By ANDREW BRIDGES, AP Science Writer

LOS ANGELES (AP) - Researchers working with clones of a Holstein cow say genetic programming errors may explain why so many cloned animals of all types die, either as fetuses or newborns.

In cloning, the DNA of an adult animal is inserted into a donor egg emptied of its own DNA. For that cell to develop, genes that may have been turned off in the adult animal that was being cloned must be turned on again to guide the egg to form a new, genetically identical individual.

In females, the embryo receives two X chromosomes, each containing several hundred genes. In natural reproduction, the genes on the two X's are active in female embryos; one of the X's is later inactivated to match the male complement of one X and one Y chromosome.

However, female clones receive an active X and an already inactive X; the latter, and all its genes, must be reprogrammed and then, later in development, inactivated again.

Scientists at the University of Connecticut studying how the normal patterns of X chromosome inactivation are erased and then re-established during cloning found abnormalities in nine of 10 genes they examined on the X chromosome.

The scientists found the genes had been incompletely reprogrammed in five dead cow clones and one aborted fetus. Looking at four live clones, as well as control animals conceived naturally, the scientists found the same genes were normal.

"Our study demonstrates that in clones, even though they can develop to full term, many abnormalities in gene expression exist, which may be partially responsible for the developmental abnormalities frequently observed, including death," said Xiangzhong "Jerry" Yang, lead author of the study. Results appear online Sunday in the journal Nature Genetics.

Dr. Robert Lanza, medical director of Advanced Cell Technology and an expert in the cloning of cows, called the study "solid" and said that it helps explain the high death rate in cloning. More than 80 percent of clones die during pregnancy or shortly after birth.

"This work gives us a handle on what the problems might be so we can screen for them at the various steps," Lanza said.

Cloning is being eyed for dairy and beef cattle to reproduce the genetic traits that make those animals commercially valuable.

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Nature Genetics: http://www.nature.com/ng/

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