染色体畸变(一)结构改变解析.ppt

From a genetic standpoint, perhaps the most interesting aspect of fragile X syndrome is the instability of the CGG repeats. An individual with 6-54 repeats transmits a gene containing the same number to his or her offspring. However, those with 55-200 repeats, while not at risk to develop the syndrome, may transmit to their offspring a gene with an increased number of repeats. The number of repeats continues to increase in future generations, demonstrating the phenomenon known as genetic anticipation, first introduced in Chapter 4. Once the threshold of 200 is exceeded, expression of the malady becomes more severe in each successive generation as the number of trinucleotide repeats increases. While the mechanism that leads to the trinucleotide expansion has not yet been established, several factors are known that influence the instability. Most significant is the observation that expansion from the carrier status (55-200 repeats) to the syndrome status (over 200 repeats) occurs during the transmission of the gene by the maternal parent, but not by the paternal parent. Furthermore, several reports suggest that male offspring are more likely to receive the increased repeat size leading to the syndrome than are female offspring. Obviously, we have much to learn about the genetic basis of instability and expansion of DNA sequences A second link between a fragile site and a human disorder was reported in 1996 by Carlo Croce, Kay Huebner, and their colleagues, who demonstrated an association between an autosomal fragile site and cancer. They showed that the gene FHIT (standing for fragile histidine triad), located within a well-defined fragile site on chromosome 3, is often altered in cells taken from tumors of individuals with lung cancer. A variety of mutations were found in cells derived from the tumors where the DNA had apparently been broken and incorrectly refused, resulting in deletions within the gene. In most cases, these mutations caused the FHIT gene to bec