Genetics Infographic PDF

INTRODUCTION TO GENETICS WHAT IS YOUR GENOME? Your genome can be thought of as a book that contains the instructions to life. Chromosomes are the chapters in this book....

INTRODUCTION TO GENETICS WHAT IS YOUR GENOME? Your genome can be thought of as a book that contains the instructions to life. Chromosomes are the chapters in this book. DNA are the words written across the pages. The 3,000,000,000 units of DNA that make up your genome are CELL packaged into 23 pairs of chromosomes and exist in every cell of your body WHAT ARE GENES & WHAT DO THEY DO? T A G C T G ATGTAGG C G T A C A DNA A A C G A C TACATCC G G A T G A Genes are important paragraphs interspersed throughout the book and only makeup 1.5% of T A G C T G ATGTAGG C G T A C A your genome. You have20,000 – 25,000 RNA genes. Genes contain information for human traits and Protein the biological building blocks for your cells. To make these building blocks, your body makes a photocopy of the required paragraphs, generating a copy of the gene called RNA The RNA,is then used by your body to make your biological building blocks called proteins. These resources have been developed by the International Alliance of ALS/MND Associations. The material has been adapted by Kristiana Salmon and Helmut Bernhard from a presentation given by Dr. Kelly Williams, Macquarie University, Australia  INTRODUCTION TO GENETICS WHAT IS GENETIC VARIATION? Protein These are considered different “versions” of the genes, and give us our unique traits as humans. AACTGC TGCCCAGGCAGAT When your DNA is copied, mistakes can happen and this is a normal process. Single nucleotide When a mistake in your DNA occurs, and results variant A A C T G C T A C A T A G G C A G A T in a detrimental outcome such as a disorder, this is called a mutation or pathogenic variant. Your DNA is made up of individual units. There are 4 types of DNA units: A, T, C, and G. These detrimental mistakes can be caused by a change in your DNA units (such as a single Everyone has the same genes, but a gene can nucleotide variant), a portion of your DNA be spelled out slightly differently in different deleted or inserted, or a small region of DNA individuals, due to genetic variation. units repeated multiple times. HOW ARE GENES INHERITED? Chromosome You have 46 chromosomes in which your DNA is packaged. You inherited one set of 23 chromosomes from your mother, and the Gene remaining set of 23 chromosomes from your father. Depending on which version of a gene you inherited from each parent, the gene will result in a different trait. HOW DO WE INHERIT GENETIC DISORDERS? Some genetic disorders only need one copy of a Autosomal Dominant Autosomal Recessive mutant version of the gene to be present for an affected unaffected carrier carrier individual to be affected by the disorder. This is called autosomal dominant inheritance. Some genetic disorders need two copies of a mutant version of the gene to be present for an individual to be affected by the disorder. This is called autosomal recessive inheritance. affected affected unaffected unaffected carrier affected unaffected carrier Some people have a copy of a mutant version of the gene, but are unaffected by the disorder. The mutant version of the gene can be passed on, and such people are called carriers. These resources have been developed by the International Alliance of ALS/MND Associations. The material has been adapted by Kristiana Salmon and Helmut Bernhard from a presentation given by Dr. Kelly Williams, Macquarie University, Australia  ALS/MND GENETICS WHY IS IT IMPORTANT TO UNDERSTAND GENETIC CAUSES OF DISEASE? A pedigree chart displays a family tree, and Pedigree analysis, combined with DNA Help with diagnosis shows the members of the family who are samples from family members, can help affected or unaffected by a genetic trait. with discovery of new genes. Understand disease biology Target for treatments affected unaffected affected unaffected male male female female WHY IS GENETICS RELEVANT TO ALS/MND? Most people with ALS/MND develop the condition for unknown reasons. Some people with ALS/MND have a family history of the condition, or related disorders. Historically, the above have been referred to as sporadic and familial ALS/MND, respectively. Genetic causes have not been identified in all people with familial ALS/MND. In some cases of sporadic ALS/MND, genetic causes have been identified. Familial/hereditary Ambiguous Sporadic with Sporadic family history genetic mutation Family history is unclear. A genetic cause has been Underlying genetic cause identified, but there is no with reduced penetrance family history. In these families, it is likely that a gene causing disease has been (see Advanced Concepts identified as the cause. in ALS/MND Genetics) There is no family history, and a genetic cause has not been identified. Our understanding of the role genetics plays in ALS/MND has advanced considerably. The field is moving away from a clear distinction between familial and sporadic ALS/MND, recognizing that ALS/MND exhibits a spectrum of inheritance patterns and genetic involvement. More than 40 genes have been identified as being associated with either causing or increasing the risk of developing ALS/MND. Incidence of these genetic mutations varies geographically. These resources have been developed by the International Alliance of ALS/MND Associations. The material has been adapted by Kristiana Salmon and Helmut Bernhard from a presentation given by Dr. Kelly Williams, Macquarie University, Australia  ALS/MND GENETICS IF I CARRY AN ALS GENE MUTATION, WILL I DEFINITELY DEVELOP ALS/MND? This is called gene penetrance. Penetrance is the risk that you will develop ALS/MND if you carry an associated gene mutation. Most ALS/MND gene mutations have incomplete penetrance, meaning there is a chance that symptoms may never develop. Both genetic and other factors (environment, lifestyle, ageing) contribute to the development of ALS/MND symptoms. Individuals who all carry the same ALS/MND gene mutation Complete penetrance Incomplete penetrance CAN GENES AFFECT THE TYPE OF ALS/MND? ALS/MND varies between individuals: ALS symptoms FTD symptoms Site of onset of symptoms ALS & FTD symptoms Age of onset Progression rate Impact on cognition Some gene mutations directly cause ALS/MND, and influence the type of symptoms present, while other mutations increase the risk of developing ALS/MND, and modify the symptoms present. Some gene mutations are associated with increased risk of developing other diseases as well, such as frontotemporal dementia (FTD) or ataxia. This is called pleiotropy. These resources have been developed by the International Alliance of ALS/MND Associations. The material has been adapted by Kristiana Salmon and Helmut Bernhard from a presentation given by Dr. Ammar Al-Chalabi, King’s College London, United Kingdom  ALS/MND GENETICS WHAT CAN WE DO ABOUT GENETIC ALS/MND? Therapies are being developed that specifically target ALS/MND-associated genetic mutations. Therapeutic strategies can include: antisense oligonucleotides, antibody therapy, and gene therapy Antisense Oligonucleotide Therapy Normal gene correctly formed protein Accumulation of Mutated gene misfolded protein misfolded protein leads to ALS Mutated gene Blocks formation treated wih ASO of toxic protein Antisense oligonucleotide (ASO) a small piece of synthetic DNA or RNA, designed to bind to a specific gene Antibody Therapy Flags the protein Mutated gene misfolded protein to be eliminated by the body’s natural Antibody targeting immune system misfolded protein Gene Therapy Viral vector with healthy gene Healthy gene + Viral vector These resources have been developed by the International Alliance of ALS/MND Associations. The material has been adapted by Kristiana Salmon and Helmut Bernhard from a presentation given by Dr. Ammar Al-Chalabi, King’s College London, United Kingdom