Classification of Genetic Disorders This PowerPoint file contains a number of slides that may be useful for teaching of genetics concepts. You may use these slides and their contents for non-commercial educational purposes.

Fig. 13.3 ©Scion Publishing Ltd Etiology of diseases. For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle. Fig. 13.3 ©Scion Publishing Ltd

Classification of genetic disorders + environment Multifactorial Single gene Chromosomal Mitochondrial Somatic mutations (cancer) Male

Fig. 1.15 ©Scion Publishing Ltd Continuum of penetrance. There is a continuum of penetrance from fully penetrant conditions, where other genes and environmental factors have no effect, through to low-penetrance genes that simply play a small part, along with other genetic and environmental factors, in determining a person’s susceptibility to a disease. Multiple sclerosis is used as an example of a multifactorial condition where genetic factors play a major part in determining susceptibility, but current research suggests that each individual factor has a very low penetrance. Fig. 1.15 ©Scion Publishing Ltd

Genetic factors Male Mutations in single genes (often causing loss of function) Variants in genes causing alteration of function Chromosomal imbalance causes alteration in gene dosage

Classification of genetic disorders Single Gene Disorders Male Mutations in single genes Multifactorial diseases + environment Variants in genes Chromosome disorders Chromosomal imbalance

Heterozygotes with one copy of the altered gene are affected Dominant Heterozygotes with one copy of the altered gene are affected Recessive Homozygotes with two copies of the altered gene are affected Male X-linked recessive Males with one copy of the altered gene on the X-chromosome are affected

Genetic disorders Multifactorial (common) - “Environmental” influences act on a genetic predisposition to produce a liability to a disease. - One organ system affected. - Person affected if liability above a threshold. Single gene (1% liveborn) - Dominant/recessive pedigree patterns (Mendelian inheritance). - Can affect structural proteins, enzymes, receptors, transcription factors. Chromosomal (0.6% liveborn) - Thousands of genes may be involved. - Multiple organ systems affected at multiple stages in gestation. - Usually de novo (trisomies, deletions, duplications) but can be inherited (translocations).

The contributions of genetic and environmental factors to human diseases GENETIC ENVIRONMENTAL Duchenne muscular dystrophy Haemophilia Osteogenesis imperfecta Club foot Pyloric stenosis Dislocation of hip Peptic ulcer Diabetes Tuberculosis Phenylketonuria Galactosaemia Spina bifida Ischaemic heart disease Ankylosing spondylitis Scurvy Rare Genetics simple Unifactorial High recurrence rate Common Genetics complex Multifactorial Low recurrence rate

Multifactorial “Environmental” influences act on a genetic predisposition One organ system affected Single gene Dominant/recessive pedigree patterns Structural proteins, enzymes, receptors, transcription factors Chromosomal Multiple organ systems affected Inherited or de novo Environmental Drugs, infections

Single gene disorders High risks to relatives Dominant/recessive pedigree patterns Some isolated cases due to new dominant mutations Structural proteins, enzymes, receptors, transcription factors I:1 AA I:2 AB II:1 II:2 II:3 BB ? III:1 Tom I:1 I:2 II:1 II:2 II:3 II:5 II:6 II:8 III:1 III:2 IV:1 I:2 I:1 I:3 II:1 II:2 II:3 II:4 II:5 II:6 II:7 II:8 II:9 II:10 II:11 II:12 II:13 II:14 II:15 III:1 III:2 III:3 IV:1 IV:2 IV:3 IV:4 III:4 III:5 IV:5 IV:6 IV:7 III:6 III:7 IV:8 IV:9 IV:10 III:8 III:9 III:10 III:11 III:12 III:14 III:13 III:15 III:16 III:17 IV:11 IV:12 IV:13