Genetic Mutations

1. BASE PAIRS: ADENINE-THYMINE GUANINE-CYTOSINE Genetic Mutations

2. Types of Mutations GERMLINE MUTATIONS • Germline mutations = Inherited mutations • Most inherited mutations are recessive • Effects of germline mutations • Either no change in phenotype • Very small change in phenotype • Or lethal changes in phenotype • Relatives can not marry as they have similar genes and a have a higher chance of passing genetic mutations to their offspring SOMATIC MUTATIONS • Silent mutations (No effect whatsoever) • Frequently caused by environmental factors such as exposure to chemicals or ultraviolet radiation • Alterations in DNA after conception • Somatic mutations are not inherited nor passed down to offspring

3. How Mutations are Caused • Missense mutation This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene. • Nonsense mutation A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all. • Insertion An insertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result, the protein made by the gene may not function properly. • Deletion A deletion changes the number of DNA bases by removing a piece of DNA. Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the resulting protein(s). • Duplication A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of mutation may alter the function of the resulting protein. • Frameshift mutation This type of mutation occurs when the addition or loss of DNA bases changes a gene’s reading frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can all be frameshift mutations. • Repeat expansion Nucleotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of 3-base-pair sequences, and a tetranucleotide repeat is made up of 4-base-pair sequences. A repeat expansion is a mutation that increases the number of times that the short DNA sequence is repeated. This type of mutation can cause the resulting protein to function improperly.

4. Down Syndrome Every year 800 to 1000 children in the U.S are born with down syndrome. The most common form of Down syndrome is often called "trisomy 21," because individuals with this condition have three copies of the 21st chromosome. This results in cells being unable to control the amount of proteins being developed. Nondisjunction: This is when a pair of chromosomes fail to separate during egg or sperm formation. This causes there to be an extra 21st chromosome in the embryo. Then this extra chromosome copies itself into all further cells developed. Nondisjunction events seem to occur more frequently in older women. This may explain why the risk of having a baby with Down syndrome is greater among mothers age 35 and older. There is no definitive scientific research that indicates that Down syndrome is caused by environmental factors or the parents' activities before or during pregnancy.

5. Down Syndrome contd. Facial features: - A flat face - A small, broad nose - Abnormally shaped ears -A large tongue -Slightly slanted eyes They also exhibit moderate to severe mental retardation. Children with Down syndrome usually develop more slowly than their peers, and have trouble learning to walk, talk, and take care of themselves. Because of these medical problems most people with Down syndrome live to be about 50 years of age. No one knows exactly why this chromosomal error occurs, but it does appear to be related to the age of the mother. At age 25, a woman has a one in 1,250 risk for having a child with Down syndrome. The risk increases to one in 952 at age 30, to one in 378 at age 35, to one in 106 at age 40 and one in 35 at age 45. However, 80% of children born with Down syndrome are born to mothers under the age of 35. This is because most babies, in general, are born to younger women. People with Down syndrome have an increased risk of developing a number of medically significant problems: - Respiratory infections - Leukemia - Heart defects