1. Disorders and other genetic traits Bio II

2. Chromosomal Inheritance All but one pair of chromosomes in males and females are the same. –Autosomes - Nonsex chromosomes The different pair, sex chromosomes, determines the sex of an individual. –X-linked (sex-linked) is the term used for genes carried on the X chromosome.

3. X-Linked Alleles X-linked alleles have a different pattern of inheritance than alleles on autosomes because the Y chromosome is blank for these alleles. –Inheritance of a Y chromosome cannot offset the inheritance of an X-linked recessive allele.

4. Human X-Linked Disorders Color Blindness –In humans, color vision receptors in the retina are three different classes of cone cells. Only one type of pigment is present in each class of cone cell. –The allele for blue-sensitive is autosomal, but the red- and green-sensitive proteins are on the X chromosome.

5. Color Blindness

6. Human X-Linked Disorders Muscular Dystrophy –Absence of protein dystrophin allows calcium to leak into muscle cells. Hemophilia –Hemophilia A due to lack of clotting factor IX and hemophilia B due to lack of clotting factor VIII.

7. Males show disorder more than females Son cannot inherit disorder from his father X-Linked Recessive Inheritance

8. Human Genetic Disorders Autosome - Any chromosome other than a sex chromosome. –When a genetic disorder is autosomal dominant, an individual with AA or Aa has the disorder. –When a genetic disorder is autosomal recessive, only aa individuals have the disorder. Carriers - Individuals unaffected by a disorder but can have an affected child.

9. Autosomal Recessive Disorders Tay-Sachs Disease –Progressive deterioration of psychomotor functions. Cystic Fibrosis –Mucus in bronchial tubes and pancreatic ducts is particularly thick and viscous. Phenylketonuria –Lack enzyme for normal metabolism of phenylalanine.

10. Clinical Features Cystic fibrosis is a heterogeneous recessive genetic disorder with features that reflect mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Classic cystic fibrosis is characterized by chronic bacterial infection of the airways and sinuses, fat maldigestion due to pancreatic exocrine insufficiency, infertility in males due to obstructive azoospermia, and elevated concentrations of chloride in sweat. Patients with nonclassic cystic fibrosis have at least one copy of a mutant gene that confers partial function of the CFTR protein, and such patients usually have no overt signs of maldigestion because some pancreatic exocrine function is preserved.

11. Treatment Gastrointestinal Treatment Modified diet Due to pancreatic disorders, children with CF require a modified diet, including vitamin supplements (vitamins A, D, E, and K) and pancreatic enzymes. Maintaining adequate nutrition is essential. The diet calls for a high-caloric content (twice what is considered normal for the child's age), which is typically low in fat and high in protein. Patients or their caregivers should consult with their health care providers to determine the most appropriate diet. The only way to cure CF would be to use gene therapy to replace the defective gene or to give the patient the normal form of the protein before symptoms cause permanent damage. The major goal in treating CF is to clear the abnormal and excess secretions and control infections in the lungs, and to prevent obstruction in the intestines. For patients with advanced stages of the disease, a lung transplant operation may be necessary. Although treating the symptoms does not cure the disease, it can greatly improve the quality of life for most patients and has, over the years, increased the average life span of CF patients to 30 years.

12. Gene Therapy Gene therapy is the use of normal DNA to "correct" for the damaged genes that cause disease. In the case of CF, gene therapy involves inhaling a spray that delivers normal DNA to the lungs. The goal is to replace the defective CF gene in the lungs to cure CF or slow the progression of the disease.

13. Autosomal Dominant Disorders Neurofibromatosis –Tan or dark spots develop on skin and darken. Small, benign tumors may arise from fibrous nerve coverings. Huntington Disease –Neurological disorder leading to progressive degeneration of brain cells, in turn causing severe muscle spasms and personality disorders.

14. Huntington Disorder Autosomal dominant allele Causes involuntary movements, nervous system deterioration, death Symptoms don’t usually show up until person is past age 30 People often pass allele on before they know they have it

15. Achondroplasia Autosomal dominant allele In homozygous form usually leads to stillbirth Heterozygotes display a type of dwarfism Have short arms and legs relative to other body parts

16. Niemann-Pick Disease Infant symptoms include jaundice, difficult feeding, enlarged abdomen, and pronounced mental retardation.

17. The Disease Condition involving the breakdown and use of fats and cholesterol in the body Harmful amounts of lipids accumulate in the spleen, liver, lungs, bone marrow, and brain Autosomal recessive pattern of inheritance (two copies of the gene must be present) Four variants: A, B, C1, and C2 Clinical feature include: severe liver disease, breathing difficulties, developmental delay, seizures, increased muscle tone, lack of coordination, problems feeding, and inability to move eyes vertically. No treatment

18. 5. HOW CAN GENETIC DISORDERS BE DETECTED?

19. Prenatal Diagnosis Amniocentesis Chorionic villus sampling Fetoscopy All methods have some risks

20. Studying Human Genetics Studying Human Genetics is much more complicated than using other model systems (e.g. Pea Plants) –Humans reproduce slowly, have few offspring, and it is unethical to breed humans for experiments There are many techniques that are used to study human genetics indirectly –Karyotypes –Pedigree analysis –Linkage maps

21. Prenatal Diagnosis Amniocentesis Chorionic villus sampling

25. Karyotype Picture of an individual’s chromosomes Making a Karyotype: –Metaphase chromosomes are fixed and stained –Chromosomes are photographed through microscope –Photograph of chromosomes is cut up and arranged to form karyotype diagram

26. Sex Chromosomes Autosomes Karyotype

30. Pedigree Symbols male female marriage/mating Individual showing trait being studied sex not specified generation I, II, III, IV... offspring in order of birth, from left to right

31. Pedigree Symbols male female marriage/mating Individual showing trait being studied sex not specified generation I, II, III, IV... offspring in order of birth, from left to right

33. Human Genetic Conditions A genetic abnormality is an uncommon or rare trait –E.g. Polydactyly A genetic disorder is an inherited condition that may cause medical problems –E.g. Cystic Fibrosis A syndrome is a set of symptoms that characterize a disorder –E.g. Down Syndome

34. Human Genetic Abnormalities/Disorders Different patterns of inheritance are observed depending on the condition: –Autosomal Recessive Inheritance –Autosomal Dominant Inheritance –X-linked inheritance

35. Autosomal Recessive Inheritance If parents are both heterozygous, child will have a 25% chance of being affected