Multi-factorial Disorders

1. Multi-factorial Disorders Dr Maha Al-Sulaimani Department of Biochemistry College of Sciences

2. Definition • As the name implies, multi-factorial conditions are not caused by a single gene, but rather are a result of interplay between genetic and environmental factors. • Diseases with multi-factorial inheritance are not genetically determined, but rather a genetic mutation may predispose an individual to a disease. Other genetic and environmental factors contribute to whether or not the disease develops.

3. Definition • Genetic disorders may also be complex, multi-factorial, or polygenic, meaning that they are likely associated with the effects of multiple genes in combination with lifestyle and environmental factors. • Multi-factorial disorders include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance.

4. Multi-factorial Disorders - “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.

5. Etiology of diseasesFor any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere within the triangle.

6. Continuum of Penetrance

7. 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.

8. Continuum of Penetrance • Multiple sclerosis is used as an example of a multi-factorial condition where genetic factors play a major part in determining susceptibility, but current research suggests that each individual factor has a very low penetrance.

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

10. Haemophilia Osteogenesis imperfecta Peptic ulcerDiabetes Club footPyloric stenosisDislocation of hip Duchenne muscular dystrophy Tuberculosis Scurvy Spina bifidaIschaemic heart diseaseAnkylosingspondylitis PhenylketonuriaGalactosaemia GENETICENVIRONMENTAL The contributions of genetic and environmental factors to human diseases Rare.Genetics simple.Unifactorial.High recurrence rate. Common.Genetics complex.Multifactorial.Low recurrence rate

11. Quantitative Traits • Multi-factorial disorders are also called quantitative traits. • An example of a polygenic trait is human skin color. Many genes factor into determining a person's natural skin color, so modifying only one of those genes changes the color only slightly.

12. Quantitative Traits • Many disorders with genetic components are polygenic, including most causes of autism, cancer, diabetes and numerous others. • Most phenotypic characteristics are the result of the interaction of multiple genes.

13. Classification • Congenital and Adult Onset. • Examples of congenital disorders: • Congenital heart defects. • Pyloric stenosis(infantile): is a condition that causes severe vomiting in the first few months of life. There is narrowing (stenosis) of the opening from the stomach to the duodenum, due to enlargement (hypertrophy) of the muscle surrounding this opening (the pylorus, meaning "gate"), which spasms when the stomach empties.

14. Classification 3. Talipes: A club foot, or congenital talipes equinovarus (CTEV), is a congenital deformity involving one foot or both. The affected foot appears rotated internally at the ankle.

15. Classification 4. Psoriasis: is an autoimmune disease that appears on the skin. • It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. • Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of stroke, and treating high blood lipid levels may lead to improvement.

16. Classification • Examples of Adult Onset: • Diabetes Mellitus. • Glaucoma. • Cancer (not always). • Mannic Depression (bipolar disorder). • Hypertension.

17. Breast Cancer • Cancer is a leading cause of death worldwide. • It accounted for 7.4 million deaths (around 13% of all deaths) in 2004 (statistics published in 2009).

18. 10 Most Common Cancers among Saudis

19. Breast Cancer • Breast cancer is also widespread in Saudi females. • In the Kingdom of Saudi Arabia, breast cancer constitutes ~24% of all cancers in Saudi women.

20. Risk Factors for Breast Cancer • Female (1% male). • Aging. • Relative (mother or sister). • Menstrual history: • early onset. • late menopause. • Child birth: • After the age of 30.

21. Risk Factors for Breast Cancer • Radiation exposure. • Breast disease: • Atypical Hyperplasia. • Intraductal carcinoma in situ. • Intralobular carcinoma in situ. • Obesity. • Diet: • Fat.

22. Exogenous Estrogen • Hormonal replacement therapy(HRT). • 30% increased risk with long term use . • Oral Contraceptives(OC): • risk is slight. • risk returns to normal once the use of OC’s has been discontinued.

23. Genetics • BRCA-1. • BRCA-2. • P53. • Myc (transcription factor).

24. Obesity • What is obesity? • If a person's bodyweight is at least 20% higher than it should be, he or she is considered obese. • If your Body Mass Index (BMI) is between 25 and 29.9 you are considered overweight. If your BMI is 30 or over you are considered obese.

25. Causes of Obesity • Consuming too many calories. • Leading a sedentary lifestyle. • Endocrine disruptors (fructose). Fructose is mainly metabolized in the liver, the target organ of the metabolic alterations caused by the consumption of this sugar.

26. Causes of Obesity • In a study, rats receiving fructose-containing beverages presented a pathology similar to metabolic syndrome, which in the short term causes lipid accumulation (hypertriglyceridemia) and fatty liver, and eventually leads to hypertension, resistance to insulin, diabetes and obesity.

27. Causes of Obesity 5. Some medicines (antidepressant drugs). 6. Genetic factors (like the leptin receptor).

28. Etiology • Obesity is multifactorial, with genetic, neurologic, behavioral, and occasionally endocrinologic disorders playing a role. • The genetic tendency toward this disease is well-documented. Twin studies reveal a higher rate of obesity within monozygotic twins than within dizygotic twins

29. Etiology • Neurologically, certain lesions in the hypothalamus can provoke hyperphagia and decreased activity, leading to obesity. • There also is evidence linking particular neurotransmitters to satiety or decreased appetite, such as serotonin and catecholamines. • Glucagon also appears to promote satiety, while insulin has been linked to increased appetite.

30. Etiology • Behavioral factors from learned dietary habits as children to the vicious cycle, seen especially in adult-onset obesity, of depression to overeating to excessive weight gain to worsened self image back to depression, and so on.