Milestones of the genetic revolution in particular in relation to human genetics and the implications in medicine;
A. The discovery of the double helix in the 50s of last century
B. The discovery of PCR analysis which enabled DNA analysis of minute quantitie
C. Completion of the human genome project at the beginning of the 21st century that has been the major trigger for the discovery of the various genes comprising the human genome followed by the evaluation of the gene products and function — identification of the RNA and protein products and the understanding of genes activity and control systems.
Milestones in the development of genetic analysis technologies that allowed the research and analysis of the structure and function of our genome. These technologies contributed enormously in deciphering and understanding the role of the various genes and their relationship to human diseases (inherited and non-inherited diseases) as well as other human characteristics;
A. PCR, which enabled a breakthrough in studying genetic material of higher organisms, including humans, in which the presence and availability of DNA is usually only in minute quantities preventing in the past thorough studies of the human genome and its' characterization in contrast to bacteria and viruses.
B. The development of genome sequencing possibilities first by the Sanger technique and further developments of equipment for large quantities sequencing by automated instruments resulting the reduction of the costs of this important technology.
C. Identifying DNA polymorphisms, especially SNP (SINGLE NUCLEOTIDE POLYMORPHISMS) that contribute to the variance among human individuals.
D. The discovery of restriction enzymes as catalysts for the study of the normal genome structure and mutations.
E. Development of sophisticated techniques for the analysis of genome structure variations regarding deletions or insertions, first by FISH analysis and later by the "Genetic chips" = Chromosomal micro-array analysis (CMA) platforms
F. MLPA (Multiplex ligation-dependent amplification) which enables quantitative measurement of gene products in the aim to characterize gene activity in normal and disease status.
G. EXOME –Genome wide sequencing only of the encoded parts of our genome (the exons) to facilitate mutations analysis.
H. NEXT GENERATION SEQUENCING (NGS) which allows extensive genome sequencing analysis, quick, efficient and relatively inexpensive.
These developments have allowed a better understanding of the human body different functions, its complex systems and identification of the disruptions in various medical conditions and disorders and the implication to medicine in better understanding the most meaningful background for the human disorders and better and more accurate means for diagnosis, prevention and treatment of diseases for both the individual as well as for the society at large in public health.
A. Dominant diseases; By identifying the relevant genes and the causative mutations we are able today to characterize the clinical background for the differences in the clinical presentation between these disorders as for the precise cause for variabilities for each of these diseases – gain of function vs. haploinsufficiency, or the reason that some of them show clinical variability or partial penetrance
B. Characterization of the genetic background in multifactorial disorders which are most of the diseases of the adult. By identifying the various genes involved in these diseases and the environmental influences a much better ways are at hand at present to characterize and diagnose the disorders inherited by this complex way of inheritance (e.g. autism, mental retardation, autoimmune diseases, etc.).
C. Understanding the genetic background of recessive diseases, identifying relevant genes, the mutations causing the diseases including in disorders that are more frequent either in the general population or in various ethnic groups, such as the relative frequent disorders among ethnic groups in Israel - Jews and non-Jews (Israeli EDOT or Arab populations). The reasons for the high frequencies of these disorders (Founder, Selection, assortative mating etc.). Programs for the prevention of these diseases by population screening programs either before childbirth or before marriage, screening program aimed for ultra-Orthodox population or Arab populations and the requirement for these programs as outlined by WHO (World Health Organization)
Gene editing – Recent developments in this field by the CAS9- CRISPR technology that allows efficient gene editing and manipulations for the study of gene function and the development of accurate options for the treatment of human diseases.
Cancer genetics; somatic vs germinal mutations (sporadic versus inherited). Breast cancer as an example. The genetic backgrounds for the Causes of cancer – loss of homozygosity (LOH), oncogenes and DNA repair systems – colon cancer – HNPCC as an example. The testing and screening of cancer genes and mutations in Israel for prevention and treatment.
Prenatal diagnosis; amniotic fluid analysis, chorionic villus sampling – CVS, pre-implantation diagnosis – PGD, and recently the option for non-invasive prenatal diagnosis – NIPT (NON INVASIVE PRENATAL TESTING).
Tretament of genetic disorders; Gene therapy, the supplementation of missing proteins such as insulin, growth hormone- GH etc. ,gene editing and inserting genes by the CAS9-CRISPR system.
Regenerative medicine, production of normal tissues and body parts by stem cells including the use of cloning, embryonic stem cells and induced stem cells - iPSC
Pharmacogenetics; individual medicine
The significance and implications of the genetic information for individuals and society.
The basics of bioethics, bioethics principles (nonmaleficence, beneficence, autonomy, and justice); eugenics and its consequences to various societies in the 20th century, genetic determinism, the dangers of withholding digital information of genetic data on the internet and the danger to lose autonomy, the questions of commercialization. (Medicine for the wealthy - individuals and countries), The importance of professional counseling vs. the risk of outlining inaccurate information and non-professional interpretations of the genetic data. Orphan diseases problems and difficulties in raising funds for research of rare disorders, confidentiality, and intimacy as opposed to informing family relatives for potential risks. Testing for minors (recessive disorders carrier status), prenatal diagnosis, what's appropriate and what's less deserving – the dangers of the slippery slope. Diagnostic tests as compared to predictive test results. The importance and dilemma of population screening programs. Diagnosis and treatment of genetic disorders vs. enhancement and improvements of the human capabilities, the question of appropriateness for aiming to obtain "the perfect man"