Chapter 21

1. Chapter 21 Congenital and Genetic Disorders

2. Genetic Control • Genetic information stored in chromosomes • 23 pairs in humans • 22 pairs—autosomes • One pair of sex chromosomes—XX or XY • Karyotype • Visual representation of chromosomes arranged in order of size • Used in diagnosis of chromosomal disorders

3. Examples of Karyotypes

4. Genetic Control (Cont.) • Genotype • Actual genetic information carried by the individual • All cells except the gametes of an individual have the same genotype. • Not all genes are expressed in all cells. • Phenotype • Expression of genes • Appearance of the individual’s characteristics

5. Congenital Disorders • Disorders present at birth • Include inherited or developmental disorders • Inherited disorders may be caused by • Single-gene expression • Chromosomal defect • Polygenic expression • Single-gene disorders • Trait controlled by one set of alleles • Transmitted to subsequent generations

6. Congenital Disorders (Cont.) • Chromosomal anomalies • Usually caused by an error during meiosis • Nondisjunction • Translocation

7. Congenital Disorders (Cont.) • Teratogenic agents • Agents that cause damage during embryonic or fetal development • Multifactorial disorders • Large number of disorders are of this type • Often have pattern of familial inheritance • Environmental component

8. Congenital Disorders (Cont.) • Other congenital or developmental disorders • Result from premature birth • Difficult labor and delivery • Cerebral palsy is an example.

9. Single-Gene Disorders • Classified by inheritance patterns • Recessive • Dominant • X-linked recessive • Single gene controls a specific function • Example: color blindness • May have systemic effects • Examples: cystic fibrosis, Tay-Sachs disease, phenylketonuria (PKU)

10. Single-Gene Disorders • Autosomal dominant disorders • Adult polycystic kidney disease • Huntington’s chorea • Familial hypercholesterolemia • Marfan’s syndrome

11. Autosomal Recessive Disorders • Both parents must pass on the allele for disorder. • Parents may be heterozygous and unaffected; they are termed carriers. • Parents may be homozygous and affected. • Male and female children are affected equally. • Homozygous recessive child has the disorder. • Heterozygous child • No clinical signs of disease • Child is a carrier

12. Autosomal Recessive Disorders (Punnett Square) (Cont.)

13. Autosomal Recessive Disorders (Cont.) • Cystic fibrosis • PKU • Tay-Sachs disease

14. Autosomal Dominant Disorders • Inheritance of one allele causes disorder; only one parent needs to carry allele • No carriers • Unaffected persons do not transmit the disorder. • Some conditions become evident later in life. • Allele for disorder may have been passed on to next generation before diagnosis of disease in parent. • Termed delayed lethal genotype

15. Autosomal Dominant Disorders (Punnett Square) (Cont.)

16. Autosomal Dominant Disorders (Cont.) • Adult polycystic kidney disease • Huntington’s disease • Familial hypercholesterolemia • Marfan’s syndrome

17. X-Linked Disorders • Recessive • Allele carried on the X chromosome but not the Y chromosome • Manifested in heterozygous males lacking the matching unaffected gene on the Y chromosome • Heterozygous females are carriers. • Homozygous recessive females may be affected. • Inheritance may appear to skip generations. • Examples: • Duchenne muscular dystrophy • Classic hemophilia

18. X-Linked Recessive Disorder(Punnett Square)

19. X-Linked Disorders (Cont.) • Dominant disorder • Heterozygous males and females affected • Reduced penetrance in females • Fragile X syndrome is an example. • Most common genetic cause of cognitive deficits • Effects are variable and related to the extent of mutation of the allele.

20. Single-Gene Disorders • Autosomal recessive disorders • Cystic fibrosis • Phenylketonuria • Sickle cell anemia • Tay-Sachs disease • X-linked dominant disorders • Fragile X syndrome • X-linked recessive disorders • Color blindness • Duchenne muscular dystrophy • Hemophilia A

21. Chromosomal Disorders • Down syndrome • Trisomy 21 • May be caused by nondisjunction or translocation • Turner syndrome XO • Affects females • Short stature • Infertility • Klinefelter syndrome XXY • Extra X chromosome is present • Infertility

22. Down Syndrome • Trisomy 21 • Common chromosomal disorder • Affects physical and mental development • Risk increases with maternal age • Triple or quad screening test and/or first-trimester screening test (ultrasound + maternal blood screening) • May be used to screen for risk of Down syndrome • Amniocentesis or chorionic villi sampling used to confirm the disorder prior to birth

23. Characteristics of Down Syndrome • Small head, round face, flat facial profile • Slanted eyes and epicanthic fold • Large tongue, high-arched palate • Small hands, single palmar crease • Short stature • Muscles tend to be hypotonic; loose joints • Delayed developmental stages • Cognitive impairment ranges from mild to major • Delayed or incomplete sexual development • Males infertile • Females have lower rate of conception

24. Down Syndrome (Cont.)

25. Down Syndrome (Cont.)

26. Multifactorial Disorders • Genetic influences combined with environmental factors • Examples: • Cleft palate • Congenital hip dislocation • Congenital heart disease • Type 2 diabetes mellitus

27. Developmental Disorders • Exposure to drugs, chemicals, or radiation during childbearing years • TORCH—acronym for maternal infections that can result in anomalies • Routine prenatal screening tests • Exposure to known teratogens in the first 2 months of development • Impairs organogenesis

28. Effects of Teratogens During Pregnancy

29. Diagnostic Tools • Testing may be available. • Prior to conception • During first trimester of pregnancy • In newborn • Testing recommended for: • Family history of a specific disease • Previous birth to child with abnormality • Ethnic groups with high risk for specific disease • Pregnant women > 35 years of age

30. Diagnostic Tools (Cont.) • Blood tests of pregnant woman • Alpha-fetoprotein testing • In utero testing • Amniocentesis • Chorionic villi assay • Neonatal testing • Excreted metabolites (e.g., PKU) • Blood testing

31. Genetic Engineering • Isolating, copying, and transplanting genes • In microorganisms, plants, animals, humans • Used in agriculture to produce transgenic or genetically modified foods • Ultimate goal • Insert normally functioning allele to prevent disease • Technically possible but clinical trials have not been uniformly successful

32. Gene Therapy • Identifies gene and protein responsible for condition • Determines how gene expression is controlled • Produces drug that will inhibit gene expression • Research focus on cancer growth promoters has resulted in these types of drugs.

33. Genetic Screening and DNA Testing • Screening at-risk populations for a specific allele • Costly • Concerns regarding privacy and access to information • DNA testing to identify individuals for paternity or forensic purposes • Legislation has been drafted in the United States to protect the genetic rights of individuals. • Health care • Employment • Insurance

34. Designer Drugs • Proteomics research • Gene expression • Characterization of proteins significant in the metabolic pathway for expression of a particular allele • Some designer drugs act differently in genetically different individuals. • This research will help develop drugs tailored to an individual’s genotype. • Reduce unwanted side effects of commonly used medications