Pedigree Analysis

1. Pedigree Analysis Lecture 8 Dr. AttyaBhatti

2. Pedigree • A pictorial representation of a family history, essentially a family tree that outlines the inheritance of one or more characteristics.

3. Introduction: • A “family tree,” drawn with standard genetic symbols, showing inheritance patterns for specific phenotypic characters is called pedigree. • Analysis of inheritance pattern of phenotypic characters in a pedigree is called pedigree analysis. • Propositus/Proband: A member of a family who first comes to the attention of a geneticist. • The investigator then traces the history of the phenotype in the propositus back through the history of the family and draws a family tree, or pedigree.

4. Goals of Pedigree Analysis • 1. Determine the mode of inheritance: dominant, recessive, partial dominance, sex-linked, autosomal, mitochondrial, maternal effect. • 2. Determine the probability of an affected offspring for a given cross.

5. Pedigree Analysis • Males in a pedigree are represented by squares, females by circles. A horizontal line drawn between two symbols representing a man and a woman indicates a mating; children are connected to their parents by vertical lines extending below the parents. • Persons who exhibit the trait of interest are represented by filled circles and squares. • Unaffected persons are represented by open circles and squares. • Each generation in a pedigree is identified by a Roman numeral; within each generation, family members are assigned Arabic numerals, and children in each family are listed in birth order from left to right. • Deceased family members are indicated by a slash through the circle or square.

6. Basic Symbols

7. Generations labelled roman numerals I, II, ... Individuals labelled arabic numerals 1, 2, ...

8. Inheritance Pattern • Autosomal Dominant Inheritance • Autosomal Recessive Inheritance • X-Linked Inheritance • X-Linked Recessive Inheritance • X-Linked Dominant Inheritance • Y-linked Inheritance

9. Autosomal recessive disorders 1. Appears in both sexes with equal frequency. 2. Trait tends to skip generations. 3. Affected offspring are usually born to unaffected parents. 4. When both parents are heterozygous, approximately 1/4 of the offspring will be affected. 5. Appears more frequently among the children of consanguine Marriages. • The affected phenotype of an autosomal recessive disorder is determined by a recessive allele, and the corresponding unaffected phenotype is determined by a dominant allele. For example, the human disease phenylketonuria is inherited in a simple Mendelian manner as a recessive phenotype.

10. Autosomal recessive disorders Pedigree of a rare recessive phenotype determined by a recessive allele.

11. Autosomal Dominant disorders 1. Appears in both sexes with equal frequency. 2. Both sexes transmit the trait to their offspring. 3. Does not skip generations. 4. Affected offspring must have an affected parent, unless they possess a new mutation. 5. When one parent is affected (heterozygous) and the other parent is unaffected, approximately 1/2 of the offspring will be affected. 6. Unaffected parents do not transmit the trait.

13. Autosomal dominant disorders • Key points are, • The main clues for identifying a dominant disorder with Mendelian inheritance are that the phenotype tends to appear in every generation of the pedigree and • That affected fathers and mothers transmit the phenotype to both sons and daughters.

14. Autosomal dominant disorders Fig: Pedigree of a dominant phenotype determined by a dominant allele.

15. X-Linked Recessive Inheritance 1. More males than females are affected. 2. Affected sons are usually born to unaffected mothers; thus, the trait skips generations. 3. A carrier (heterozygous) mother produces approximately 1/2 affected sons. 4. Is never passed from father to son. • All daughters of affected fathers are carriers. E.g; Hemophilia

16. X-Linked Recessive Inheritance

17. X-linked recessive disorders Fig: Pedigree showing that X-linked recessive alleles expressed in males are then carried unexpressed by their daughters in the next generation, to be expressed again in their sons. Note that III-3 and III-4 cannot be distinguished phenotypically.

18. X-Linked Dominant Inheritance 1. Both males and females are affected; often more females than males are affected. 2. Does not skip generations. Affected sons must have an affected mother; affected daughters must have either an affected mother or an affected father. 3. Affected fathers will pass the trait on to all their daughters. 4. Affected mothers (if heterozygous) will pass the trait on to 1/2 of their sons and 1/2 of their daughters.

19. X-Linked Dominant Inheritance

20. X-linked dominant disorders. Fig: Pedigree showing that all the daughters of a male expressing an X-linked dominant phenotype will show the phenotype.

21. X-linked dominant disorders. Pedigree showing that females affected by an X-linked dominant condition are usually heterozygous and pass the condition to half their sons and daughters

22. Y-linked inheritance • Only males are affected. • Is passed from father to all sons. • Does not skip generations.