Q NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE In Sickness and in Health: A Trip to the Genetic Counselor by Barry Chess Natural Sciences Division Pasadena City College, Pasadena, CA Updated by Tina Jones Shelton State Community College, Tuscaloosa, AL Part I—Pedigree Construction Greg and Olga were both a little worried. Starting a family presented choices and responsibilities far more long-reaching and complex than anything either of them had encountered before, and sitting here in the reception area of the genetic counselor’s office they were beginning to feel the pressure. Th ey had met four years earlier in the hemophilia clinic where Greg was waiting for his brother Jeff to get an injection of factor viii, a protein that helps the blood to clot. When a person’s factor VIII level is very low (less than 1% of normal), even the smallest cuts can be troublesome and uncontrolled internal bleeding is common. Complications include swelling, joint damage, and an increased likelihood of neurological complications due to intracerebral bleeding. Even simple surgical procedures such as tooth extractions become far more risky. Jeff’s condition was noted by his pediatrician shortly after birth when his circumcision bled profusely. Since then, Jeff has received monthly injections of factor viii, either at home or (twice a year) at a clinic where his physical condition is reviewed by a physician’s assistant. At fi rst these injections contained clotting factor isolated from the blood of human donors but, for the last 10 years or so, he has received recombinant clotting factor, which is genetically engineered. It was in that clinic waiting room that Greg struck up a conversation with Olga, who was waiting for her uncle to finish his exam and receive an injection of clotting factor. Like Jeff, Olga’s uncle also suffered from hemophilia A due to factor viii deficiency. Beginning with this common experience, Greg and Olga quickly fell in love and were married the following year. They are now thinking about starting a family of their own, but are concerned about the risks of passing on genetic diseases to their children. Th ey know for example that hemophilia A is an inherited disease, and several of Greg’s relatives suffer from myotonic dystrophy, a muscle weakening disease that also runs in families. As a fi rst step, the genetic counselor has asked them to fi ll out a narrative history listing their relatives, relationships, and if they were affected by any genetic diseases that they know of. Th e forms are seen below. ????: Greg I have one brother and one sister, neither of whom are married. My brother suffers from factor VIII deficiency, but no one else in my family does. My mother has two brothers and one sister. One of my uncles and one of my aunts are affected by myotonic dystrophy. My affected aunt married an unaffected man and they have a young, seemingly unaffected daughter. My other uncle is unaffected, as is my mother. Our primary care doctor has said that because both my mother and uncle are over fifty years old and show no symptoms, they do not have the disease. My father is completely normal. He was adopted from an orphanage and nothing is known about his family. My maternal grandmother was an only child who also suffered from myotonic dystrophy. Her husband (my grandfather) was one of seven children (four boys and three girls). No one in the family seems to know much about the health status of my grandfather or his brothers. Both of my parents are alive but all of my grandparents are deceased. “In Sickness and in Health” by Barry Chess Page 1 NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE ????: Olga I have two brothers, one of whom has factor VIII deficiency. The brother with the disease is married to a woman who does not have the disease. They have two young boys, both normal. My father is an only child who does not suffer from anything and his parents also are only children who do not suffer from any diseases. They are all still living. My maternal grandmother is healthy and had a sister who died just after birth. She married my grandfather who was one of four children, all boys, none of whom were affected by any disease that anyone is aware of. My grandparents had two children, my mother and my uncle. My uncle has hemophilia but my mom doesn’t. My uncle married my aunt (who is unaffected) and they had two children, neither of whom showed any sign of any disease. Their boy is still single but their girl got married, to a normal man, and had a son, who has hemophilia A. “Good afternoon” said the woman rising to greet them, “I’m Dr. Ciletti. It’s good to fi nally_meet _ you in person “Nice to fi .” nally_ put _a _face_ to _the _voice.__ I'm Greg, and this is my wife Olga.” “Nice to meet you,” Olga said, taking a seat across the desk from Dr. Ciletti. " This whole having kids thing is more nerve-wracking when you really start to think about it.” “You’re doing exactly the right thing. Th ere is no sense in worrying about things unless you have to. Maybe I can set your mind at ease a little bit. To begin with, I know that you’re both concerned about factor VIII deficiency _and myotonic dystrophy because of the family history. Is there anything else that you’d like to know?” “Well,” began Olga, “the fact that we both have these diseases in our family and there is a chance that we could pass them on to our children has opened our eyes a little bit, but we’d also like to know if you can predict other diseases that don’t run in our family. Like my best friend in high school had cystic fi brosis and she died when she was only twenty four, and was sick almost all the time.” “Okay, well, cystic fi brosis doesn’t look like it is in either of your family histories so it’s probably not worth worrying about. But, we can spend a little time going over the chance that you both carry a gene that has never before shown its face. Th e first _step _is _we have to convert the family information you two have provided into a graphical representation called a pedigree. From there we can begin to correlate family relationships with the appearance ofspecific diseases.” Question 1. What would a pedigree of Greg and Olga’s families look like? Concentrate simply on family relationships and affected persons. Make a sketch of the pedigree, sign and date it, and insert a photo of your drawing below. Be sure that all labels are clear. Part II—Autosomal Dominant Traits “Great, so this looks like an accurate representation of your family, right?” Dr. Ciletti asked. “Looks good to me,” replied Greg. “My family is so small, there’s not much to miss until you get to my grandparents,” said Olga. “Well, factor viii deficiency and myotonic dystrophy are inherited in completely different ways. Come to think of it, you asked about cf as well and …” “cf?” asked Greg. “Cystic fi brosis,” Dr. Ciletti continued. “I was about to say that cystic fi brosis is inherited in a manner diff erent than both of the other diseases you are concerned about, but let’s tackle them one at a time.” “Myotonic dystrophy is an autosomal dominant disease and it is the easiest to pick out of a pedigree. Now Greg, even though you have an uncle and aunt as well as a grandmother who all have the disease, you don’t and there is no way that you will pass this disease on to your children. So that is the fi rst piece of good news.” “But don’t a lot of genetic diseases skip a generation?” Greg asked. “And even if it doesn’t, my mom has two siblings with the disease. Could she be a carrier and just pass the disease on to me? For that matter, could I be a carrier?” “Yes, could he be a carrier?” Olga added. “Absolutely not,” Dr. Ciletti said. “Let me show you why.” Questions 1. Do autosomal dominant disorders skip generations? 2. Could Greg or his mother be carriers of the gene that causes myotonic dystrophy? Why or whynot?........................