1. PEDIGREE ANALYSIS CHAPTER 11 P. 308

2. PEDIGREE ANALYSIS In humans, pedigree analysis is an important tool for studying inherited diseases Pedigree analysis uses family trees and information about affected individuals to:  figure out the genetic basis of a disease or trait from its inheritance pattern  predict the risk of disease in future offspring in a family (genetic counseling)

3. PEDIGREE ANALYSIS Normal Female Normal Male Mating1st born Siblings Affected I II

4. How to read pedigrees Basic patterns of inheritance  autosomal, recessive  autosomal, dominant  X-linked, recessive  X-linked, dominant (very rare)

5. AUTOSOMAL RECESSIVE Trait is rare in pedigree Trait often skips generations (hidden in heterozygous carriers) Trait affects males and females equally  For each of these, overdominance (heterozygote superiority) has been suggested as a factor in maintaining the disease alleles at high frequency in some populations

6. Most common Autosomal Recessive disorders  Cystic fibrosis  Sickle cell anemia  Phenylketonuria (PKU)  Tay-Sachs disease

7. AUTOSOMAL RECESSIVE

9. AUTOSOMAL DOMINANT Trait is common in the pedigree Trait is found in every generation Affected individuals transmit the trait to approximately 1/2 of their children (regardless of sex)

10. AUTOSOMAL DOMINANT

11. ex. achondroplasia (a sketelal disorder causing dwarfism)

12. X-LINKED RECESSIVE Trait is rare in pedigree Trait skips generations Affected fathers DO NOT pass to their sons, Males are more often affected than females

13. X-LINKED RECESSIVE

14. X-LINKED DOMINANT Trait is common in pedigree Affected fathers pass to ALL of their daughters Males and females are equally likely to be affected

15. X-LINKED DOMINANT

16. X-linked dominant diseases are extremely unusual Often, they are lethal (before birth) in males and only seen in females ex. incontinentia pigmenti (skin lesions) ex. X-linked rickets (bone lesions)

17. Remember:  dominant traits may be rare in population  recessive traits may be common in population  alleles may come into the pedigree from 2 sources  mutation happens  often traits are more complex  affected by environment & other genes  Scientists study twins to view/separate environmental contributions vs. environmental factors.  There is a large difference between fraternal twins and identical twins owing to genetic influence  EPIGENETICS OF TWINS EPIGENETICS OF TWINS

18. BELOW ARE SOME PRACTICE EXAMPLES!

19. IF TWO AFFECTED PARENTS HAVE AN UNAFFECTED KID, RECESSIVENESS* CAN BE RULED OUT * both autosomal and x-linked

20. GENETIC COUNSELING A woman’s brother died from Tay Sach’s Disease (autosomal recessive, lethal), but she is unaffected. What are the chances that she is a carrier of the disease? A.2/3 (67%)B. 1/2 (50%)C. 1/4 (25%) D. 1/6 (17%)E. 1/8 (12.5%)

21. HINT A woman’s brother died from Tay Sach’s Disease (autosomal recessive, lethal), but she is unaffected. What are the chances that she is a carrier of the disease? A.2/3 (67%)B. 1/2 (50%)C. 1/4 (25%) D. 1/6 (17%)E. 1/8 (12.5%)

22. D C A B D d Dd D DdDdd DdDd A.2/3 (67%)B. 1/2 (50%)C. 1/4 (25%) D. 1/6 (17%)E. 1/8 (12.5%) The answer is…

23. PROBLEM 2 ASSUMING YOUR GRANDFATHER IS A CARRIER (HETEROZYGOTE) FOR A RARE RECESSIVE, DISEASE CAUSING ALLELE OF A GIVEN GENE, WHAT’S THE CHANCE THAT YOU ARE ALSO A CARRIER OF THIS ALLELE? ©2001 Lee Bardwell

24. you D E F G H IF THEN? A.2/3 B. 1/2 C. 1/4 D. 1/6 E.1/8

25. 1/2 (50% chance) mom got the allele 1/2 (50% chance) she gave it to you if she had it 1/2 x 1/2 = 1/4 = Chance that you got a given allele from Grandpa D D E F G H

26. PROBLEM 3 YOUR GRANDFATHER’S SISTER HAD CYSTIC FIBROSIS (RARE, AUTOSOMAL RECESSIVE). THAT’S THE ONLY CASE IN YOUR FAMILY. (A) WHAT’S THE CHANCE THAT YOU ARE A CARRIER OF CF? A.2/3 B. 1/2 C. 1/4 D. 1/6 E.1/8

27. you D E F G C H A B Your grandfather’s sister had CF but he, his parents, and his descendants are unaffected, as are those who married into the family A. 2/3 B. 1/2 C. 1/4 D. 1/6 E. 1/8

28. you D E F G C H A B D d Dd D DdDdd DdDd 2/3

29. you D E F G H IF THEN?

30. ANSWERS A. 1/4 = Chance that you got any particular allele from from grandpa B. 1/6 = correct answer = 1/4 (see A) x 2/3 (chances that grandpa was a carrier)