Pedigree patterns

Figure 1. Pedigree pattern of the B family. Relationship of the proband (T.B.) with the clinical phenotype of homozygous familial hypercholesterolemia to her other relatives whom we studied is shown. Lipoprotein patterns were determined after ultracentrifugation using NIH outpoints (51). F indicates that fibroblast cell lines were established from skin biopsies. Males, H Females, O.

Characteristics of X-linked recessive diseases include an oblique pedigree pattern, affliction of males only, frequent female carriers, and a 25% recurrence risk for carrier females (see pedigree C on chart). Corollary Haldane s law predicts a 2/3 chance that the mother of an affected male with X-linked recessive disease is a carrier (and a 1/3 chance the affected male represents a new mutation). 

A 10-year-old girl is diagnosed with Marfan syndrome, an autosomal dominant condition. An extensive review of her pedigree indicates no previous family history of this disorder. The most likely explanation for this pattern is... 

Marfan syndrome is an excelient example of pleiotropy (choice E), but this principle refers to the fact that a single mutation can affect multiple aspects of the phenotype, so it would not explain the pattern observed in this pedigree. 

Figure 13-1. Definitions of symbols used to evaluate inheritance patterns for pedigree analysis and relationships within kindreds. Generations are assigned Roman numerals and individuals within each generation are indicated by Arabic numerals. The arrow points at the proband, the person in whom the genetic disorder was first diagnosed.

Figure 13-2. Pedigrees illustrating autosomal inheritance patterns. Recessive inheritance is shown in pedigrees A and B. Note that consanguinity in pedigree B reinforces the hypothesis of an autosomal recessive disorder. Dominant inheritance is shown in pedigree C, in which every affected person has an affected parent.

Figure 13-3. Pedigrees illustrating X-linked recessive (A) and dominant (B) inheritance patterns. Note the absence of male-to-male transmission in both pedigrees and the predominance of affected males over females in the X-linked recessive pedigree.

Figure 13-4. Pedigrees illustrating inheritance of (A) a mitochondrial disorder and (B) an autosomal dominant disorder exhibiting anticipation. In pedigree A note the similarity to the X-linked dominant inheritance pattern (Figure 13-3A), but incomplete penetrance as exemplified by individuals 11-4 and 111-4. In pedigree B, the age of onset, indicated next to the symbols for affected individuals, becomes progressively earlier with each generation.

The following pedigree shows the pattern of inheritance of a neurologic disorder in a large Central American kindred. Note that the numbers above symbols representing affected persons in this pedigree indicate age of diagnosis. 

The answer is B. The clinical symptoms in this case strongly suggest a mitochondrial disorder affecting both neurologic and musculoskeletal functions. In such cases, no male-to-male transmission is possible because the mother s ovum provides all the cytoplasmic components, including the mitochondria, for the fertilized egg. A pedigree for this family would resemble the inheritance pattern of an X-linked disorder with the likelihood of variable expression. 

Once the inheritance pattern of the disorder is determined, the status of family members in the pedigree can be evaluated. By carefully observing the position of affected individuals, mutation carriers may be identified. From this data, the risk of carrier status for other family members or the chance that a couple may have an affected child can be estimated. 

The answer is a. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 97-158. Wilson, pp 23-39.) Autosomal recessive conditions tend to have a horizontal pattern in the pedigree. Men and women are affected with equal frequency and severity. It is the pattern of inheritance most often seen in cases of deficient enzyme activity (inborn errors of metabolism). Autosomal recessive conditions tend to be more severe than dominant conditions and are less variable than dominant phenotypes. Both alleles are defective but do not necessarily contain the exact same mutation. All individuals carry 6 to 12 mutant recessive alleles. Fortunately, most matings involve persons who have mutations at different loci. Since related persons are more likely to inherit the same mutant gene, consanguinity increases the possibility of homozygous affected offspring. 

The answer is c. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 97-158. Wilson, pp 23-39.) In an autosomal dominant pedigree, there is a vertical pattern of inheritance. Assuming the disorder is not the result of a new mutation, every affected person has an allected parent. The same is true of X-linked dominant pedigrees. However, male-to-male transmission, as seen in this family, excludes the possibility ol an X-linked disorder. A person with an autosomal dominant phenotype has one mutant allele and one normal allele. These people randomly pass one or the other of these alleles to their offspring, giving a child a 50% chance of inheriting the... 

Polycystic kidney disease is a signiiicant cause of renal failure that presents from early infancy to adulthood. Early-onset cases tend to affect one family member or siblings, while adult-onset cases often show a vertical pattern in the pedigree. Which of the following offers the best explanation of these facts ... 

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