Chapter 11 - Pedigrees

Human pedigrees

• Patterns for over 2,500 inherited human characteristics have so far been determined.
• Humans cannot be studied using planned crosses, so human geneticists rely on pedigrees, which show phenotype segregation in several generations of related individuals.
• Since humans have such small numbers of offspring, human pedigrees do not show clear proportions.
• The actual number of affected versus unaffected offspring is impossible to predict for a certain couple because outcomes for small samples fail to follow closely the expected outcomes.
• If neither parent has a given phenotype, but it shows up in progeny, the trait is recessive and the parents are heterozygous. The chance of other children getting the trait is 1/4.
• Half of the children from such a cross will be carriers (heterozygous for the trait).
• The probability of a carrier (heterozygote) for a rare allele unknowingly marrying another unrelated carrier is quite low.
• Marriage between close relatives results in a higher likelihood that both parents will be carriers of a rare allele and produce affected children.
• The major use of pedigree analysis is in clinical evaluation and counseling of patients with inherited abnormalities.

Pedigree for the Albino Trait

Pedigree for a Sex Linked Trait

The Story of Hemophilia

Late in the summer of 1818, a human sperm and egg united to form a human zygote. One of those gametes, we don't know which, was carrying a newly mutated gene. A single point mutation in a nucleotide sequence coding for a particular amino acid in a protein essential for blood clotting. The zygote became Queen Victoria of England and the new mutation was for hemophilia, bleeder's disease, carried on the X chromosome.

A century later, after passing through three generations, that mutation may have contributed to the overthrow of the Tsar and the emergence of communism in Russia. Victoria passed the gene on to some of her children and grandchildren, including Princess Alexandra, who married Nicholas II, Tsar of Russia, in 1894. By 1903, the couple had produced four daughters. The next year, the long awaited male heir appeared - His Imperial Highness Alexis Nicolaievich, Sovereign Heir Tsarevich, Grand Duke of Russia. From his father, the baby Alexis inherited the undisputed claim to the throne of all the Russias. From his mother, he inherited an X chromosome carrying a copy of the mutant gene for hemophilia. Soon after his birth, signs of Alexis' mutant gene appeared. At six weeks, he experienced a bout of uncontrolled bleeding and by early 1905 the royal physicians had concluded that he was suffering from hemophilia.

Contrary to popular belief, inbreeding does not result in "monstrous" offspring. Marrying close relatives, as often occurred in royal families did increase the chances that recessive harmful alleles (like hemophilia) would be inherited.

Inbreeding has caused many breeds of dogs to have harmful genetic traits. Dalmations are often deaf, and other dog breeds have high frequencies of epilepsy, blindness, and hip displaysia. It is true, that mutts are often hardier and have less health problems.