"Sickle cell anemia: tracking down a mutation": an interactive learning laboratory that communicates basic principles of genetics and cellular biology

Abstract

"Sickle cell anemia: tracking down a mutation" is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients have the sickle cell genotype/phenotype using DNA and blood samples from wild-type and transgenic mice that carry a sickle cell mutation. The inquiry-based, problem-solving approach facilitates the students' understanding of the basic concepts of genetics and cellular and molecular biology and provides experience with contemporary tools of biotechnology. It also leads to students' appreciation of the causes and consequences of this genetic disease, which is relatively common in individuals of African descent, and increases their understanding of the first principles of genetics. This protocol provides optimal learning when led by well-trained facilitators (including the classroom teacher) and carried out in small groups (6:1 student-to-teacher ratio). This high-quality experience can be offered to a large number of students at a relatively low cost, and it is especially effective in collaboration with a local science museum and/or university. Over the past 15 yr, >12,000 students have completed this inquiry-based learning experience and demonstrated a consistent, substantial increase in their understanding of the disease and genetics in general.

Keywords: cellulose acetate; genetics; inquiry-based learning; restriction digest; sickle cell.

Fig. 1.

A: atypical agarose gel photo micrographic image of digested DNA from normal, homozygous, and heterozygous sickle cell samples. See B for further details. Lane 1, 100-bp DNA marker; lane 2, empty; lane 3, sample X uncut; lane 4, sample X cut; lane 5, sample Y uncut; lane 6, sample Y cut; lane 7, sample Z uncut; lane 8, sample Z cut. B: a demonstration mockup of ideal results of the sickle cell agarose gel electrophoresis in the experience. The green fill demonstrates the slow migration of the uncut DNA. In control (unaffected) individuals, the DNA is cut by the restriction enzyme (Bsu36I) and splits into two bands (blue). The lack of an enzyme site in the homozygous sickle cell patient blocks the ability of Bsu36I to cut the DNA, and, therefore, only one green band appears. In heterozygous carriers, both the uncut and cut band appear, indicating that the individual has both unaffected (green) and affected (blue) DNA. Lane 1, 100-bp DNA marker, lane 2, empty; lane 3, sample X uncut; lane 4, sample X cut; lane 5, sample Y uncut; lane 6, sample Y cut; lane 7, sample Z uncut; lane 8, sample Z cut.

Fig. 2.

Pre- and posttest scores (percent correct) for high school students taking this module of GENEius during the 2004–2011 school years (n = 18,128). See the test instrument in the Supplemental Material appendix 2.