Exam 10: The Integration of Genetic Approaches: Understanding Sickle Cell Disease

Given what you know of the inheritance pattern of SCD, is the following pedigree representative of a typical SCD pedigree?

Given the following gel, which DNA fragment has a lower electrophoretic mobility?

You are interested in designing a molecular probe to detect the region of β^S SNP, which includes a DdeI (CTNAG)restriction site. Which of the following molecular probe sequences would anneal to the correct position?

Being a carrier of the sickle cell trait, although generally not a serious problem, can pose significant risks for athletes, particularly those in intense training regimens. The death of Florida State University linebacker Devaughn Darling, a carrier of the sickle cell trait, in a spring conditioning drill refocused attention on sickle cell abnormalities, including both sickle cell disease and sickle cell trait (carriers). High altitude, aggressive exercise, and high temperatures can all lead to acute rhabdomyolysis in individuals with sickle cell trait. Why do you think an individual who is a carrier of the sickle cell trait may be more likely to experience the symptoms of SCD during rigorous exercise?

As part of the maturation process, red blood cells lose their nucleus. What is the consequence for cell division in these cells?

Can Southern and northern blotting detect differences between WT and mutant β-globin gene or between WT and mRNA or both? A)Only differences between WT and the gene can be detected. B)Only differences between WT and the mRNA can be detected. C)Differences between the WT and both the gene and the mRNA can be detected. D)Neither differences between WT and the gene nor between WT and the mRNA can be detected.

Globin genes contain ________ segments that ultimately encode the amino acids of the protein and interspersed ________ sequences that do not contribute to encoding the protein product of the gene.

Hemoglobin is made up of four proteins from two different gene clusters, the α-globin gene cluster and the β-globin gene cluster. The two clusters are related, having evolved from a common ancestral gene through gene duplication, based on strong similarities in which three gene characteristics?

A SNP results in a loss of the XhoI site indicated in the bacterial plasmid below. You design a molecular probe that spans the lost XhoI site. Which lane represents the expected Southern blot of a bacterial cell that carries two copies of the plasmid: a normal version and the version with the lost XhoI site?

Which of the following techniques describes either the rate of a molecule's migration or its final position in a gel?

Sodium dodecyl sulfate (SDS)is a detergent commonly added to protein samples before gel electrophoresis. The purpose of the negatively charged SDS is to neutralize the charges and denature the protein to remove secondary structures. Thus, the proteins can be separated on a gel based solely on what parameter?

Given the following plasmid, what are the sizes of the fragments you would expect from a NotI digest?

Two probes, A and B, hybridize very near each other in a region of DNA that contains RFLPs when digested with HindIII. The four maps show the location and intervening distances of the HindIII restriction sites and the binding locations of probes A and B. The maps show alleles H¹-H⁴ present in a population. What band(s)is/are seen in Southern blot analysis of a H²H³ heterozygote using probe B?

Hemoglobin, the protein responsible for binding and transporting oxygen, forms a tetramer. What is the protein composition of the most common form of hemoglobin, hemoglobin A (HbA)?

In contrast to the nucleic acid probes used to detect DNA or RNA target sequences, molecular probes used to detect target proteins in western blots are ________.

Northern blotting is not useful in detecting the SNPs associated with the β^A and β^S alleles. Explain why.

A restriction map of β^A and β^S is shown. Members of a family were analyzed by cutting their DNA with DdeI. Which individuals in the family have the genotype β^Aβ^A?

We can detect the SNP in the β^S allele because it destroys a DdeI restriction site, leading to DNA restriction fragment variation revealed by Southern blot analysis. Either two or three restriction sequences for the restriction endonuclease DdeI can occur near the β-globin gene, depending on the allele. One DdeI restriction sequence is eliminated from the β^S allele by the SNP in the mutant allele because of a mutation in the double-stranded target sequence 5′ - CTNAG - 3′. Suppose the wild-type allele sequence is CCTGAG, while a newly identified SNP is CCTTAG. Would this same restriction fragment analysis technique be appropriate for detecting this particular SNP? What other technique(s)could you use to identify this particular mutation?

The rate of molecule movement in electrophoretic gels depends on three parameters of molecular structure. Each of these parameters individually is important in determining how a particular molecule migrates, but they can also interact with one another to produce a characteristic migration rate for each molecule. What are the three parameters?

At a biological level, β^Aβ^S heterozygotes suffer fewer cases of malaria than β^Aβ^A homozygotes, and when they do get malaria, their disease is less severe. What is the biological explanation for the heterozygous advantage?