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.
