Lab 5: Human Genetic Disorders

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1 Lab 5: Human Genetic Disorders Adapted from Learn.Genetics and Bio10 Laboratory Activities by V. Annen A genetic disorder is a disease that is caused by an abnormality in an individual's DNA. Abnormalities can range from a small mutation in a single gene to the addition or subtraction of an entire chromosome or set of chromosomes. Three common categories of genetic disorders are: Single gene disorders These disorders are caused by a mutation in the DNA sequence of one gene. Genes code for proteins and when a gene is mutated its protein product can no longer carry out its normal function. Single-gene disorders are inherited in autosomal dominant, autosomal recessive, and X-linked patterns. Chromosome abnormalities In these disorders, entire chromosomes, or large segments of them, are missing, duplicated, or otherwise altered. Gametes with extra or missing chromosomes can be formed during meiosis and result in individuals with an abnormal number of chromosomes. An example is Down syndrome (trisomy 21). Multifactorial disorders These disorders are caused by mutations in multiple genes. Environmental factors also play a role in many multifactorial disorders. Many common chronic disorders, including hypothyroidism, colon cancer, breast/ovarian cancer, Alzheimer s disease are multifactorial. Heritable traits such as height, eye color and skin color are also multifactorial. Examples of single gene disorders: 1. Phenylketonuria (PKU) is caused by a mutation in the PAH gene located on Chromosome 12. The gene codes for a protein called phenylalanine hydroxylase (PAH). This enzyme breaks down the amino acid phenylalanine. When this gene is mutated, the shape of the PAH enzyme changes and it is unable to properly break down phenylalanine. Excess phenylalanine in the blood is toxic to nervous tissue and can cause brain damage. PKU is an autosomal recessive disorder. Answer the questions about this genetic disorder on the Group Lab Report sheet. 2. Achondroplasia Dwarfism is caused by a mutation in the FGFR3 gene located on Chromosome 4. Mutations in this gene result in abnormal skeletal formation. 80% of people with Achondroplasia have average-size parents; these cases result from a new mutation in the FGFR3 gene. In the remaining cases, Achondroplasia is inherited in an autosomal dominant pattern. The homozygous dominant genotype is lethal and individuals are often stillborn or die shortly after birth. Answer the questions about this genetic disorder on the Group Lab Report sheet.

2 3. PTC: Genes and bitter taste. PTC stands for phenylthiocarbamide, a chemical compound made up of carbon, hydrogen, nitrogen, and sulfur. The ability to taste PTC is determined by a single gene, TAS2R38, is located on Chromosome 7. The gene codes for a taste receptor on the tongue that binds PTH. There are two common forms (or alleles) of the RTC gene. One is a tasting allele, and the other is a non-tasting allele. About 75% of the population has the ability to taste PTC and the other 25% can't taste PTC. Taste PTC paper and record your genotype and phenotype on the Group Lab Report sheet.. Examples of chromosome abnormalities Chromosomal abnormalities can be screened for during a woman s pregnancy by taking a sample of cells from the placenta, amniotic fluid, or umbilical cord to examine the baby's chromosomes and determine if he or she has the correct number and the correct size of chromosomes. 1. Trisomy 18 is a genetic disorder in which a person has a third copy of chromosome 18. It is a relatively common syndrome that is three times more common in girls than boys. The extra chromosome interferes with normal development. 2. Down syndrome (Trisomy 21) is caused by an extra copy of chromosome 21. People with Down syndrome have distinct facial features and moderate to severe mental retardation. They also have an increased risk of developing a number of medical problems. Because of this, most people with Down syndrome have a decreased life expectancy. About half live to be 50 years of age. 3. Klinefelter Syndrome is a disorder that affects only males. Males normally have an X chromosome and a Y chromosome (XY). But males who have Klinefelter syndrome have an extra X chromosome (XXY), giving them a total of 47 instead of the normal 46 chromosomes. Klinefelter syndrome is one of the most common genetic abnormalities. It affects between 1 in 500 and 1 in 1,000 males. 4. Turner Syndrome is caused by a missing X chromosome. Females with Turner syndrome have the XO genotype (only 1 X chromosome). The OY genotype is lethal so there are no males with Turner Syndrome. Complete the karyotypes in the Group Lab Report and determine what genetic disorders, if any, are indicated. Multifactorial disorders Example: heart disease. Construct a pedigree using the instructions provided. Turn in your pedigree with your lab report.

3 Names Lab 5 Group Results Sheet Single Gene Disorders 1. Determine the probability of two carriers for PKU having a child with PKU. 2. Examine the results of the Silva Family s genetic testing. The dominant (normal) gene is larger (4.2 kb) and does not travel as far in a gel during electrophoresis. Does their baby (C2) have PKU? P1 P2 C1 C2 P1 and P2 are the parents: C1 is the first child, C2 is the second. 3. Does the first child (C1) have the disorder or is s/he a carrier? 4. What type of diet is prescribed to individuals with PKU? 5. Give the genotype of an adult with achondroplasia dwarfism. 6. What are the chances that two achodroplasic dwarfs will have a normal sized child?

4 7. Give the genotypes for individuals with the following phenotypes: [T = tasting gene, t = non-tasting gene] a. taster finds PTC intensely bitter b. taster finds PTC somewhat bitter c. non-taster 8. Taste PTC paper and record your genotype and phenotype. 9. What might be the evolutionary advantage of being an individual capable of detecting bitter tasting substances? Karyotypes: Screening for Chromosome abnormalities A karyotype is an organized profile of a person's chromosomes. In a karyotype, chromosomes are arranged and numbered by size, from largest to smallest. 10. Complete the Cut n Paste Karyotyping activity and show your work to the instructor or hand it in with your lab report. 11. Can you determine if the child is male or female from the karyotype? How? 12. Explain what trisomy is and how it occurs.

5 13. Examine the 4 karyotypes on the sheet provided in lab. Fill in the following information about each karyotyype: Karyotype #1 Karyotype #3 Karyotype #2 Karyotype #4 Multifactorial disorders Construct a pedigree using the instructions provided. Turn in your pedigree with your lab report.