Genetic Mutations

Mutations Mutations: changes in the DNA They may not change the individual in a way that impacts their reproductive success or They can be damaging. We don’t get to choose which one. Mutations can occur mainly in 3 ways: Spontaneously Environmental exposure to mutagens (chemical, radiation, etc.) Inheritance: also called germ line mutations. Hereditary mutations occur in the sex cells (sometimes referred to as “germ cells”) and are therefore passed on from parent to offspring. Most genetic disorders are "multifactorial inheritance disorders," meaning they are caused by a combination of small variations in genes, often in concert with environmental factors. Through research on the human genome, we now know that many common diseases usually caused by genetic alterations in the genes of an individual's cells - such as breast cancer and colon cancer - also have rare hereditary forms. In these cases, gene variants that cause or strongly predispose a person to these cancers run in a family and significantly increase each member's risk of developing the disease.

Genetic Disorders A genetic disorder is a disease caused in whole or in part by a "variation" (a different form) or "mutation" (alteration) of a gene. Single gene disorders: mutation in a single gene. The mutation may be present on one or both chromosomes (one chromosome inherited from each parent). Ex. Sickle cell disease, cystic fibrosis and Tay-Sachs disease are examples of single gene disorders. Chromosome disorders: structural changes within chromosomes, or excess or deficiency of the genes that are located on chromosomes Ex. Down syndrome, for example, is caused by an extra copy of chromosome 21, but no individual gene on the chromosome is abnormal. Multifactorial inheritance disorders : combination of small variations in genes, often in concert with environmental factors. Ex. Heart disease and most cancers are examples of these disorders.

Gene mutations These are mutations within a gene A mutation that only changes one nucleotide is called a point mutation. Substitution Insertion Deletion Resulting proteins can be NOT MADE, NONFUNTIONAL, or BETTER FUNCTIONING

Chromosome Mutation The gene’s location can change on a chromosome This is a structural change

Types of Mutations Wild Type ”Normal”: ACT-GAA-CTG-ATT (Thr-Glu-Leu-Ile) Substitution: ACT-GAC-CTG-ATT (Thr-Asp-Leu-Ile) Deletion: ACT- - - CTG-ATT (Thr-Leu-Ile) Insertion: ACT-GAA-CCT-GAA-CTG-ATT (Thr-Glu-Pro-Gly-Leu-Ile) Frameshift: ACT-GA-C-TGA-TT (Thr-Asp-Stop) Inversion: ACT-GGT-CAA-ATT (Thr-Glu-Gln-Ile)

Causes of Mutation De novo – also called “new” or “spontaneous” mutations, de novo mutations occur in sex cells during or after fertilization. Somatic – also called acquired mutations, these happen to individuals in their lifetime. A mistake may be made when the DNA is being copied to make new cells, or via environmental damage, such as UV radiation. Since only somatic (body) cells are affected, such mutations cannot be inherited.

Nondisjunction Nondisjunction is a chromosome disorder It occurs when either homologous chromosomes fail to separate during anaphase I of meiosis, or sister chromatids fail to separate during anaphase II.

Nondisjunction The frequency of nondisjunction is quite high in humans, but the results are usually so devastating to the growing zygote that miscarriage often occurs very early in the pregnancy. If the individual survives, he or she usually has a set of symptoms - a syndrome - caused by the abnormal dose of each gene product from that chromosome.

Normal Human Karyotype

Down syndrome (trisomy 21) (Extra Chromosome 21) Down syndrome affects 1:700 children Characteristic facial features, short stature, heart defects, susceptibility to respiratory disease, shorter lifespan Often sexually underdeveloped and sterile, usually some degree of mental retardation.

Typical Down Syndrome