New evidence supports genomic imprinting.

New evidence supports genomic imprinting 

In a mid-19th-century monastery garden, Gregor Mendel's experiments with smooth and wrinkled peas revealed the rules by which parents pass on traits to their offspring. But a theory called genomic imprinting is putting a new wrinkle into Mendelian genetics: A gene's expression may depend on which parent contributed in (SN: 5/20/89, p.312).

In the latest finding, Susan Malcolm of the Institute of Child Health in London and her colleagues report in the March 23 LANCET on two children who developed a rare type of mental retardation called Angelman's syndrome. Because of an error during sperm formation, each child inherited two chromosome 15 segments from the father and none from the mother, a rare condition called uniparental paternal disomy. According to Mendelian genetics, neither child should have suffered ill effects because each got a normal and complete set of genetic material, albeit from only one parent.

The British report parallels a finding by Robert D. Nicholls and other researchers at the Children's Hospital in Boston that a double dose of maternal chromosome 15 leads to a clinically different form of mental retardation called Pradel-Willi syndrome (SN: 11/18/89, p.324).

The results of these two studies strongly support genomic imprinting in humans, Malcolm says, because they show that the same gene has different effects depending on its parental origin.

"Clearly, for this bit of chromosome 15 [to function properly], you just have to have a contribution from mother and a contribution from father--which Mendel didn't know about," Malcolm told SCIENCE NEWS.

Researchers suspected the influence of genomic imprinting in the two syndromes because each had an odd inheritance pattern. Using DNA probing techniques developed in this 1980's, geneticists had discovered that about half of Angelman's cases were missing genetic material from a portion of the mother's chromosome 15 and about 60 percent of Pradel-Willi cases were missing material from the father's chromosome 15. In the rest of the individuals with these syndromes, however, researchers couldn't find chromosomal deletions; this led them to suspect uniparental disomy. The 1989 discovery of a double dose of maternal chromosome 15 in six cases of Prader-Willi syndrome stimulated researchers to search for double paternal chromosomes in Angelman's patients, says Judith G. Hall of University Hospital in Vancouver, British Columbia.

The findings have profound implications for genetics researchers and genetic counselors, Hall says. Researchers should look at other disorders involving chromosomal deletions for further evidence of genomic imprinting effects, she told SCIENCE NEWS.

Scientists don't know how much of the human genome is under the influence of genetic imprinting, says Nicholls, now at the University of Florida College of Medicine at Gainesville. Nor do they know exactly how imprinting operates, or even why it evolved. Ever since the first observation in 1984 of differences in maternal and paternal gene expression in mice, scientists have sought to discover the chemical process by which some genes are imprinted, or silenced.

Regardless of how or why imprinting takes place, these recent discoveries could affect the reproductive decisions of couples with an Angelman's or Prader-Willi child. To properly advise these couples, Malcolm says, genetic counselors must know which genetic mistake caused the syndrome. If a child is mentally retarded because of a uniparental disomy, then neither parent has a defective chromosome. Because uniparental disomy is rare, Malcolm says, these parents can be assured that the syndromes "would be unlikely to recur."