Huntington’s Disease

1. Huntington’s Disease AnjaliSivendra Yanique Bell February 1, 2010 Period 9/10

2. Huntington’s Disease (HD) • Huntington’s Disease: a brain disorder which affects the way someone thinks, talks and moves. • It destroys the cells in the basal ganglia part of the brain which controls movement, emotion, and cognitive skills. • Overall, people start to experience symptoms when they are 30-50 and as time goes on the disease gets more severe. Carriers of the disease live for 15-20 years after experiencing symptoms. • Symptoms: bad memory, depression/mood swings, bad coordination, uncontrolled movements, difficulty walking, talking or swallowing. * In America, one out of every 30,000 people have Huntington’s Disease.

3. Chromosomal Location • Huntington’s Disease is caused by a mutation in the gene in chromosome 4. • Its main protein, huntingtin, job is to direct delivery of small packages containing important molecules to outside of the cell. • Normally, the DNA coding sequence in one of the genes of Chromosome 4 is “CAG” repeated again and again. How many times it is repeated depends on the particular person, ranging from 10-26. • But for a person with Huntington’s Disease, this DNA coding sequence is repeated an abnormal amount of times, possibly 40 or more. • Therefore, this likely disrupts the function of the genes protein product, but no one is sure how the repition causes the disruption.

4. Mode of Inheritance • One would acquire this genetic disorder by inheriting it in an autosomal dominantpattern • Autosomal Dominant means you only need to get the abnormal gene from one parent in order for you to inherit the disease. One of the parents may often have the disease. • Autosomal- Pertaining to a chromosome that is not a sex chromosome; relating to any one of the chromosomes save the sex chromosomes, 22 pairs, the other two are sex cells X and Y • Dominant- means that if only one parent has the disorder, and it is passed on to the child, they will inherit the disease, even if the other parent gives them a normal chromosome.

5. What are Alleles? • Alleles:copies of genes that pertain to a specific trait. • Everybody has two alleles for each gene. • Alleles come from the parents. During meiosis, the two identical homologous chromosomes containing the set of alleles split. This not only splits the sister chromatids but the alleles as well. This means that the mom gives one allele for the gene and the dad gives the other. • Recessive alleles: two lower case letters EX: rr -a trait that can be covered by a dominant form of the trait • Dominant alleles: two capital letters or one capital letter with a lower case letter EX: RR, Rr - “takes over” and covers up the recessive form of the trait - Usually the normal version of the gene. • Sex-linked traits: Traits that are controlled by genes on the sex chromosomes: X and YEX: XR, Xr, or Y

6. Punnett squares Punnett Squares were invented in 1905 by Reginald Punnett. They are used to predict the phenotypes of the parents’ offspring once you have figured out the genotype. Father’s Genes Father’s Genes H h H H Mother’s Genes Mother’s Genes Directions: Determine the genotypes for each gamete (mom and dad gene). Distribute the alleles to each corresponding row or column. h h Hh hh h h Hh Hh Hh Hh Hh hh Father’s Genes Father’s Genes h h Mother’s Genes H h Mother’s Genes h h H h hh hh HH Hh hh hh hh Hh

7. Probability Father’s Genes • Ratios: 1 : 2 : 1 1 HH : 2 Hh : 1 hh • Percentages 25% : 50% : 25% 25% HH : 50% Hh : 25% hh H h Mother’s Genes H h HH Hh Hh hh

8. Phenotypes and Genotypes • Phenotype: - Ratios- 3 with Huntington’s Disease: 1 normal - Percentages- 75% with Huntington’s Disease: 25% normal • Genotype: - Ratios- 1 HH: 2 Hh: 1 hh - Percentages- 25% HH: 50% Hh: 25% hh H h H h HH Hh Hh hh

9. Phenotypes and genotypes • What does the letters stand for? • Each “H” is the dominant allele, this means that all the offspring with “H” have Huntington’s disease because it is an autosomal dominant disease • Each “h” is the recessive allele, this means the offspring has to have two “h”s to not have the disease • Phenotype- visible characteristics HH- (HD) Hh- (HD) hh- Normal (no HD) • Genotype- the allele combination that makes up the gene HH- Homozygous dominant (HD) Hh- Heterozygous dominant (HD) hh- Homozygous recessive (normal) H h H h HH Hh Hh hh Homozygous: two identical alleles Heterozygous: two different alleles

10. Student practice: punnett squares Father’s Genes Genotype: 2 HH: 2 Hh 50% HH: 50% Hh Phenotype: Ratio: All with disease Percentage: 100% with disease H H M O T H E R’ S G E N E S Ratio: Percentage: H h HH HH Hh Hh

11. 3 Generation hypothetical pedigree = female I. = male II. III. All White- Homozygous Gene/ 2 Healthy Chromosomes Half-Shaded- Heterozygous Gene/ 1 Healthy Chromosome, 1 Mutated Chromosome Full-Shaded- Homozygous Gene/ 2 Mutated Chromosomes

12. Student practice: pedigree • What percent chance do 3rd generation kids have of not having Huntington’s Disease? Why? • If a spouse in the 2nd generation also carried the mutation how would it affect the offspring differently if at all? • If the parent in the 1st generation only had one mutated gene instead of two (Heterozygous), and the spouse only had one healthy gene instead of two (Heterozygous), what would the percentage of inheriting Huntington’s Disease for a child be? I. II. III.