Read from three generations, familial hypercholesterolemia proves autosomal dominant with a dose effect: one faulty LDL receptor allele halves clearance, and two nearly abolish it. Searches like "mn 551 unit 7 assignment example", "mn551 unit 7 sample" and "mn551 unit 7 example" land here.
One Allele or Two: A Three-Generation Pedigree Analysis of Familial Hypercholesterolemia With a Consanguineous Union
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Purdue University Global
MN551: Advanced Physiology and Pathophysiology
Unit 7 Assignment
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[Date]
The family is a composite built for teaching. No real family or patient is described.
The Pedigree
Figure 1 is drawn in standard notation (Bennett et al., 2008): squares for males, circles for females, filled symbols for affected members, a diagonal line for deceased members, and a double horizontal line for a consanguineous union. Untreated total cholesterol in mg/dL appears beneath each tested symbol. Members who were not tested are marked "not tested" and are not assumed to be unaffected. The founding couple above generation I, who were the parents of I-1 and I-3, are drawn from history only: their father died of a myocardial infarction at 49.
Generation I: I-1, male, 74, affected, 310. I-2, his wife, 71, unaffected, 185. I-3, female, sister of I-1, 70, affected, 295. I-4, her husband, deceased, not tested.
Generation II: children of I-1 and I-2 are II-1, female, 49, affected, 335; II-2, male, 46, unaffected, 190; and II-3, male, 43, affected, 320. II-4 is the husband of II-1, 51, unaffected, 200. Children of I-3 and I-4 are II-5, male, 45, unaffected, 175, and II-6, female, 41, affected, 285. II-3 and II-6 are first cousins and are married, shown by a double line.
Generation III: children of II-1 and II-4 are III-1, male, 22, affected, 270, and III-2, female, 19, unaffected, 170. Children of II-3 and II-6 are III-3, male, 10, affected, 265; III-4, female, 7, affected, 640, with tendon xanthomas over the extensor tendons of both hands; and III-5, female, 4, not tested.
Establishing the Transmission Pattern
Three observations fix the pattern. First, affected members appear in every generation: I-1 and I-3 in generation I, II-1, II-3 and II-6 in generation II, and III-1, III-3 and III-4 in generation III. The trait does not skip, which is what a dominant allele produces when every carrier expresses it. Second, I-1 passed the condition to his son II-3, and a father cannot transmit an X-linked allele to a son, so father-to-son transmission excludes X-linked inheritance in a single observation. Third, about half of each affected parent's children are affected: two of three for I-1, one of two for I-3, one of two for II-1. With families this small the proportions are approximate, but they sit where a dominant allele predicts, and males and females are affected in similar numbers.
A recessive pattern would require unaffected carrier parents to produce affected children, and in this family every affected child except one has an affected parent on one side only. That exception, III-4, is the most informative person on the chart. Her parents are both affected, her values are extreme, and her place in a consanguineous branch is exactly where a second copy of a rare allele would be expected to appear if the pattern is dominant with a dose effect.
Explaining the Severe Child
III-4 is not simply a severe case of the family's condition. Her total cholesterol of 640 mg/dL is roughly double the range of her affected relatives, whose values cluster between 265 and 335, and she already has tendon xanthomas at age seven. Her parents are both affected: II-3 is the son of I-1, and II-6 is the daughter of I-3. Because I-1 and I-3 are siblings who each carry the allele, and both inherited it from their father, II-3 and II-6 can carry the same allele descended from one ancestor. Each passed one copy to III-4, who is homozygous.
This is what a semidominant allele looks like. One working copy produces roughly half the normal amount of functional protein, and the heterozygote is clearly affected. Two nonfunctional copies leave almost none, and the phenotype is not the same condition made slightly worse but a different order of severity (Sturm et al., 2018). The consanguineous loop is the reason this family shows both forms. Without it, the chance that two carriers of the same rare allele would marry is small; with it, the allele meets itself.
From Genotype to Receptor Count
The gene in this family encodes the LDL receptor. Hepatocytes display these receptors in clathrin-coated pits on their surface. Circulating LDL binds through apolipoprotein B-100, the pit invaginates, and the receptor-LDL complex enters the cell by endocytosis. In the acidic endosome the LDL is released and sent to lysosomes, where its cholesterol is freed for cellular use, and the receptor returns to the surface to bind again, cycling many times during its life (Goldstein & Brown, 2009).
Clearance of LDL from plasma depends on how many working receptors are on the surface. A heterozygote such as II-3 has about half the normal number, so LDL is removed at about half the normal rate and accumulates until the plasma level rises enough that clearance again matches production. That new steady state is roughly double normal, which fits the values of 265 to 335 in generations I through III. III-4 has almost no functional receptors, so clearance by this route nearly stops and plasma LDL rises several-fold. The pedigree predicts the laboratory values once genotype is converted to receptor number.
Cholesterol that is not cleared by the liver does not stay in the blood indefinitely. LDL crosses into the arterial intima and tendon sheaths, is oxidized, and is taken up by macrophages through scavenger receptors that, unlike the LDL receptor, are not downregulated when the cell is full. The macrophages become foam cells. In III-4 this process has already produced visible xanthomas over her knuckle tendons, and the same process is building plaque in her arterial walls (Rogers, 2023). Her nodules are a direct consequence of the number beneath her symbol.
The pedigree also explains why the heterozygous values vary. II-1 sits at 335 while III-3 sits at 265, although both carry one affected allele. Receptor number sets the main clearance rate, but diet, age, body weight and other genes that influence LDL production and clearance move the steady state within the heterozygous range. Age matters most in this family: the three lowest heterozygous values belong to the youngest carriers, and cholesterol rises with age in carriers as in everyone else. The variation within the heterozygous cluster is small compared with the gap between that cluster and III-4, which is why the dose effect remains clear despite it.
Risk for Future Children of II-3 and II-6
Both parents are heterozygous. Each passes either the affected allele or the normal allele with equal probability, and the two events are independent. For each future child, the probability of receiving two affected alleles is 1/2 x 1/2 = 1/4; of receiving exactly one, 2 x 1/2 x 1/2 = 1/2; and of receiving none, 1/4. Three of every four children of this couple would therefore be expected to carry at least one affected allele. The probability applies to each pregnancy separately. The fact that III-4 is already homozygous does not change the chance for the next child, and III-5, now four and untested, carries the same prior probabilities until her cholesterol is measured.
References
Bennett, R. L., French, K. S., Resta, R. G., & Doyle, D. L. (2008). Standardized human pedigree nomenclature: Update and assessment of the recommendations of the National Society of Genetic Counselors. Journal of Genetic Counseling, 17(5), 424-433. https://doi.org/10.1007/s10897-008-9169-9
Goldstein, J. L., & Brown, M. S. (2009). The LDL receptor. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(4), 431-438. https://doi.org/10.1161/ATVBAHA.108.179564
Rogers, J. L. (Ed.). (2023). McCance and Huether's pathophysiology: The biologic basis for disease in adults and children (9th ed.). Elsevier.
Sturm, A. C., Knowles, J. W., Gidding, S. S., Ahmad, Z. S., Ahmed, C. D., Ballantyne, C. M., Baum, S. J., Bourbon, M., Carrié, A., Cuchel, M., de Ferranti, S. D., Defesche, J. C., Freiberger, T., Hershberger, R. E., Hovingh, G. K., Karayan, L., Kastelein, J. J. P., Kindt, I., Lane, S. R., ... Rader, D. J. (2018). Clinical genetic testing for familial hypercholesterolemia: JACC Scientific Expert Panel. Journal of the American College of Cardiology, 72(6), 662-680. https://doi.org/10.1016/j.jacc.2018.05.044
How this MN551 Unit 7 example is structured
Pattern comes first, mechanism second, and a short probability section third, so the analysis moves from what the family shows to why and then to what it predicts. Each inference cites a numbered individual, II-3 or III-5, so the grader can check it against the chart. The dose effect is argued rather than asserted: heterozygous members cluster between 250 and 400 mg/dL, the homozygous child sits far above them, and that step is what a semidominant allele produces when one working copy yields roughly half the protein. The receptor paragraph follows LDL from the bloodstream to coated pits, endocytosis and receptor recycling, then shows what halving receptor number does to plasma levels. In the probability section, each future child of the cousin couple carries a one-in-four chance of two affected alleles, computed and stated as a fraction.
Get an MN551 Unit 7 example written to your instructions
Whatever family history your MN551 Unit 7 prompt supplies, hand it over with the instructions and rubric. One analysis is free to start, shaped by those documents and returned in 24-48h: the pattern argued from named individuals, the mechanism tied to what the allele does in the cell, and the probabilities worked as fractions. The paper above is an original model document written by our desk, not a submitted student paper and not an official Purdue University Global document.
MN551 Unit 7 questions, answered
What if the pedigree shows a recessive condition?
The same pairing of pattern and mechanism applies. A recessive chart typically skips generations and shows affected children of unaffected parents, often with consanguinity. The mechanism section then explains why one working copy is enough, usually because half the enzyme or protein still meets demand, which is the opposite of the dose effect seen in this sample.
Does the analysis need a Punnett square?
Only where the prompt asks for probabilities. The sample shows one for the cousin couple's future children because recurrence risk arises there. Elsewhere the chart itself carries the reasoning, and a Punnett square for every mating tends to fill pages without adding an argument the grader can credit.
Should genetic testing or counseling be discussed?
Only if the prompt raises it. In a pathophysiology course the weight sits on transmission and mechanism, and testing usually earns a sentence at most, noting what a confirmed variant would add. A section on counseling practice or screening policy, however careful, answers a question from a different course and costs space the mechanism needed.