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NEDWIDEK, MARIATeacher copy
THE MUTATION CONCEPT: taking the bad with the good.Dr. Nedwidek Oct‘13 (GR)
Aim: What are the profits and perils of mutation?
Pre-assessment (night before, in notebook): read Kraus pp 391, 392-399. Identify the basis for heterozygote advantage. State three possible effects of mutation on human survival and give an example of each in nature. Define mechanism. Bring your responses with you to class for discussion. I’ll also return your index cards eliciting the basis for genetic disease.
We start with Discussion of MUTATION EFFECT (allow 10 minutes): First, we consider the significance of mutations regarding human survival based on your lesson preparation detailed above.
Look at this before class if you have time. Here is a 1-minute video to explain the mechanism of one genetic disease we will discuss in class (text of audio below):
DNAi Location:Genome>Tour>genome spots>Sickle cell>About sickle cell:“Sickle cell anemia is a genetic disease that affects hemoglobin, the oxygen transport molecule in the blood. The disease gets its name from to the shape of the red blood cells under certain conditions. Some red blood cells become sickle-shaped and these elongated cells get stuck in small blood vessels so that parts of the body don't get the oxygen they need. Sickle cell anemia is caused by a single code letter change in the DNA. This in turn alters one of the amino acids in the hemoglobin protein. Valine sits in the position where glutamic acid should be. The valine makes the hemoglobin molecules stick together, forming long fibers that distort the shape of the red blood cells, and this brings on an attack.”
PHYSICIANS-IN-TRAINING ACTIVITY (allow <5 mins to diagnose; >10 mins to share):
Today, you, THE FUTURE DOCTORS OF AMERICA will use notes sent and distributed to you as well as an advanced graduate-level clinical genetics text (Thompson and Thompson Genetics in Medicine) to diagnose, state inheritance for, and initiate treatment for 8 patients afflicted with 8 different genetic diseases. You will then convene with your attending physician, Dr. Nedwidek, for “grand rounds” to exchange ideas about your diagnoses and treatment options. Each group will be given a patient history. From this, part of your group will choose from the list of diseases that, according to your resources, fits the profile. You will use the text and the bulletin board to briefly articulate one standard treatment for the disease you diagnose. Only one disease on your list (PKU) is extremely easy to diagnose and treat. Within the remaining 7 diseases, the standard of care for Hemophilia, which is also easy to diagnose, is also relatively simple. We will talk about why this is the case at the end of “grand rounds”. Your groupings were assigned Wednesday, so you are ready to help your patients!
GROUP # ______; NAMES:______
AR=autosomal recessive; AD=autosomal dominant; M.D.=muscular dystrophy, below
XR=X-linked recessive; XD=X-linked dominant;
Thompson’s purple pages are alphabetical by disease
GROUP:DiseaseInheritanceThompson page ref
______Huntington______240-242 & purple
______Holoprosencephaly______338,339 & purple
______Cystic Fibrosis______222-225 & purple
______Phenylketonuria______207-208; Kraus 391
______Tay Sachs______210-212 & purple
______Fragile X______242-243 & purple
______Hemophilia______269, 274 & purple
______Duchenne M.D.______225-229 & purple
Group 1: Ashkenazi Jewish couple brings their six-month old daughter to the doctor with a progressive loss of motor skills and lethargy. Low visual acuity is noted.
Group 2: 2-year old Caucasian girl has poor growth, coughing, and frequent, chronic upper respiratory infections. Tests reveal high sweat chloride levels.
Group 3: 6-year old boy presents with extreme cognitive delay and hyperactivity; learning disabilities and a range of cognitive delay run in the family.
Group 4: 37-year old man had a child die at birth and presents with facial deformity, mild cleft lip, and mild hypotelorism (eyes close together).
Group 5: Three days after birth, blood test on a 3-day-old infant reveals high blood levels of phenylalanine.
Group 6: 30-year old male with slow clot time and high propensity to bruise reveals low levels of clotting factor 9.
Group 7: 6-year-old boy presents with muscle weakness, a Gower’s sign, and developmental delay. His high creatine kinase levels suggest myopathy (muscle disease).
Group 8: 45-year-old man with declining memory and loss of motor control has a family history of similar late onset symptoms.
When I call time, you will read your diagnosis (the name of the disease) and inheritance pattern plus you will read the treatment you suggest. Remember, we must consider why PKU and Hemophilia are so easy to treat at this time in history.
Suggested treatment: