Lesson 9 — Pedigree Analysis


Patterns of Inheritance

Three patterns of inheritance are studied in this lesson: autosomal dominant, autosomal recessive, and sex-linked recessive.

Autosomal Dominant

Remember that autosomal chromosomes are all chromosomes that are not sex chromosomes. In other words, anything that is not an X or a Y chromosome is an autosome. A dominant trait usually shows in a pedigree by having an affected individual in every generation.

Notice how all affected offspring have affected parents in the above pedigree.  Unaffected individuals of an autosomal dominant trait must be homozygous recessive so two unaffected parents cannot have affected offspring.  Because a single copy of the affected gene is sufficient to express the trait, offspring might not inherit the dominant allele. When this gene is not inherited, the trait ceases to exist in subsequent generations from the unaffected individuals. No carriers occur for the trait because both heterozygous and homozygous dominant individuals express the trait. In addition, an autosomal trait does not show any preference to sex, providing approximately the same number of affected males as females.

From the above pedigree, we can deduce that the affected male in the first generation is a heterozygous individual because three of his children were not affected. The mother is unaffected; therefore, she can pass only the recessive alleles to her six children. The father must have contributed an unaffected, recessive allele to three of his children and affected, dominant alleles to the remaining three children. This means that three affected individuals in the second generation are also heterozygous for the trait. Furthermore, the affected individual in the third generation is also heterozygous because their mother only carries the recessive alleles. All unaffected individuals are homozygous recessive.

Autosomal Recessive
An autosomal recessive trait shows in pedigrees when neither parent expresses the trait. If the pedigree is long enough, it may indicate the disease showing a few generations later. Similar to autosomal dominant traits, male and female offspring should be equally represented in the affected individuals for autosomal recessive inheritance.

Because both parents of the affected individuals in the pedigree above are unaffected, we can assume that they are both heterozygous carriers of the trait. However, a marriage between cousins resulted in homozygous recessive offspring for the rare allele.  Affected individuals of an autosomal recessive trait must be homozygous recessive, so two affected parents cannot have unaffected offspring. 

In the above pedigree, both affected individuals are homozygous recessive (aa), and their parents are heterozygous dominant (Aa). The second and third children in the second generation must be heterozygous dominant (Aa) to pass the affected allele to their children. All remaining phenotypically normal individuals have at least one copy of the dominant allele (A_). We cannot be certain of their genotype due to a small sampling of the pedigree. When whether an individual is homozygous dominant (AA) or heterozygous dominant (Aa) cannot be determined, this is indicated with a blank line as in A_.

Sex-Linked Recessive
When the trait being studied is found on an X or a Y chromosome, the inheritance pattern is said to be sex-linked. Sex-linked inheritance has some distinguishing features. The first is a sex bias. For X-linked recessive traits, males are affected more commonly than females are. This is because a female expresses the recessive trait only if both her mother and father pass the trait, as shown in the pedigree above. The single affected female in the fourth generation resulted from an affected father and a mother who is a carrier of the red-green blindness.

Remember that males give their X chromosomes to their daughters and not to their sons. Therefore, in an X-linked recessive pedigree, often an affected male appears to have no affected offspring as shown in the first and second generation. In such a case, one or more of his daughters will be carriers and will have sons affected with the disease.

Summary

Pattern of Inheritance
 Characteristic  Examples
 Autosomal Dominant
  • generally will show in every generation
  • affected individuals generally will have affected parents
  • if both parents are unaffected they cannot have affected offspring
 Huntington disease
 Autosomal Recessive
  • generally will skip generations
  • affected individuals may have unaffected parents
  • if both parents are affected they cannot have unaffected offspring
   albinism
  X-linked recessive
  •  in humans, more males are affected than females
  red-green blindness