1. As this disease is most commonly prevalent in the elderly, some members of the class may have relatives with this disease so please be a respectful and a mature audience.

2. Alzheimer’s Disease Lizzy Butler & Efe Osemeha Period 3

3. Background Information  Alzheimer’s Disease is a neurological disease that kills neurons causing the loss of memory.  Consists of 3 stages/levels: mild, moderate, severe  Symptoms include: confusion, short attention spans, and mood swings.  Includes two abnormal structures - plaques and tangles  Most common, Late-onset form affects people over 60.

4. Most common form associated with apoE gene on chromosome 19 Most common form associated with apoE gene on chromosome 19 Gene has 3 forms: 1 increases risk of AD, other 2 helps protect against AD Gene has 3 forms: 1 increases risk of AD, other 2 helps protect against AD Mutations in genes found on chromosomes 1, 14, 21 cause rare form of early-onset Mutations in genes found on chromosomes 1, 14, 21 cause rare form of early-onset

5. Mode of Inheritance  Early onset is inherited from an Autosomal Dominant Pattern  Autosomal means that it is not linked to the X or Y chromosomes.  Dominant means that if one copy of the allele is present, the person will have the disease.  Inheritance of Late onset is uncertain  Environmental factors such as chosen lifestyles may play a factor.

6.  Specific sequence of nucleotides on DNA that determine gene coding  Can be variations in this sequence; each variation is called an Allele  Inherit one allele from each parent for each gene  Dominant allele (R) determines outcome regardless of the second allele, while recessive allele (r) requires a match. Gene is represented as combination (RR, Rr, rr)  If sex-linked, represented as X r, X R, or Y

7. Punnett Square IIn Punnett Squares: probability for child to have genetic offspring determined by parent's genes. (Represents Probability per child) FFemale represented on left side; male represented on top Homozygous recessive Heterozygous dominant Homozygous dominant

8. Probability Using Punnett Square Ratios Ratios (Must add up to 4 since there are 4 possible combinations) (Must add up to 4 since there are 4 possible combinations) homozygous dominant : heterozygous dominant : homozygous recessive 1 : 2 : 1 1 AA 2 Aa 1aa Percentages: (Must equal to 100%) homozygous dominant: heterozygous dominant: homozygous recessive 25% 50% 25% 25% AA 50% Aa 25%aa

9. Meaning of Letters So what does Aa, aa, and AA mean? So what does Aa, aa, and AA mean? If A represents the dominant allele Alzheimer’s and a represents If A represents the dominant allele Alzheimer’s and a represents the recessive allele non- Alzheimer’s, then we can assume that: the recessive allele non- Alzheimer’s, then we can assume that: Phenotype: (what is seen) Phenotype: (what is seen)  AA: Alzheimer's gene  Aa: Alzheimer’s gene (Non-Alzheimer’s gene carrier)  aa: Non-Alzheimer’s gene Genotype: (what is in the genes) Genotype: (what is in the genes)  AA: Homozygous Dominant (Alzheimer’s)  Aa: Heterozygous Recessive (Alzheimer's)  Aa: Homozygous Recessive (Non-Alzheimer’s)

10. Phenotype: Ratios: 3 Alzheimer's: 1 Non- Alzheimer’s Percentages: 75% Alzheimer’s: 25% Non- Alzheimer’s Genotype: oRoRoRoRatios: 1AA: 2Aa: 1aa oPoPoPoPercentages: 25% AA : 50% Aa : 25% aa

11. Student Practice with Punnett Square If an heterozygous Alzheimer’s father marries a homozygous non- Alzheimer’s mother, use a Punnett square to illustrate the probability of a child developing Alzheimer’s. Genotype: –R–Ratio: 2 AD, 2 non-AD –P–Percentage: 50% AD - 50% non AD Phenotype: –R–Ratio: 2 Aa : 2 aa –P–Percentage: 50% Aa : 50% aa A a a a Aa Mother’s Genes Father’s Genes Aaaa

12. 3 Generation Hypothetical Pedigree Circle- female Square- male –All white- homozygous recessive gene (has 2 copies of “healthy” gene) –All green- homozygous dominant (has AD, 2 copies of “bad” gene) –Half green/half white- heterozygous (person has AD, one healthy, one bad) I II III

13. Student Practice How do we know that neither of Generation I are homozygous dominant? Is it possible for the middle daughter of Generation II to have an offspring that does not suffer from Alzheimer’s? Is there any chance that offspring of the first daughter in Generation II develops Alzheimer’s? I II III Key:Key: –Circle: female –Square: male –Shaded in: Alzheimer’s –Not shaded in: non- Alzheimer’s –Half shaded in: Dominant, Alzheimer’s