Part II. Genetics of Sickle Cell Anemia:
Sickle cell anemia is a classic Mendelian trait. That means that getting the disease is determined by the presence or absence of one particular gene, in this case, the gene for the beta chain of hemoglobin. So let’s review basic genetics.
You can represent the single gene that codes for the beta chain of hemoglobin by using the letter H or S for the normal hemoglobin allele, h or s for sickle cell hemoglobin allele. This capital/small letter symbolism conveys that sickle cell anemia (h or s) is an autosomal dominant or recessive disease? __________________
Allele is a genetic term that refers to different versions of the same gene, in this case the normal hemoglobin allele (H) or the sickle cell hemoglobin allele (h). Autosomal refers to a gene on any chromosome other than a sex-determining chromosome (X and Y).
Recall also that individuals have two copies of each gene, and if the individual is homozygous, the two gene copies are identical alleles, and if the individual is heterozygous, the two gene copies are different alleles.
Check your understanding:
An adult with homozygous normal hemoglobin would have the genotype: ______
An adult with sickle cell hemoglobin would have the genotype: _______
An adult with normal hemoglobin, but heterozygous for the sickle cell trait, would have the genotype: __________. A heterozygote is sometimes referred to as a carrier because the person has no signs of the disease, he/she can pass on the disease gene to his/her offspring.F
(Most texts refer to sickle cell disease as autosomal recessive. Some texts refer to the sickle cell gene as co-dominant, because both the normal and sickle genes make protein, but when a person has one copy of each gene, he/she does not manifest the full-blown disease.)
Gamete Formation:
Recall the process by which an adult forms reproductive cells called gametes that contain half the number of chromosomes; this process is called _____________. Each gamete (egg or sperm in humans) will contain only one gene copy (one allele) for hemoglobin.
Fill in the following chart; use H= normal hemoglobin allele; h = sickle cell hemoglobin allele.
Adult phenotype |
Adult genotype |
Gametes Possible |
Normal hemoglobin |
|
|
Sickle cell hemoglobin |
|
|
Normal hemoglobin, carrier for sickle cell hemoglobin |
|
|
Genetic Crosses:
Do a genetic cross, using the Punnett square, of a sickle cell individual with a person who is homozygous normal. List genotypes and phenotypes of offspring.
Do a genetic cross (Punnett square) of two normal heterozygotes (carriers) of the sickle cell trait; list genotypes and phenotypes of offspring.
One note on the subtlety of genetic disease: in parts of Africa where malaria is very common and claims many lives, 20% of the population may be carriers for the sickle cell gene. Although being homozygous for sickle cell anemia leads to early death and lowered likelihood to pass on the gene, the sickle cell heterozygotes (carriers) in high-malaria regions have improved survivability over the homozygous normal individuals. Why? It turns out that red blood cells of individuals who are heterozygous for sickle cell are less easily infected by the malaria parasite, thus improving the heterozygous individual’s survival and ability to reproduce in that malaria-infested region. Hence the occurrence of the heterozygote is favored over the homozygous normal by selection pressures from the malaria parasite. What is the biologic lesson from this?
Genetic Testing and Counseling:
It is now possible to test people for the presence of the sickle cell hemoglobin. Testing can determine whether a person is homozygous normal or heterozygous normal (carrier) for sickle cell anemia. Sickle cell anemia is most frequent among African and Hispanic populations, and lower, but still present, among those of Italian, Greek, Arabian, Maltese, southern Asian, and Turkish ancestry.
Imagine that you are a genetic counselor and an African-American couple comes into the clinic and asks what is the likelihood that one of their children will have sickle cell anemia. They report no known family history of the disease; they both appear to have normal hemoglobin. No testing is done. You know that approximately one in ten African-Americans are carriers for the gene.
What are the possible genotypes for an individual who has the phenotype of normal hemoglobin: ____________ and _____________.
This couple, both of whom have normal hemoglobin phenotypes, could have sickle cell anemia offspring only if:
What is the overall risk for this couple, based on the incidence of the gene in the African-American population at large?
Do you think that people should be tested to see if they carry the gene? What are some pros and cons that you can think of for testing for the sickle cell gene? Make a chart:
PRO CON
Oklahoma is one of the states that currently screens newborns for sickle cell trait or disease. Check out this link to find out what other diseases the Oklahoma newborn screening program looks for:http://www.ok.gov/health/Child_and_Family_Health/Screening,_Special_Services_and_Sooner_Start/
Credits: From Mulvihill, C. (1996). Making the Chromosome-Gene-Protein Connection.
The American Biology Teacher, 58 (6), 364-368. With permission from the National Association of Biology Teachers.