Single-gene Disorders

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

Pedigree

Pedigree

Pedigree

Pedigree symbols

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

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

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

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

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

Autosomal dominant trait

Autosomal dominant pedigree

Huntington’s disease

Autosomal recessive trait

Autosomal recessive pedigree

Cystic fibrosis

X-linked recessive trait

X-linked recessive pedigree

Hemophilia

Hemophilia

Hemophilia

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