Unseen Inheritance

ACCESSION NO:  90-91-0197
       TITLE:  Unseen Inheritance
      AUTHOR:  WEISS, RICK
     JOURNAL:  Science News
    CITATION:  July 7, 1990, 131: 8-11.
        YEAR:  1990
    PUB TYPE:  Article
 IDENTIFIERS:  HUMAN GENETICS; GENETIC IMPRINTING; CHROMOSOME ABNORMALITIES; 
               INHERITED DISORDERS; PRENATAL TESTING; UNIPARENTAL DISOMY

ABSTRACT: Human uniparental disomy is a bizarre genetic phenomenon which gives a child double doses of some genes from one parent and no equivalent genes from the other. The first documented case of this phenomenon was reported in 1988 by a molecular biologist who was looking for the gene that caused cystic fibrosis. Researchers say that the phenomenon may not be so rare; rather, the majority of embryos harboring the abnormality probably don't survive to term. Those that do may show only subtle abnormalities such as short stature or mild learning disabilities. Identifying and studying these people could yield a number of benefits, according to researchers. For example, it might shed light on genetic imprinting, in which identical genes behave differently depending on the gender of the contributing parent.

In the past decade, geneticists have theorized that some children might inherit an uneven distribution of chromosomes, getting a greater proportion from one than from the other. Some of the first hints came from tissue analyses of spontaneously aborted fetuses; they revealed a surprising number of trisomies (cells containing double contributions from one parent and a normal complement of chromosomes from the other) and x-chromosome monosomies (cells containing one, rather than two, sex chromosomes). Trisomies are not unknown in adult humans, but they are unusual. Down's syndrome, for example, appears in people who inherit three copies of chromosome 21 instead of the usual two. Further, a growing body of evidence has geneticists suspecting that uniparental disomy may underlie a whole range of inherited disorders.

Since documentation of the case of uniparental disomy, Israeli researchers also have attributed a case of cystic fibrosis to the phenomenon. A team of specialists at Children's Hospital in Boston identified six cases of Prader- Willi syndrome (a condition characterized by obesity, low IQ, and a lack of muscle tone) attributable to uniparental disomy. And French researchers have found a boy with hemophilia A, whose disease is likewise attributed to the genetic disorder.

Among other unexplained, inherited abnormalities that might be due to uniparental disomy are Beckwith-Wiedemann syndrome, Miller-Dieker syndrome, and Silver-Russel syndrome. Each involves variations of growth retardation and congenital anomalies. But in order to tie these or other syndromes to uniparental disomy, investigators need to perform detailed analyses of the DNA base sequence on all 23 pairs of human chromosomes, studying both the person in question and his or her parents. Although the number of DNA probes grows every month, the current selection still leaves large chromosomal regions essentially unmappable. Ultimately, however, as more and more human chromosomes are investigated by genetic probes, prenatal testing may routinely include searches for uniparental disomies.