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Tamarin: Principles of Genetics, Seventh Edition
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II. Mendelism and the Chromosomal Theory
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5. Sex Determination, Sex Linkage, and Pedigree Analysis
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In no place in the pedigree is the trait passed from father to son. This would defy the route of an affected X chromosome.We can conclude from the pedigree that hemophilia is a sex-linked recessive trait. (Several different inherited forms of hemophilia are known, each de cient in one of the steps in the pathway that forms brinogen, the blood clot protein. Two of these forms, classic hemophilia A and hemophilia B, also called Christmas disease, are sex linked. Other hemophilias are autosomal.) One other interesting point about this pedigree is that there is no evidence of the disease in Queen Victoria s ancestors, yet she was obviously a heterozygote, having one affected son and two daughters who were known carriers. Thus, though she was born to what appears to be a homozygous normal mother and a hemizygous normal father, one of Queen Victoria s X chromosomes had the hemophilia allele. This could have happened if a change (mutation) had occurred in one of the gametes that formed Queen Victoria. ( We explore the mechanisms of mutation in chapter 12.) Figure 5.23 is another pedigree that points to dominant inheritance because the trait skips no generations. The pedigree shows the distribution of low bloodphosphorus levels, the fully penetrant aspect of vitaminD-resistant rickets, among the sexes. Affected males pass on the trait to their daughters but not their sons. This pattern follows that of the X chromosome: a male passes it on to all of his daughters but to none of his sons. Although this pedigree accords with a sex-linked dominant mode of inheritance, it does not rule out autosomal inheritance. The pedigree shown is a small part of one involving hundreds of people, all with phenotypes consistent with the hypothesis of sex-linked dominant inheritance. In gure 5.23, there is the slight possibility that the trait is recessive. This could be true if the male in generation I and the mates of II-5 and II-7 were all heterozygotes. Since this is a rare trait, the possibility that all these conditions occurred is small. For example, if one person in fty (0.02) is a heterozygote, then the probability of three heterozygotes mating within the same pedigree is (0.02)3, or eight in one million. The rareness of this event further supports the hypothesis of dominant inheritance. The expected patterns for the various types of inheritance in pedigrees can be summarized in the following four categories: Autosomal Recessive Inheritance 1. Trait often skips generations. 2. An almost equal number of affected males and females occur. 3. Traits are often found in pedigrees with consanguineous matings. 4. If both parents are affected, all children should be affected.
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5. In most cases when unaffected people mate with affected individuals, all children are unaffected. When at least one child is affected (indicating that the unaffected parent is heterozygous), approximately half the children should be affected. 6. Most affected individuals have unaffected parents. Autosomal Dominant Inheritance 1. Trait should not skip generations (unless trait lacks full penetrance). 2. When an affected person mates with an unaffected person, approximately 50% of their offspring should be affected (indicating also that the affected individual is heterozygous). 3. The trait should appear in almost equal numbers among the sexes. Sex-Linked Recessive Inheritance 1. Most affected individuals are male. 2. Affected males result from mothers who are affected or who are known to be carriers (heterozygotes) because they have affected brothers, fathers, or maternal uncles. 3. Affected females come from affected fathers and affected or carrier mothers. 4. The sons of affected females should be affected. 5. Approximately half the sons of carrier females should be affected. Sex-Linked Dominant Inheritance 1. The trait does not skip generations. 2. Affected males must come from affected mothers. 3. Approximately half the children of an affected heterozygous female are affected. 4. Affected females come from affected mothers or fathers. 5. All the daughters, but none of the sons, of an affected father are affected.
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Part of a pedigree of vitamin-D-resistant rickets. Affected individuals have low blood-phosphorus levels. Although the sample is too small for certainty, dominance is indicated because every generation was affected, and sex linkage is suggested by the distribution of affected individuals.
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