The History and Impact of Genetics in Medicine

1. Session 1 Medical Genetics The History and Impact of Genetics in Medicine

3. What is Medical Genetics? • The specialty of medicine that involves the diagnosis and management of hereditary disorders • Examples of conditions that fall within the scope of medical genetics include: • birth defects and dysmorphology • mental retardation • mitochondrial disorders • cancer genetics • Teratogens • prenatal diagnosis …

4. What is Medical Genetics? • Inheritance of disease in families • Mapping of disease genes to specific locations on chromosomes • Analyses of the molecular mechanisms through which gene causes disease • Diagnosis and management of genetic disease (gene therapy) • Genetic counseling

5. The Importance of Genetics in Medicine Genetic diseases make up a large proportion of the total disease Importance of prevention More effective disease treatment

6. A Brief History Early 1800, Inheritance of physical traits

7. A Brief History • Early 1800, Inheritance of physical traits • 1865-1900 Gergor Mendel • The Law of Uniformity • The Law of Segregation • The Law of Independent Assortment

8. A Brief History 1902, Alkaptonuria as the first inborn error of metabolism, Archibald Garrod The chromosome theory of heredity

9. A Brief History 1944 and 1952 , DNA is the molecule that mediates heredity

10. A Brief History 1953, The physical structure of DNA 1956, The correct number of Human Chromosomes 1959, The defect in Down syndrome was discovered

11. A Brief History 1966, The genetic code is cracked 1977, DNA sequencing technology is developed 1986, PCR is developed by KaryMullis

12. A Brief History In 1990, Human Genome Project begun In 2003, Human Genome Project completed, the "post-genomic era" officially begins Advances in molecular genetic methods, Bioinformatics

13. Types of Genetic Disorders Chromosomal Abnormality Single-gene Disorders Multifactorial Disorders Mitochondrial Disorders

14. Chromosomal Abnormality An abnormality of chromosome number or structure. In 1959, Down syndrome is trisomy 21, Other similar discoveries followed rapidly-Klinefelterand Turner syndromes Development of banding techniques in 1970 Microdeletion syndromes FISH and CGH

15. Single-gene Disorders When a certain gene is known to cause a disease, also known as Mendelian The first edition of McKusick's Mendelian Inheritance in Man, published in 1966, listed 1487 traits Now available electronically as Online Mendelian Inheritance in Man (OMIM) www.Omim.org

16. Multifactorial Disorders Are caused by a combination of environmental factors and mutations in multiple genes Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance Include heart disease and diabetes.

17. The Impact of Genetic Disease • Spontaneous Miscarriages • A chromosome abnormality is present in 40% to 50% of all recognized first-trimester pregnancy loss. • Around 5% to 7% of all recognized conceptions are chromosomally abnormal • Newborn Infants • 2% to 3% of neonates have at least one major congenital abnormality, of which at least 50% are caused exclusively or partially by genetic factors • The incidences of chromosome abnormalities and single-gene disorders in neonates are approximately 1 in 200 and 1 in 100 respectively.

18. The Impact of Genetic Disease • Childhood • Genetic disorders account for 50% of all childhood blindness, deafness, and severe learning difficulty. • In developed countries, genetic disorders and congenital malformations together account for 40% to 50% of all childhood deaths. • Adult Life • Between 5% and 10% of common cancers such as those of the breast, colon, and ovary have a strong hereditary component. • It has been estimated that more than 50% of the older adult population in developed countries will have a genetically determined medical problem.