here are other examples of imprinting important to obstetrics. Complete hydatidiform mole, with a paternally derived diploid chromosomal complement, is characterized by abundant
TABLE 13-5. Some Disorders That Can Involve Imprinting
Angelman lSq11.2-q13 Maternal
Beckwith-Wiedemann 11 p1S.5 Paternal
Prader-Willi lSq11l.2-q13 Paternal
Pseudohypoparathyroidism 20q13.2 Variable
Russell-Silver syndrome 7p1l1.2 Maternal
Data from Online Mendelian Inheritance in Man (Johns Hopkins University, 201l7.) placental growth with no fetal structures (Chap. 20, p. 389). Conversely, an ovarian teratoma, with a maternally derived diploid chromosomal complement, is characterized by the growth of various fetal but no placental tissues (Porter, 1993).
his occurs when both members of a chromosome pair are inherited from the same parent. Often, uniparental disomy does not have clinical consequences. Although both copies are inherited from one parent, they are not identical. However, if chromosomes 6, 7, 11, 14, or 15 are involved, ofspring are at increased risk for an abnormality because of parent-of-origin diferences in gene expression (Shafer, 2001). Several genetic mechanisms may cause uniparental disomy, the most common of which is trisomic rescue, shown in Figure 13-9. After a nondisjunction event produces a trisomic conceptus, one of the three homologues may be lost. his will result in uniparental disomy for that chromosome in approximately one third of cases.
Isodisomy is the unique situation in which an individual receives two identical copies of one chromosome in a pair from one parent. his mechanism explains some cases of cystic ibrosis, in which only one parent is a carrier but the fetus inherits two copies of the same abnormal chromosome from that parent (Spence, 1988; Spotila, 1992). It also has been implicated in abnormal growth related to placental mosaicism.
Traits or diseases are considered to have multifactorial inheritance if they are determined by the combination of multiple genes and environmental factors (Table 13-6). Polygenic traits are determined by the combined efects of more than one gene. Most congenital and acquired conditions, as well as common traits, display multifactorial inheritance. Examples include malformations such as clefts and neural-tube defects, diseases such as diabetes and heart disease, and features or traits such as head
TABLE 13-6. Characteristics of Multifactorial Diseases
There is a genetic contribution:
No mendelian pattern of inheritance
No evidence of single-gene disorder
Nongenetic factors are also involved in disease causation: Lack of penetrance despite predisposing genotype Monozygotic twins may be discordant
Familial aggregation may be present:
Relatives are more likely to have disease-predisposing alleles
Expression more common among close relatives:
Adapted from Nussbaum, 2007. Genetics 269
FIGURE 13-9 Mechanism of uniparental disomy arising from trisomic "rescue." A. In normal meiosis, one member of each pair of homologous chromosomes is inherited from each parent. B. If nondisjunction results in a trisomic conceptus, one homologue is sometimes lost. In a third of cases, loss of one homologue leads to uniparental disomy.
size or height. Abnormalities that display multifactorial inheritance tend to recur in families, but not according to a mendelian pattern. If a couple has had a child with a multifactorial birth defect, their empirical risk to have another afected child is 3 to 5 percent. This risk declines exponentially with successively more distant relationships.