An Introduction To Clinical Human Genetics PDF

An Introduction To Clinical Human Genetics LINA KURDAHI BADR, RN, PHD, CPNP, FAAN  Objectives for Today…  The leaner will understand :  Background of genetics/genomics  History of discoveries  Definitions  Brief review of common syndromes.  What you need to know for your practice an...

An Introduction To Clinical Human Genetics LINA KURDAHI BADR, RN, PHD, CPNP, FAAN  Objectives for Today…  The leaner will understand :  Background of genetics/genomics  History of discoveries  Definitions  Brief review of common syndromes.  What you need to know for your practice and confidentiality issue  The past and the present Genetic/Genomic research approaches  Implications for practice  Predictions for the future  The field of genetics has changed… In the past … Our primary concern was determining what gene and mutations caused birth defects and diseases (eg Downs ,CF, SCA, PKU) Now… Much of our focus is on more common, complex conditions, and patient outcome related phenotypes and complex ways of looking at genetics/genomics, for example: – Gene  Gene interactions  Environment Discoveries the past 100 years till now  1866: Mendel's research with plants was the first o discover heredity patterns  1900: The ABO blood group system, the first example of a variable human characteristic that was inherited according to the simple rules of Mendel.  1904: chromosomes occur in matched pairs, one inherited from the mother and one from the father.  1952: DNA rather than protein, carries our genetic information.  1953: The double helix structure of DNA.  1968 : The genetic code is cracked and sequencing the first tRNA molecule.  Discoveries the past 100 years till now  1992: Testing embryos, while still in the womb?, for genetic diseases such as cystic fibrosis and haemophilia.  1996: The first cloned animal, Dolly the Sheep.  2000: The full genome sequence of the model organism Drosophila melanogaster (fruit fly) is completed Discoveries the past 100 years till now cont’d  2002: The mouse genome sequence is completed. The mouse genome is 14 per cent smaller than the human genome, but over 99% of the mouse genes is similar to ours.  2003: Human Genome Project is completed and confirms humans have approximately 20,000– 25,000 genes. Took 13 years of work and $ 3 Billion  2009: The first comprehensive analysis of cancer genomes  2016: Higher number of copies of the gene C4 is related to schizophrenia.  Definitions  Genetics: refers to the examination of the sequence of DNA on a single chromosome.  Genomics: refers to the study of all the genes in the human genome together, 23 pairs of chromosomes including their interactions with each other and the environment. Every single cell in the body contains a complete copy of the approximately 3 billion DNA base pairs.  DNA: the molecule that contains the genetic code for all life forms except for a few viruses.  RNA: The molecule that carries out DNA's instructions for making proteins  Pharmacogenomics: is the study of how a person’s genetic makeup affects their response to medications.  Phenotype: is how genetic and environmental influences come together to create an organism’s physical appearance and behavior.  Epigenetics: The study of heritable changes in gene function that occur without a change in the DNA sequence. The external modifications to DNA that turn genes "on" or "off.”  Genome sequencing & genome wide association studies (GWAS) : Asks is a genetic marker related to a disease?.  Gene therapy: Replacing the disease causing faulty gene with a “normal” copy into an individual’s cells. About 4000 diseases are inherited! Normal Chromosomes  Genetic Diseases  The etiology of a genetic disease is a change in DNA structure that alters the expression of a particular gene. A genetic disease may be caused by a single gene change or by chromosomal abnormalities such as the duplication or deletion of a gene segment, or a change that occurs during cellular division.  Genotyping single-nucleotide polymorphisms (SNPs) can show how diseases might be linked to a gene on a specific chromosome. Eg, SNP genotyping has determined that stroke risk is linked to gene variants on chromosomes 9p21.3, 4q25, and 16q22.  Epigenetics example  Epigenetic studies investigate broad areas of functioning and disease, including neurobehavior, neurodevelopment, diabetes, obesity, cancer, and autoimmune, cardiovascular, Alzheimer, and infectious diseases, as well as how environmental signals induce DNA change  Example: The Dutch Hunger Winter in 1944. Six decades after a brief period of intense famine, adults whose mothers were exposed at the wrong time of pregnancy carried the mark of the Dutch Hunger Winter attached to their DNA. The study explains why the children of mothers who suffer through famine during early pregnancy are at heightened risk of diabetes, obesity, and schizophrenia later in life. “  Gene therapy  The goal of gene therapy is to transfer normal genetic material to faulty genetic material  Researchers have made recent progress in therapies for CF, primary immunodeficiencies, Hemophilia, Blindness Parkinson‘s, and others THE BUBBLE BOY (SCID) THEN AND NOW. Kuo CY, Kohn DB (2016) Gene Therapy for the Treatment of Primary Immune Deficiencies. Curr Allergy Asthma Rep. 2016 May;16(5):39. doi: 10.1007/s11882-016-0615-8  Pharmacogenomics  Pharmacogenomics holds the greatest promise to customize treatment based on an individual’s unique drug response. The role of inherited genetic variation in drug response has been studied for more than half a century and research. Example: Codeine, has little effect on as much as 20% of the population, while 2% of people have such a strong reaction that a normal dose can be life-threatening. About 25% of people can’t effectively absorb Plavix, putting them at increased risk for a heart attack or stroke.  Background Statistics  3% of all babies born have a birth defect  20-30%of all infant deaths is due to genetic  disorders  11% of pediatric hospital admissions are for  children with genetic disorder  12% of adult hospital admissions are for genetic  causes  50% of mental retardation has a genetic basis  Child development consists on both genetic components and environmental factors that interact to produce physical biochemical and mental characteristics of the child  Classificaion Genetic diseases can be classified into:  1. Chromosomal aberrations: loss, addition or  structural alteration of chromosome e.g. down  2. Mutation of a gene or genes and that are  distributed in families e.g. cystic fibrosis  3. Multi-factors as disorders resulting from a  complex interaction of both genetic and  environmental factors e.g. diabetes a) Down's syndrome Trisomy 21  CLASSIFICATION BASED ON IQ  MILD IQ = 50-70 ~ 80%  Moderate IQ = 35-50 ~ 10%  Severe IQ = 20-40 ~ 10%  Profound IQ =