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Pedigree analysis


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Pedigree analysis

  1. 1. The Inheritance of Single-Gene Differences Human pedigree analysis
  2. 2. Pedigree analysis <ul><li>Analysis of inheritance in human families </li></ul><ul><li>A very important tool for studying human inherited diseases </li></ul><ul><ul><li>Allow inferences concerning genotypes in a family or population </li></ul></ul><ul><ul><li>Allows predictions concerning phenotypes of offspring inheriting a genetic disease (genetic counseling) </li></ul></ul><ul><li>Typically small number of offspring </li></ul><ul><ul><li>Mendelian ratios rarely observed </li></ul></ul><ul><ul><li>this means the normal 3:1 dominant to recessive ratio doesn’t usually occur. </li></ul></ul>
  3. 3. Most common symbols used in creating a pedigree unaffected male unaffected female affected male affected female
  4. 4. Other common signs and symbols used in pedigree analysis
  5. 5. Sample pedigree - cystic fibrosis The roman numerals indicate the generation (I, II or III) and the numbers show birth order of children (1, 2, 3, 4 etc.) female male affected individuals
  6. 6. <ul><li>Describe the pedigree on the previous slide for the following questions: </li></ul><ul><li>What disease or trait is being shown? </li></ul><ul><li>Is person I-1 male or female? </li></ul><ul><li>Has person II-3 mated? </li></ul><ul><li>How many children do I-1 and I-2 have? </li></ul><ul><li>Which individuals in this family have cystic fibrosis? </li></ul><ul><li>Compared to the individuals in generation I, are the individuals in generation III: children, parents, grandchildren or siblings? </li></ul>
  7. 7. Based on the same pedigree, we can determine a reasonable guess as to what the genotypes of the parents and offspring are: <ul><li>Assuming this is a recessive gene, we know that II-3 and III-4 must be “aa.” </li></ul><ul><li>Therefore both parents of these offspring must have given an “a” allele. </li></ul><ul><li>So, I-1, I-2, II-4 and II-5 must each have one “a” in their genotypes. </li></ul><ul><li>Since I-1, I-2, II-4 and II-5 don’t have the disease, their other allele must be “A.” </li></ul><ul><li>All the rest of the people could be either AA or Aa. </li></ul>
  8. 8. I-1 I-2 II-1 II-2 II-3 II-4 II-5 <ul><li>What are the genotypes or possible genotypes for each individual in this family? </li></ul><ul><li>Use the letter B to represent dominant alleles and b to represent recessive alleles. </li></ul>
  9. 9. Categories of inheritance <ul><li>Autosomal means inherited on chromosome 1-22 while sex-linked means inherited on either X or Y chromosome. </li></ul><ul><li>Autosomal recessive </li></ul><ul><ul><li>e.g., PKU, Tay-Sachs, albinism </li></ul></ul><ul><li>Autosomal dominant </li></ul><ul><ul><li>e.g., Huntington’s Disease </li></ul></ul><ul><li>X-linked recessive (meaning this allele is found on only the X chromosome: can be in males or females) </li></ul><ul><ul><li>e.g., color-blindness, hemophilia </li></ul></ul><ul><li>X-linked dominant (meaning this allele is found on X chromosomes; can be in males or females) </li></ul><ul><ul><li>e.g., hypophosphatemia </li></ul></ul><ul><li>Y-linked (meaning the allele is found on the Y chromosome and can only be in males ) </li></ul>
  10. 10. Autosomal recessive traits <ul><li>Trait is rare in the pedigree </li></ul><ul><li>Trait often skips generations (hidden in heterozygous carriers) </li></ul><ul><li>Trait affects males and females equally </li></ul><ul><li>Possible diseases include: Cystic fibrosis, Sickle cell anemia, Phenylketonuria (PKU), Tay-Sachs disease </li></ul>
  11. 11. Autosomal dominant pedigrees <ul><li>Trait is common in the pedigree </li></ul><ul><li>Trait is found in every generation </li></ul><ul><li>Affected individuals transmit the trait to about 1/2 of their children (regardless of sex) </li></ul>
  12. 12. Autosomal dominant traits <ul><li>There are few autosomal dominant human diseases (why?), but some rare traits have this inheritance pattern </li></ul><ul><li>For example: achondroplasia (a sketelal disorder causing dwarfism) </li></ul>
  13. 13. - Half the people in the Venezuelan village of Barranquitas are affected - A large-scale pedigree analysis was conducted including 10,000 people - Example for one particular family: Huntington’s disease: an example of AD disorder
  14. 14. X-linked recessive pedigrees <ul><li>Trait is rare in pedigree </li></ul><ul><li>Trait skips generations </li></ul><ul><li>Affected fathers DO NOT pass to their sons </li></ul><ul><li>Males are more often affected than females </li></ul><ul><li>Females are carriers (passed from mom to son) </li></ul>
  15. 15. Hemophilia: an example of X-linked recessive disorder
  16. 16. X-linked recessive traits ex. Hemophilia in European royalty
  17. 17. X-linked recessive traits <ul><li>ex. Glucose-6-Phosphate Dehydrogenase deficiency </li></ul><ul><li>hemolytic disorder causes jaundice in infants and (often fatal) sensitivity to fava beans in adults </li></ul><ul><li>the most common enzyme disorder worldwide, especially in those of Mediterranean ancestry </li></ul><ul><li>may give the individual resistance to malaria </li></ul>
  18. 18. X-linked dominant pedigrees <ul><li>Trait is common in pedigree </li></ul><ul><li>Affected fathers pass to ALL of their daughters </li></ul><ul><li>Males and females are equally likely to be affected </li></ul>
  19. 19. X-linked dominant diseases <ul><li>X-linked dominant diseases are extremely unusual </li></ul><ul><li>Often, they are lethal (before birth) in males and only seen in females </li></ul><ul><li>ex. incontinentia pigmenti (skin lesions) </li></ul><ul><li>ex. X-linked rickets (bone lesions) </li></ul>
  20. 20. Pedigree Analysis in real life <ul><li>Remember: </li></ul><ul><ul><li>dominant traits may be rare in a population </li></ul></ul><ul><ul><li>recessive traits may be common in a population </li></ul></ul><ul><ul><li>alleles may come into the pedigree from 2 sources </li></ul></ul><ul><ul><li>mutation happens </li></ul></ul><ul><ul><li>often traits are more complex </li></ul></ul><ul><ul><ul><ul><li>affected by environment & other genes </li></ul></ul></ul></ul>