#1 MAKE OBSERVATIONS
Some genetic diseases are very common in people with certain heritages. Examples include sickle cell anemia in persons from African descent, Tays Sachs in Jews from Germany or Eastern Europe, and cystic fibrosis in Caucasians.
#2 ASK QUESTIONS
Is there a way to narrow down genetic issues specific to certain heritages?
#3 HYPOTHESIS
There are factors within a person’s genetic code (DNA) and factors within the way persons of a certain heritage live that concentrate genetic issues within a particular heritage.
#4 PREDICTION
Genetic issues will be the result of changes within the affected individual’s DNA that mean they have differences in the way their cells work that results in the disease. These negative changes will be found more commonly in certain heritages because of behavior like how much the population mixes with other populations or if having a mild form of the disease gives a survival advantage.
#5 TEST WITH CONTROLS
The next part of the test would include surveys, finding out how the persons live. Some questions would include how did you find your husband or wife? Where do you live? Do people move away often? Do new people come into your community from elsewhere often? What is your usual diet? What diseases do people you know die from? Are the answers to this question the same or different from ten years ago or for their parents or their grandparents (if they know)? Basically, any questions that might hold clues to why this change within the DNA might be useful to the people living the way these people do.
Controls could be data from people with heritages where the disease is uncommon.
#6 EXPLORATION
Clancy, S., 2008, Genetic mutation. Nature Education.
http://www.nature.com/scitable/topicpage/genetic-mutation-441
- Changes in the genetic code of only one piece (base) of the DNA can change the way the cell works
- Sickle cell is a disease where just one change makes the red blood cells look different and not work correctly
- Not all changes (mutations) result in a change in function, those are called silent mutations
- Some changes can be helpful, like the mild form of sickle cell (when the changed DNA comes from just one parent) as it means you can survive malaria more often
- Having one copy of a changed gene is called being a “carrier”
Sickle cell is a very bad disease when you have two copies of the changed DNA but having only one copy is helpful because it helps a person survive malaria. That makes that change more common for people born in Africa as malaria is a common disease there so people with one copy may live longer and have more children.
This is an example of a disease where a change in the DNA causes a genetic issue but something about the way people live (living in Africa, where there is malaria) has concentrated the genetic issue for people having that heritage.
Needing changes in DNA from both parents makes it harder to follow where the change is in the population. Since there is no outward clue that someone has the change (other than surviving malaria) the change in the gene can be there without having a bad effect.
“Tay-Sachs disease,” 2012, Genetics Home Reference. http://ghr.nlm.nih.gov/condition/tay-sachs-disease
- Tay-Sachs disease can be caused by changes in a gene called HEXA, which changes how fats are broken down in cells causing the disease
- Mutations that stop HEXA from doing its function cause the disease
- Like sickle cell, a person needs changed HEXA genes from both parents to have the disease
- Children who have Tay-Sachs usually die very young
- Carriers of Tay-Sachs don’t have any symptoms (is this the same or different than the sickle cell explanation?)
- Besides Jewish people of eastern and central Europe, the mutation is more common in Old Order Amish and Cajun
This tells the gene change that causes the genetic issue of Tay-Sachs disease but it does not help explain why it is more common in Jewish people. Is there something the same between Jewish people, Old Order Amish, and Canjun that could explain the increase in the mutation in all of those heritages?
Freedman, J. , 2009, Tay-Sachs disease. pp. 33-34.
http://books.google.com/books?id=iSYEEHOHXYkC&pg=PA31&dq=tay+sachs+disease+founder+effect&hl=en&sa=X&ei=44L6UeW9J5TI4AP47ICwBw&ved=0CEoQ6AEwAw#v=onepage&q=tay%20sachs%20disease%20founder%20effect&f=false
- There are several characteristics that are common in heritages that show an increased occurrence of Tay-Sachs disease
- One is that they descend from a small, isolated group of people called a “founder” population
- A second is that they tend to stay isolated and marry only within their heritage
- Jewish, French-Canadian, Cajuns, and Irish Americans all show increased occurrence of a mutation that causes Tay-Sachs – they all started from small founder populations and, until recently, tended to marry within their own heritage
- Because so many heritages that started from founder populations and stay isolated show increased Tay-Sachs the theory is that these conditions are responsible for the situation, called a “founder effect”
- There are actually many mutations, that cause Tay-Sachs, but they all cause the HEXA gene to not work correctly
Although this is different than the sickle cell situation, because so many heritages have increased Tay-Sachs disease this explanation makes sense. It would be hard to find other common things between all these different heritages like a disease or other problem that being a carrier would provide an advantage. So this founder effect is a good possibility for this kind of genetic issue.
“Cystic fibrosis,” 2012, Genetics Home Reference.
http://ghr.nlm.nih.gov/condition/cystic-fibrosis
- Cystic fibrosis is caused by a mutation in a gene called CFTR, which changes how mucus is produced in cells causing the disease
- Like sickle cell and Tay-Sachs, to have cystic fibrosis you have to have changed CFTR genes from both parents
- People who have cystic fibrosis used to die young, but now live into adulthood
- Carriers of cystic fibrosis don’t have any symptoms (is this the same or different than the sickle cell explanation or the Tay-Sachs situation?)
- Cystic fibrosis is much more common for the white population (Caucasian heritage) than for African-Americans or for Asian Americans
- Like Tay-Sachs, there are many different mutations that cause the CFTR gene to no longer work and cause the cystic fibrosis disease
- These different mutations in the CFTR gene are responsible for different severities of the disease
- Mutations in other genes might cause the disease to be more or less severe for particular people
This reference gives basic information about cystic fibrosis and the mutations that causes it. It also gives information about the frequency of the disease within different heritages. But there is no information about why this mutation would be more common in the white population than others. Could it be the founder effect, like for Tay-Sachs, or some advantage for carriers focused on the white population, like sickle cell for African heritage or is there another explanation?
MacKenzie, D., 7 September, 2006, Cystic fibrosis gene protects against tuberculosis. NewScientist.
http://www.newscientist.com/article/dn10013-cystic-fibrosis-gene-protects-against-tuberculosis.html#.UfqSYGTzYqQ
- Scientists think that the CFTR mutation could provide an advantage to carriers
- Poolman and Galvani reviewed a number of different diseases to try to find one that the CFTR mutation could provide an advantage and also had a large impact on the white population, as compared to other heritages
- Although being a CFTR carrier could help in survival of cholera or typhoid, the effect on the white heritage was not focused enough to explain the cystic fibrosis mutation continuing to be present in that heritage and not others
- Tuberculosis (TB) did have both the focus on the white population and could be where an advantage for carriers is found
- There was a large epidemic between 1600 and 1900 of TB that could explain the presence of the CF gene mutation in the white population
- They supported this using computer models
- Computer calculations predict that CF rates should go down by 0.1% each year if the advantage from TB survival goes away
- But now TB is increasing, rather than decreasing because antibiotics are not working against the disease anymore
The cystic fibrosis situation looks like it is similar to sickle cell anemia but with tuberculosis rather than malaria providing the advantage to a person who is a carrier to the mutation. The founder effect seems less likely, particularly because the white population didn’t start from a small founder group and they haven’t mainly married within a small group of people. It is interesting that the occurrence of the CFTR mutation should go down over time, but there are still problems with this – how slowly it happens and the possible increase of TB as a global health problem because antibiotics don’t work on the disease anymore.
Gilham, N., 2011, Genes, Chromosomes, and Disease. pp. 70-71.
http://books.google.com/books?id=cpAqMmAKkkUC&pg=PA71&lpg=PA71&dq=cystic+fibrosis+founder+effect&source=bl&ots=thfWG_md7h&sig=oo3T0MeGLXlduyaiVlZwZ9Y06xw&hl=en&sa=X&ei=iJj6UYGjA9Ol4AO6goGwBQ&ved=0CFIQ6AEwBzgK#v=onepage&q=cystic%20fibrosis%20founder%20effect&f=false
- Not all scientists agree with the work by Poolman and Galvani on TB selective advantage for CFTR carriers
- Other scientists believe that diarrhea, cholera, and typhoid resistance may be responsible
- A mouse model was used to show the possibility of resistance to cholera by the CFTR mutation, but these experiments did not hold up to further testing in other mouse models and humans
- A mouse model was also used to try to prove carrier resistance to typhoid based on the idea that CFTR is what the bacteria binds to when it enters the cell
- Gilham criticizes the Poolman and Galvani study (discussed by MacKenzie) that the basis for the resistance is weak even though the computer models support resistance to TB keeping the mutation in the white population
- Gilham states he believes the typhoid data to be strongest
- But there is a problem in that typhoid is common in tropical areas where non-whites originally lived but the incidence in the non-white population is low
This book, published in 2011, shows that there is still a lot of controversy as to why the CTFR gene is higher in those of white heritage compared with other heritages. This shows how difficult it is to look to the past and predict what could have caused an advantage to a particular group of people. Depending on what part of the proof scientists put the most emphasis – experimental showing of a carrier advantage or a computer program that fits the occurrence of the gene mutation in the present population, different explanations can be found.
One way to solve this question is to keep doing experiments into the possible reasons that the CTFR gene might cause carriers to be resistant to TB. If there is a better explanation than the current one, this might become more convincing. Also, better data concerning the historical occurrence of typhoid in the various heritages that have low cystic fibrosis should be gathered to make sure this is a real reason to dismiss the typhoid data. Unfortunately, the global rise of TB is going to make looking at this even more difficult in the future.
In the end, knowing the actual reason the mutation occurs more in the white heritage population doesn’t help people with cystic fibrosis but it can help focus screening for the CTFR gene mutation to people having heritages most likely to have the mutation.
#7 REFINED, IMPROVED, MORE DETAILED QUESTON
How can you distinguish between the genetic (DNA-based) and behavior or environmental (evolutionary-based) contributions to determine what is the most likely reason a genetic issue is more common within certain heritages?
