_1, and then B_2. So A_1 and B_1 is laying on one homologous chromosome and we call these two alleles haplotype. And then B_2, and then A_2 are laying on another chromosome and this is also haplotype. So their allelic combination, A_1, B_1, and then A_2, and then B_2, called the haplotype. And haplotype information is also known as a phase. So the results of genotype may be a phenotype. The phenotype of traits may be binary, so the presence or absence or quantitative. Most of the Mendelian disorders are example of the binary traits, like presence or absence of a certain disease, like cystic fibrosis, for example. Mendelian disorders do run in families and most of the time have a predictable and recognizable inheritance pattern. If we talk about Mendelian disorders, we may talk about the type of inheritance like autosomal dominant and recessive, and then sex-linked. So what does it mean? Autosomal dominant, meaning that the loci and the variant which is causing the disease is laying on autosomes, and one allele is sufficient and enough to develop the disease. We talk about recessive type of inheritance, autosomal recessive type of inheritance, when two alleles, which are laying on one of the autosomes is sufficient and enough to develop the disease. If the causative alleles are laying on X or Y chromosome, we talk about sex-linked type of inheritance. And pedigree analysis of especially large families with many affected individuals are very helpful to understand and to recognize inheritance pattern. As an example of different inheritance patterns, for example, cystic fibrosis, is inherited in autosomal recessive manner. Myotonic dystrophy type one is autosomal dominant. And the examples of the sex-linked type of inheritance is, for example, hemophilia A and muscular dystrophy Duchenne, which are inherited in X-linked recessive type. And Rett syndrome is an example of X-linked dominant. So to recognize Mendelian disorders and to assume the genetic influence, we may, by studying the families. Usually, it's increased frequency of the phenotype, disease in this case, in the close relatives. Also, it's increased frequency of the disease in a certain population. And also, to study the genetic influence, we may use a concordance between the monozygotic and the dizygotic twins. There is a database which called OMIM, Online Mendelian Inheritance in Men. It's online database which has been established in 1997 by Victor McKusick and that is focused on inherited genetic conditions in humans. So currently, it's more than seven and a half thousand conditions which are listed there, and this number is not static. So approximately, 300 entities are added every year, and there is an opinion that this amount is actually underestimated. So in reality, there is much more Mendelian conditions which we don't know yet. So if we look at this database, more than 3,000 genes has been identified, underlying more than 4,000 Mendelian diseases. The question is, how these genes has been found and how we will and may identify the new genes? So we will spend the next four videos talking about approaches which are used and currently in use to study the Mendelian conditions.