Besides autosomal and sex-linked genes and mitochondrial inheritance, it was found that certain genes exhibit a “parent of origin” type of transmission in which the parental genomes do not always contribute equally in the development of a person (Fig. 6.10). The transmission of this phenomenon is called genetic imprinting. Although rare, it is estimated that approximately 100 genes exhibit genetic imprinting. Evidence suggests a genetic conflict occurs in the developing embryo: the male genome attempts to establish larger offspring, whereas the female prefers smaller off-spring to conserve her energy for the current and subsequent pregnancies.
It was the pathologic analysis of ovarian teratomas (tumors made up of various cell types derived from an undifferentiated germ cell) and hydatidiform moles (gestational tumors made up of trophoblastic tissue) that yielded the first evidence of genetic imprinting. All ovarian teratomas were found to have a 46, XX karyotype. The results of detailed chromosomal polymorphism analysis confirmed that these tumors developed without the paternally derived genome. Conversely, analysis of hydatidiform moles suggested that they were tumors of paternal origin.
Well-known examples of genomic imprinting are the transmission of the mutations in Prader-Willi and Angelman syndromes. Both syndromes exhibit mental retardation as a common feature. It was also found that both disorders had the same deletion in chromosome 15. When the deletion is inherited from the mother, the infant presents with Angelman (“happy puppet”) syndrome. When the same deletion is inherited from the father, Prader-Willi syndrome results.
A related chromosomal disorder is uniparental disomy. This occurs when two chromosomes of the same number are inherited from one parent. Normally, this is not a problem except in cases where a chromosome has been imprinted by a parent. If imprinting inactivates an allele, the offspring will have only one working copy of the chromosome, resulting in possible problems.