Gene Therapy and Transgenic Animals

Gene therapy now offers potential cures for individuals with inherited diseases. The initial goal is to introduce a normal copy of the gene that is defective into the tissues that give rise to the pathology of the genetic disease. For instance, about 50 of the children with severe combined immunodeficiency have a mutation in the gene encoding the y chain common to several of the interleukin receptors. Recently, cDNA from a normal y-chain gene was used to transduce autologous cells from infants...

Type IIA Hypercholesterolemia LDL Receptor Deficiency

This is a dominant genetic disease affecting 1 500 (heterozygous) individuals in the United States. It is characterized by elevated LDL cholesterol and increased risk for atherosclerosis and coronary artery disease. Cholesterol deposits may be seen as Xanthomas of the Achilles tendon Subcutaneous tuberous xanthomas over the elbows Xanthelasma (lipid in the eyelid) Homozygous individuals (1 106) often have myocardial infarctions before 20 years of age. Regulation of Cholesterol Level in...

Info

A 9-week-old boy, healthy at birth, begins to develop symptoms of ketoacidosis, vomiting, lethargy, seizures and hypertonia. Urine has characteristic odor of maple syrup. 11. A child with white-blond hair, blue eyes, and pale complexion is on a special diet in which one of the essential amino acids is severely restricted. He has been told to avoid foods artificially sweetened with aspartame. 12. A chronically ill patient on long-term (home) parenteral nutrition develops metabolic acidosis,...

Answers

The 3' to 5' exonuclease activity of DNA pol 8 represents the proofreading activity of an enzyme required for the replication of human chromosomal DNA. DNA pol y (mitochondrial) and DNA pol III (prokaryotic) do not participate in this process, short RNA primers are replaced with DNA during replication, and new DNA strands are always synthesized in the 5' to 3' direction. Answer e. TBP and CBP participate in eukaryotic gene transcription and mRNA translation, respectively. CAP...

Table of Contents

Section I Molecular Biology and Biochemistry Chapter 1 Nucleic Acid Structure and Organization 3 Chapter 2 DNA Replication and Repair 15 Chapter 3 Transcription and RNA Processing 27 Chapter 4 The Genetic Code, Mutations, and Translation 43 Chapter 5 Genetic Regulation Chapter 6 Recombinant Chapter 7 Genetic Testing Chapter 8 Amino Acids, Proteins, and Enzymes 117 Chapter 9 Hormones Chapter 10 Chapter 11 Overview of Energy Chapter 12 Glycolysis and Pyruvate Dehydrogenase 161 Chapter 13 Citric...

Citrate Shuttle and Malic Enzyme

The citrate shuttle transports acetyl CoA groups from the mitochondria to the cytoplasm for fatty acid synthesis. Acetyl CoA combines with oxaloacetate in the mitochondria to form citrate, but rather than continuing in the citric acid cycle, citrate is transported into the cytoplasm. Factors that indirectly promote this process include insulin and high-energy status. In the cytoplasm, citrate lyase splits citrate back into acetyl CoA and oxaloacetate. The oxaloacetate returns to the...

Review Questions

A patient with manic depressive disorder is treated with lithium, which slows the turnover of inositol phosphates and the phosphatidyl inositol derivatives in cells. Which of the following protein kinases is most directly affected by this drug Tumor cells from a person with leukemia have been analyzed to determine which oncogene is involved in the transformation. After partial sequencing of the gene, the predicted gene product is identified as a tyrosine kinase. 2. Which of the following...

Chylomicrons VLDL and Idl Vldl Remnants

Chylomicrons and VLDL are primarily triglyceride particles, although they each have small quantities of cholesterol esters. Chylomicrons transport dietary triglyceride to adipose tissue and muscle, whereas VLDL transport triglyceride synthesized in the liver to these same tissues. Both chylomicrons and VLDL have apoC-II, apoE, and apoB (apoB-48 on chylomicrons and apoB-100 on VLDL). The metabolism of these particles is shown in Figure 1-15-5. Figure 1-15-5. Chylomicron and VLDL Metabolism...

Wobble

Wobble arid Protein Synthesis Protein synthesis occurs by peptide bond formation between successive amino acids whose order is specified by a gene and thus by an mRNA. The formation of a peptide bond between the car-boxyl group on one amino acid and the amjno group of another is illustrated in Figure 1-4-7. J I T I I 1 Figure 1-4-7. Peptide Bond Formation During translation, the amino acids are attached to the 3' ends of their respective tRNAs. The amino acyl-tRNAs are situated in...

Functional Relationship of Glucagon and Insulin

Insulin, associated with well-fed, absorptive metabolism, and glucagon, associated with fasting and post absorptive metabolism, usually oppose each other with respect to pathways of energy metabolism. Glucagon works through the cAMP system to activate protein kinase A favoring phosphorylation of rate-limiting enzymes, whereas insulin often activates protein phosphatases that dephosphorylate many of the same enzymes. An example of this opposition in glycogen metabolism is shown in Figure 1-9-5....

Glucose 6Phosphate Dehydrogenase Deficiency

Deficiency of G5PDH may result in hemolytic anemia and, in rare cases, symptoms resembling chronic granulomatous disease (CGD). The disease shows significant allelic heterogeneity (over 400 different mutations in tile G6PDH gene are known). The major symptom is either an acute episodic or (rarely) a chronic hemolysis. The disease is X-linked recessive. Female heterozygous for G6PDH deficiency have increased resistance to malaria. Consequently, the deficiency is seen more commonly in families...

Control of Gluconeogenesis by Response Elements

Cortisol and Glucagon Stimulate Gluconeogenesis Through Enhancer Mechanisms An example of how response elements affect metabolism can be seen in the pathway of gluconeogenesis (Figure 1-5-6). Gluconeogenesis is a hepatic pathway whose major function is to maintain adequate glucose in the blood for tissues like the nerves (brain) and red blood cells during fasting. It also provides glucose during periods of stress. Hormones that activate the pathway include Glucagon secreted in...

Carrier Detection and Prenatal Diagnosis of Sickle Cell Disease

Figure 1-7-9 shows the pedigree of a family in which the autosomal recessive disorder sickle cell disease is segregating. The father and mother are both carriers, and they have produced an affected son. Ms ill restriction maps of die normal A and mutant S 5-globin genes and Southern blots from each member of the family are also given. The probe used binds to the 5' flanking region. Several types of repetitive sequences have been identified in chromosomes. Generally, but not always, these are...

RFLP Diagnosis of Myotonic Dystrophy

Southern Blot Myotonic Dystrophy

With the advent of the polymerase chain reaction PCR , faster, more-sensitive tests have been developed, and therefore Southern blots have largely been replaced by these PCR-based tests in clinical practice. RPLP analysis is still useful in a few cases in which polymorphisms are too large to conveniently amplify with a PCR. One such case is myotonic dystrophy, in which the expanded sequence is within the gene region itself a CTG in the 3' untranslated region UTR . This disease shows...