Pedigree Reasoning for an Inherited Trait
A biology student studying a family in a village near Mazar-i-Sharif records the following: Parents I-1 (father) and I-2 (mother) are both unaffected by a certain trait. They have three children: II-1 (son, affected), II-2 (daughter, unaffected), and II-3 (daughter, affected). The affected son II-1 marries an unaffected woman II-4, and they have an affected daughter III-1 and an unaffected son III-2. No one in the extended family has any other known disorder, and the trait appears in every generation where an affected person has children with an unaffected partner. The student must decide whether the trait is autosomal dominant, autosomal recessive, or X-linked recessive, and justify the choice.
1. Determine the most likely mode of inheritance and justify it using the pedigree.
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Key observation: unaffected parents I-1 and I-2 have affected children (II-1 and II-3). This rules out autosomal dominant, because a dominant trait cannot appear in a child unless at least one parent carries and expresses it. It also rules out X-linked dominant for the same reason.
So the trait is recessive. To distinguish autosomal recessive from X-linked recessive, look at II-3, an affected daughter. An affected daughter under X-linked recessive would need an affected father (she must inherit a recessive allele on the X from each parent, and the father has only one X). But father I-1 is unaffected, so X-linked recessive is ruled out.
Therefore the trait is autosomal recessive: both parents are heterozygous carriers (Aa x Aa), and affected children are aa.
2. Using your conclusion, assign genotypes to I-1, I-2, II-1, and II-3, and explain the probability that a fourth child of I-1 and I-2 would be affected.
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Let A = normal allele, a = affected allele. I-1: Aa (unaffected carrier). I-2: Aa (unaffected carrier). II-1 (affected son): aa. II-3 (affected daughter): aa.
Cross Aa x Aa gives offspring genotypes in ratio 1 AA : 2 Aa : 1 aa. The probability of an affected child (aa) is 1/4 = 25 percent, independent of the sexes of previous children.
3. II-1 (aa) marries II-4, an unaffected woman from outside the family. They have an affected daughter III-1. What must II-4's genotype be, and what does this tell you about the frequency of the allele in the population?
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II-1 is aa, so he passes an 'a' to every child. For daughter III-1 to be affected (aa), she must receive an 'a' from her mother II-4 as well. Since II-4 is unaffected, she must be a carrier: Aa.
This means II-4, who married in from outside, carries the recessive allele. That implies the allele is not extremely rare in the population - carriers (Aa) must be reasonably common, because an outsider marrying in happened to be a carrier. This is consistent with a recessive allele maintained at appreciable frequency, and it warns against assuming outsiders are homozygous normal when counseling families.