Passage
Abnormal blood lipid levels play a significant role in the development of coronary artery disease (CAD) . The discovery of genomic variations that confer a protective effect against CAD has prompted investigations into the biological impact of these protective alleles. Researchers have observed that specific single-base variations in the ANGPTL4 gene are common among patients with a low occurrence of CAD. ANGPTL4 is located on chromosome 19 and codes for angiopoietin-like 4, a multifunctional glycosylated protein.One of the functions of angiopoietin-like 4 is the regulation of lipid metabolism. The N-terminal domain of angiopoietin-like 4 induces a conformational change in the enzyme lipoprotein lipase (LPL) , forcing the LPL homodimer to dissociate into two inactive 225-residue monomers. LPL functions on the surface of vascular endothelial cells and degrades the triglycerides of chylomicrons and very-low-density lipoproteins (VLDLs) in the blood. Elevated triglyceride levels have been correlated with increased CAD risk.To identify common loss-of-function mutations in ANGPTL4, DNA samples from 43,000 individuals with CAD and 78,000 individuals without CAD were genotyped. A detailed analysis of ANGPTL4 genomic variants was performed, and the results of individuals without CAD were mapped in Figure 1. The lipid profiles of ANGPTL4 mutation noncarriers were also compared to those of mutation carriers (Figure 2) .
Figure 1 Loss-of-function mutations observed in ANGPTL4 in participants without CAD (Note: * = mutation resulting in a truncated protein; † = substitution of a cytosine for its complementary base.)
Figure 2 Mean plasma lipid levels for ANGPTL4 mutation carriers and noncarriers (Note: LDL = low-density lipoprotein; HDL = high-density lipoprotein; error bars = standard deviation.) To further analyze the effect of ANGPTL4 on blood lipid levels, ANGPTL4 knockout mice and mice that constitutively express ANGPTL4 were created. Researchers hypothesized that two of the four biological profiles shown in Table 1 would be observed in these mice.Table 1 Predicted Biological Profiles of ANGPTL4 Mouse Models

-Based on Figure 1, which of the following nucleotides would cause the T291-1 loss-of-function mutation if it were substituted for cytosine?

Question

Passage
Abnormal blood lipid levels play a significant role in the development of coronary artery disease (CAD) . The discovery of genomic variations that confer a protective effect against CAD has prompted investigations into the biological impact of these protective alleles. Researchers have observed that specific single-base variations in the ANGPTL4 gene are common among patients with a low occurrence of CAD. ANGPTL4 is located on chromosome 19 and codes for angiopoietin-like 4, a multifunctional glycosylated protein.One of the functions of angiopoietin-like 4 is the regulation of lipid metabolism. The N-terminal domain of angiopoietin-like 4 induces a conformational change in the enzyme lipoprotein lipase (LPL) , forcing the LPL homodimer to dissociate into two inactive 225-residue monomers. LPL functions on the surface of vascular endothelial cells and degrades the triglycerides of chylomicrons and very-low-density lipoproteins (VLDLs) in the blood. Elevated triglyceride levels have been correlated with increased CAD risk.To identify common loss-of-function mutations in ANGPTL4, DNA samples from 43,000 individuals with CAD and 78,000 individuals without CAD were genotyped. A detailed analysis of ANGPTL4 genomic variants was performed, and the results of individuals without CAD were mapped in Figure 1. The lipid profiles of ANGPTL4 mutation noncarriers were also compared to those of mutation carriers (Figure 2) .

Figure 1 Loss-of-function mutations observed in ANGPTL4 in participants without CAD (Note: * = mutation resulting in a truncated protein; † = substitution of a cytosine for its complementary base.)

Figure 2 Mean plasma lipid levels for ANGPTL4 mutation carriers and noncarriers (Note: LDL = low-density lipoprotein; HDL = high-density lipoprotein; error bars = standard deviation.) To further analyze the effect of ANGPTL4 on blood lipid levels, ANGPTL4 knockout mice and mice that constitutively express ANGPTL4 were created. Researchers hypothesized that two of the four biological profiles shown in Table 1 would be observed in these mice.Table 1 Predicted Biological Profiles of ANGPTL4 Mouse Models

-Based on Figure 1, which of the following nucleotides would cause the T291-1 loss-of-function mutation if it were substituted for cytosine?

Quizplus · Accepted Answer

11ecba2d_0feb_d16e_a3bf_ed52a327dea7_MD0008_00 Deoxyribonucleotides, the building blocks of DNA, are each composed of a phosphate, a deoxyribose sugar, and one of four nitrogenous bases (A, T, C, or G). Individual nucleotides can be identified by analyzing the structure of their attached base: Cytosine (C) and thymine (T) are one-ringed bases known as pyrimidines. Thymine contains a methyl group (-CH₃) attached to the carbon atom in the fifth position, a feature that helps distinguish it from cytosine. Guanine (G) and adenine (A) are two-ringed bases known as purines. Guanine has a carbonyl group (-C=O) at the sixth position that helps differentiate it from adenine. In double-stranded genetic material, complementary base pairing is the bonding of a particular nucleotide with only one other type of nucleotide. Such base pairing is determined by the alignment of the hydrogen bond donors and acceptors of each nucleotide's nitrogenous base. Cytosine and guanine always base pair via three hydrogen bonds. The caption for Figure 1 states that the T291-1 mutation in ANGPTL4 results after substituting a cytosine with its complementary base (guanine), which is depicted in Choice B. (Choice A) The nucleotide here contains an adenine base, which is complementary to thymine (not cytosine). In DNA, adenine always base pairs with thymine via two hydrogen bonds. In RNA, adenine base pairs with uracil (U). (Choices C and D) These nucleotides contain a ribose sugar with a hydroxyl group (-OH) on the 2′ and 3′ carbon atoms. Therefore, these are ribonucleotides found in RNA (not deoxyribonucleotides found in DNA). Educational objective: Deoxyribonucleotides are composed of a phosphate, a deoxyribose sugar, and a nitrogenous base (A, T, C, or G). Cytosine and thymine are pyrimidines (single-ringed bases) whereas guanine and adenine are purines (double-ringed bases). In double-stranded DNA, cytosine always aligns with guanine (and vice versa), and adenine always aligns with thymine (and vice versa) via complementary base pairing.

Passage Abnormal Blood Lipid Levels Play a Significant Role in the the Development