1. Single-gene Disorders

2. Classification of genetic disorders  Single-gene disorders (2%)  Chromosome disorders (<1%)  Multifactorial disorders (60%)

3. Pedigree

4. Pedigree

5. Pedigree

6. Pedigree symbols

7. Types of Mutation class of mutation mechanismfrequencyexamples Genomechromosome missegregation 10 -2 / cell division aneuploidy Chromosomechromosome rearrangement 10 -4 / cell division trans- locations Genebase-pair mutation 10 -10 / cell division point mutations

8. Gene Mutation base-pair mutation Nucleotide Substitutions (point mutations) Deletions Insertions

9. Gene Mutation base-pair mutation Nucleotide Substitutions (point mutations) silent mutations missense mutations (amino acid substitutions) nonsense mutations (premature stop codons) RNA processing mutations Regulatory mutations

10. Gene Mutation base-pair mutation Deletions and Insertions  small number of bases is not a multiple of 3, cause frameshift is a multiple of 3, cause loss or gain of codons  larger gene deletions, inversions, fusions  insertion of L1 or Alu element  dynamic mutations – triplet expansion

11. Genetic disorders with classical Mendelian inheritance DominantRecessive AutosomalAutosomal dominant Autosomal recessive X-linkedX-linked dominant X-linked recessive

12. Autosomal dominant trait

13. Autosomal dominant pedigree

14. Huntington’s disease

18. Autosomal recessive trait

19. Autosomal recessive pedigree

20. Cystic fibrosis

24. X-linked recessive trait

26. X-linked recessive pedigree

27. Hemophilia

28. Hemophilia

29. Hemophilia

30. Literature Biology, eighth edition, Campbell, Reece Unit three: Genetics Chapter 14: Mendel and the Gene Idea Concept 14.4: Many human traits follow Mendelian patterns of inheritance Pages 276 – 279