Genetics: Past, Present, and Future Robert M. Fineman, M.D., Ph.D. Web siteWeb site

Genetics is that branch of biology that deals with heredity and variation.

Genotype: the genetic constitution of an individual as applied to a single locus or all the loci collectively; when applied to the entire genetic constitution, it is synonymous with genome.

Alleles: different forms of a gene at the same locus on homologous chromosomes.

Phenotype: the appearance or observable nature of an individual; the visible effects of the interaction of the genotype and the environment.

Medical Genetics: the science or study of biological variation as it pertains to health and disease in humans.

Clinical Genetics or Genetic Medicine (also known now as Genomic Medicine): that part of medical genetics concerned with health and disease in individuals and families.

Public Health Genetics: the use of genetic information and technology to promote, protect and, thereby, improve the public’s health and well-being.

Genetic Screening: the use of various methods or techniques to evaluate populations or groups of individuals independent of a family history of a disorder, and without clinical signs or symptoms.

Genetic Testing: the use of various methods or assays to determine the genetic status of an individual already suspected to be at high risk for a particular genetic condition because of a relevant family history, clinical signs or symptoms, or a positive screening test result.

Genetic Variation There is no such thing as THE human genome sequence. There is about a 3 million bp difference between any two non-related individuals. Common variant sequences (alleles) occur every 1/1000-1/1500 bp. There are an estimated 2-3 common variants per gene (on average).

DNA Mutations Nonsense Missense Frameshift Regulatory RNA splicing Expanding trinucleotide repeats Others

Our Challenge Is One Of Change Genetics in the Past Human Genome Project/Related Technologies New Genetics/Genomics Genomic Medicine Genomic Medicine and Research Genomics and Society

Medical Genetics Timeline 1950s: Clinical and mathematical genetics 1960s: Cytogenetics, biochemical genetics, genetic nosology, dysmorphology, NBS 1970s: Prenatal screening/dx, genetic counseling, molecular diagnosis 1980s: Early genomics, biotechnology

The Genetics Center Is A Resource For The Entire Community Preconception: Care/Data/Education Prenatal: Care/Data/Education Infant/Childhood: Care/Data/Education Adolescent/Adult: Care/Data/Education Usually Involves Other Health and Social Services Professionals

Medical Genetics Timeline 1990s: Computers; Internet; genetic informatics; genetics of complex diseases; molecular medicine; ethical, social and legal issues; commercialization and de- academization; consumerization

Genetics in the Past Conditions caused by an extra or missing chromosome or part of a chromosome Conditions caused by a mutation in a single gene or in a mitochondria

Genetics in the Past These conditions: are important to the individuals and families who have them are relatively rare, even when added together do not affect most people play a small role in health care and society

Genetics in the Past These conditions are rare enough such that genetic services could be provided by genetic health care professionals, with occasional involvement of primary care professionals and other specialists.

Genetics in the Past Regarding research: because of their relatively small impact on the health of our nation, these conditions were of limited interest only very recently did genetics begin to help answer basic health care questions

Types and Frequencies of Genetic Diseases Type Chromosomal Single Gene Multifactorial (Emory & Rimoin, 1997) Lifetime Frequency 3.8/ / /1000

Of the ten leading causes of death in the U.S., nine are causally related, in part, to genetic/genomic factors (CDC, 1997). Heart Disease (31.0%) Cancer (23.2%) Stroke (6.8%) COPD (4.8%) Injury (4.2%) (? genetic) Pneumonia/Influenza (3.9%) Diabetes (2.8%) Suicide (1.3%) Kidney Disease (1.1%) Chronic Liver Disease (1.1%)

Of the ten leading causes of death worldwide, nine are causally related, in part, to genetic/genomic factors (CDC). Heart Disease (13.7%) Stroke (9.5%) Pneumonia (6.4%) HIV/AIDS (4.2%) COPD (4.2%) Diarrhea (4.1%) Perinatal (4.0%) TB (2.8%) Tracheal/Bronchial/Lung Cancer (2.3%) Traffic Accidents (2.2%) (? genetic)

Unfortunately, more than 50% of premature death and disability in the United States is caused by things people do to themselves or to others, e.g., smoking, diet and exercise, alcohol and drugs, violence, etc.

The new genetics (or genomics) comes largely from knowledge derived from the Human Genome Project and related technologies.