QUESTIONS AT THE BOTTOM: Hemoglobin is an iron-containing protein in red blood cells that transports oxygen from the lungs to cells throughout the body. Hemoglobin is a protein complex that is composed of four polypeptide subunits. Typically, two of the polypeptide subunits are called beta-globin subunits. Each globin subunit contains a single iron atom capable of binding oxygen.
Prior to birth and during early infancy, expression of the HBB gene is low and, instead, cells produce a third polypeptide called gamma-globin. During this time, the hemoglobin complex consists of two alpha-globin subunits and two gamma-globin subunits and is referred to as a fetal hemoglobin. Fetal hemoglobin is able to bind oxygen more tightly than does the typical adult hemoglobin, which enables the fetus (unborn offspring) to remove oxygen from the hemoglobin in the mother’s blood. A model of the expression levels of all three types of globin polypeptides during the weeks leading up to the following birth is shown in Figure 1. (Will attach pics at the bottom in chronological order from Figure 1-Figure 3)
Mutations in the genes that encode globin subunits may affect the function of hemoglobin. Beta-thalassemia is an inherited disorder that results from a variety of mutations to the HBB gene that encodes the beta-globin subunit. The incidence of beta-thalassemia in one particular family is shown in Figure 2.
The inability to produce functional beta-globin results in an imbalance of alpha and beta-globin subunits. The accumulation of free alpha-globin subunits causes red blood cells to lyse (burst) or undergo apoptosis (Figure 3). The extra alpha-globin subunits are unable to correctly fold into a hemoglobin protein complex and instead form structures called alpa-hemichromes. The alpha-hemichromes are then depostied in a solid form on the surface of the red blood cells, causing the red blood cells to lyse. Figure 3.
(a) Based on the pedigree shown in Figure 2, describe the HBB alleles inherited by individual 11, including the parent from which each allele came.
(b) Explain how mutant hemoglobin interferes with a cell’s ability to synthesize ATP. Red blood cells damaged by the accumulation of alpha-hemichromes undergo apoptosis and are taken into other cells by a process similar to endocytosis. Explain how these cells will digest and recycle the components of the apoptotic red blood cells.
(c) While studying the family shown in the pedigree shown in Figure 2, researchers notice that HBB mutant allele and an allele for another trait are passed on together at a frequency greater than that which would be predicted if the genes assorted independently. Predict the cause of this increased frequency of inheritance. Justify your prediction.
(d) A researcher claims that HBB exhibits a maternal mitochondrial inheritance pattern. Use the pedigree to refute the researcher’s claim.