1. Chapter 2 Genetic Variations

2. Introduction The human genome contains variations in base sequence from one individual to another. Some sequence variants occur within areas that do not encode RNA or protein, and so have no visible effect. Others affect physical characteristics, or phenotype, by altering RNA or protein products. Genetic variants account for some physical differences between individuals, for example hair or eye color, body size, and facial appearance. Some underlie specific medical disorders.

3. DNA Sequence Variants Single base substitutions are the simplest form. – This may occur as a consequence of misincorporation of a base into DNA during replication, or can be a result of changes due to chemical or physical mutagens.

5. Nucleotide Level Changes Base alterations can cause missense mutation, silent mutations and nonsense mutations. Insertions Deletions Duplications Insertions, duplications, and deletions can cause frame shift mutations.

8. DNA Sequence Variants Indels are insertion and deletion events that can occur simultaneously.

13. DNA Repair Systems Three major systems exist for repair of three types of damage. Nucleotide excision repair Base excision repair Mismatch repair

18. Genomic Changes Longer range genomic mutations include deletions, duplications, and inversions involving multiple exons within a gene, and deletions, duplications, or inversions of larger stretches of DNA encompassing multiple genes and chromosomal abnormalities.

19. Genomic Changes Loss of the entire gene leads to reduced levels of expression, referred to as haploinsufficiency. Duplications may lead to increased levels of gene expression. Genomic mutations can be classified into two groups: recurrent mutations in which the size of the deletion or duplication is similar from individual to individual, and changes that are unique to an individual.

24. Genetic Polymorphism Genetic loci variation from individual to individual.

25. Types of Polymorphism Single nucleotide polymorphism. Simple sequence repeats are stretches of DNA in which di, tri, or tetra nucleotide sequences are repeated. Short tandem repeats. These are repeats of tens to hundreds of bases. Copy number variations consist of different numbers of copies of a specific genetic sequence.