“Decoding the genetics of Language” A complex series of face and mouth movements are necessary for speaking fluently.

_________________________________ Due In class: Thursday April 28 th (or before) F Please staple/clip. We will not be responsible for lost pages. ************** PART I “Decoding the genetics of Language” A complex series of face and mouth movements are necessary for speaking fluently. In a threegeneration pedigree of a British family (known as KE Family) half of the family members have difficulties with grammar, comprehension and speech- termed speech language disorder. The underlying disorder is termed “Childhood Apraxia”, a result of the failure to co-ordinate muscle movements of mouth and face that are needed for speech. It is an autosomal dominant disorder with affected individuals being heterozygous for the gene in question. Q1. Based on the information above how many copies of a mutated gene will an individual need to inherit to confer the trait? [1pt] In 2001, geneticists identified the cause of the inherited speech deficit in members of this family and attributed it to a mutation within a single gene FOXP2. (Cecilia S. L. Lai, Simon E. Fisher, Jane A. Hurst, Faraneh Vargha-Khadem and Anthony P. Monaco; Nature 413, 519-523(4 October 2001) This was exciting news as no ‘gene’ had ever been associated with a complex trait such as language. Turns out, FOXP2 is a transcription factor belonging to the winged helix transcription factor family characterized by a highly conserved Forkhead (Fox) domain that binds to distinct DNA sequences in its target gene’s regulatory regions. The mutation within the affected members of the family lies in a single point mutation such that G-A transition changes the amino acid from R553H (R at the 553 position to H) affecting it’s ability to bind to DNA. Q2. FOXP2 is expressed (the protein is found) in many tissues, during development including parts of the brain, the lung, the gut and the heart. Yet, members of the KE family only seem to show deficits confined to regions of the brain implicated in speech development that manifests as speech apraxia. L211 Homework 4 Spring 2016 2 TOt Give one possible explanation for why that may be keeping in mind the nature of the inheritance [2pts] Q3. A lot more research has been done on FOXP2, including the amazing finding that FOXP2 is not unique to humans. In fact, the gene evolved early and is found in a diverse array of animal species- birds, bats and bees. The human FOXP2 differs from our closest relatives the chimpanzees, gorillas and rhesus macaques by just 2 amino acids and from that found in mice by only 3 amino acids! What this tells us is that through evolution a few amino acids (only 2 infact) provided some advantage to the way language evolved and possibly the difference between the ‘uniquely human’ ability of complex language and the rest of the animal kingdom. [1 pts] Based on this information alone which of the following makes sense: A. If a mouse FoxP2 gene is removed, the mouse might “talk.” B. Feeding mice the three amino acids that differ between human and mouse might enable the mice to “talk.” C. Replacing the mutated human FOXP2 gene with a mouse FoxP2 gene is a way to cure speech disorders. D. Putting the human version of FOXP2 gene into a mouse might enable it to form more complex sounds similar to human language L211 Homework 4 Spring 2016 3 TOt Q4. Clearly genetically mutations in FOXP2 lead to problems with speech in the KE family. Researchers are interested in understanding how? Some insight can be gained into this question by learning more about what the normal function of FOXP2 is. Describe an experiment you would do to attempt to answer the question : “ What genes are regulated by FOXP2 in the brain” [4pts] Assume you have all the possible cell lines you need. L211 Homework 4 Spring 2016 4 TOt Part II Developmental Patterning in Drosophila Expression of the Even-skipped (Eve) gene in early Drosophila embryos is under the control of several transcription regulators. In one example, one of the Eve stripes is positioned near the anterior region of the embryo, and its regulatory module contains binding sites for Bicoid and Hunchback (activators) as well as Giant and Krüppel (inhibitors) such that the gene is expressed only in the region where concentrations of the two activators are high and the concentrations of the two inhibitors are low. A reporter gene can be placed under the control of this module, and it can be shown to form a stripe in the same place in the embryo as the corresponding stripe of Eve. Answer the following question(s) based on these findings. Q1. In the following schematic diagrams of an early Drosophila embryo, in which region would you expect to find the reporter protein put under the control of the regulatory module mentioned above? 1pt Circle or write the correct region number: Bicoid 1 Hunchback Giant Krüppel 2 3 4 5 6 7 L211 Homework 4 Spring 2016 5 TOt Q2. What would you expect to happen to the pattern of reporter expression in flies that lack the gene encoding Giant? [2] A. It would be expressed in all seven stripes. B. It would be expressed in stripe 5 only. C. It would expand to cover a broad anterior region of the embryo. D. It would fail to express efficiently in the stripe 2 region. E. It would be expressed throughout the whole embryo. Q3. What would you expect to happen to the pattern of reporter expression in flies that lack the gene encoding Bicoid? [2] A. It would be expressed in all seven stripes. B. It would be expressed in stripe 5 only. C. It would expand to cover a broad anterior region of the embryo. D. It would fail to express efficiently in the stripe 2 region. E. It would be expressed throughout the whole embryo. PART III Revision [1 pt each] 1. Which of the following organisms has a circular chromosome and therefore does not require DNA telomerase to finish chromosome replication? A. Bacteria B. Yeast C. Drosophila D. Mouse 2. The base “uracil” combines with a sugar and three phosphates to form uridine 5’- triphosphate. Which sugar is incorporated into UTP? A. 2’-deoxypentose B. 2’-deoxyribose C. 3’-deoxyribose D. ribose 3. Which of the following elements controls the spatial (where) and temporal (when) expression pattern of an individual gene? A. Enhancer B. Core promoter C. 5` and 3` UTRs D. Intron 4. Which of the following choices is NOT required for DNA synthesis to occur in vitro? A. ADP B. nucleotides L211 Homework 4 Spring 2016 6 TOt C. DNA template D. DNA polymerase 5. Different types of RNA are known to function in the cell. Which of the following choices is an adaptor molecule that links the template (that encodes the protein) to the growing polypeptide chain? A. mRNA B. tRNA C. rRNA D. none of the above are adaptor molecules 6. Upon which of the following choices can DNA polymerase use to start replicating DNA? A. an RNA:DNA primer:template junction B. a DNA:DNA primer:template junction C. single-stranded DNA D. a. or b. 7. What would be the sequence of the partner strand of DNA shown below. (The strand that makes up the other half to make a dsDNA helix) Write your sequence in the 5’-3’ orientation here: ________________________________ P a r t n e r s t r a n d L211 Homework 4 Spring 2016 7 TOt 8. Which of the following characteristics of DNA-dependent DNA synthesis is not the same for DNA-dependent RNA synthesis? A. Synthesis requires a template. B. Initiation involves the recognition of a specific DNA sequence. C. Initiation of synthesis requires a primer. D. Synthesis is catalyzed in the 5′ to 3′ direction. E. All of the choices given are the same for both DNA and RNA synthesis. Fill in the blanks with the appropriate scientific terminology: [0.5 per blank] The instructions specified by the DNA will ultimately specify the sequence of proteins. This process involves DNA, made up of [number] ___________________different nucleotides, which gets ___________________________ into RNA, which is then ________________________into proteins, made up of [number] _______________ different amino acids. In eukaryotic cells, DNA gets made into RNA in the _________________, while proteins are produced from RNA in the _________________. The segment of DNA called a ______________________ is the portion that is copied into RNA; this process is catalyzed by __________________________.