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UGA researchers propose model for disorders caused by improper transmission of chromosomes
August 17, 2009Parents of healthy newborns often remark on the miracle of life. The joining of egg and sperm to create such delightful creatures can seem dazzlingly beautiful if the chromosome information from each parent has been translated properly into the embryo and newborn.
The darker side is that when extra copies of chromosomes or fewer than the normal 46 (23 from each parent) are present, tragic birth defects can occur. Now, scientists at the University of Georgia have developed a model system for plants and animals that shows the loss of a key structural protein can lead to the premature separation of one DNA copy called a chromatid.
The new model shows for the first time that the loss of this protein can lead to aneuploidy-the name given to birth disorders caused by extra or too few chromosomes. Disorders caused by errors in the proper transmission of chromosomes from each parent are uncommon but tragic nonetheless. Best known may be Down Syndrome, which is caused by an extra copy of chromosome 21. Many errors in chromosome transmission are so severe that miscarriages usually occur.
"As we know, human females have all the eggs they will ever have from the time of birth, and so as they age, the protein structures on chromosomes also age," said Kelly Dawe, a geneticist and plant biologist at UGA. "If an egg is fertilized late in life, the final stages of chromosome separation may not occur properly. The goal of the work, which was done in maize, is to find out which parts of the chromosomes are most sensitive to failure. We now believe that proteins in a structure called the kinetochore are among the most sensitive to degradation or mutation. That may be a clue as to why older women have more problems with these kinds of chromosomal disorders when giving birth than younger women."
The research was published today in the journal Nature Cell Biology. Co-author on the paper is former University of Georgia graduate student Xuexian Li.
Irregularities in chromosome number are usually caused during a biological event called meiosis, in which the number of chromosomes per cell is halved and, in animals, results in the formation of gametes or sex cells. While the biology of meiosis has been known for more than a century, major questions remain about how all the constituent cell parts must coordinate to make the process successful.
During the two stages of meiosis, chromosomes are first separated by type, ensuring that only one of each gene is represented and then separated in half again in preparation for fertilization. The authors showed that the first stage is orchestrated in part by the kinetochore that attaches chromosomes to the rest of the cell. When they suppressed a kinetochore protein called MIS12, the chromosomes no longer separated by type and jumped to the second stage before completing the first. These failures closely mimic those seen in eggs from older women.
The cell division processes that Dawe and Li studied have implications for other diseases-such as cancer-as well. And yet a genuine payoff may come in the form of genetically improved lines of corn.
Dawe's work opens the possibility of a more positive outcome: the ability to engineer so-called "artificial chromosomes" with useful genes into corn varieties. Though that may be years off, it could offer a way to create lines that could resist drought, disease and insect pests without harming the environment.
Researchers are racing to design artificial chromosomes that behave like natural ones. With such an engineered chromosome, the positives traits researchers could give to corn plants would be almost limitless.
"You could really put genes in there at will, stacking traits that would make the plants able to withstand problems that now limit production greatly all over the world," said Dawe. "But to get from theory to practice, we will need a much clearer understanding of meiosis."
Unfortunately, most early generation artificial chromosomes have failed at meiosis in a nearly identical manner as plants with reduced MIS12. By manipulating MIS12 or other similar proteins, Dawe hopes to correct these defects.
University of Georgia
"As we know, human females have all the eggs they will ever have from the time of birth, and so as they age, the protein structures on chromosomes also age," said Kelly Dawe, a geneticist and plant biologist at UGA. "If an egg is fertilized late in life, the final stages of chromosome separation may not occur properly. The goal of the work, which was done in maize, is to find out which parts of the chromosomes are most sensitive to failure. We now believe that proteins in a structure called the kinetochore are among the most sensitive to degradation or mutation. That may be a clue as to why older women have more problems with these kinds of chromosomal disorders when giving birth than younger women."
The research was published today in the journal Nature Cell Biology. Co-author on the paper is former University of Georgia graduate student Xuexian Li.
Irregularities in chromosome number are usually caused during a biological event called meiosis, in which the number of chromosomes per cell is halved and, in animals, results in the formation of gametes or sex cells. While the biology of meiosis has been known for more than a century, major questions remain about how all the constituent cell parts must coordinate to make the process successful.
During the two stages of meiosis, chromosomes are first separated by type, ensuring that only one of each gene is represented and then separated in half again in preparation for fertilization. The authors showed that the first stage is orchestrated in part by the kinetochore that attaches chromosomes to the rest of the cell. When they suppressed a kinetochore protein called MIS12, the chromosomes no longer separated by type and jumped to the second stage before completing the first. These failures closely mimic those seen in eggs from older women.
The cell division processes that Dawe and Li studied have implications for other diseases-such as cancer-as well. And yet a genuine payoff may come in the form of genetically improved lines of corn.
Dawe's work opens the possibility of a more positive outcome: the ability to engineer so-called "artificial chromosomes" with useful genes into corn varieties. Though that may be years off, it could offer a way to create lines that could resist drought, disease and insect pests without harming the environment.
Researchers are racing to design artificial chromosomes that behave like natural ones. With such an engineered chromosome, the positives traits researchers could give to corn plants would be almost limitless.
"You could really put genes in there at will, stacking traits that would make the plants able to withstand problems that now limit production greatly all over the world," said Dawe. "But to get from theory to practice, we will need a much clearer understanding of meiosis."
Unfortunately, most early generation artificial chromosomes have failed at meiosis in a nearly identical manner as plants with reduced MIS12. By manipulating MIS12 or other similar proteins, Dawe hopes to correct these defects.
University of Georgia
Chromosomes Current Events and Chromosomes News RSSScientists at UA, collaborating institutions decode maize genome
Scientists from the University of Arizona led by Arizona Genomics Institute director Rod A. Wing and from collaborating institutions have deciphered the complete genetic code of the maize plant for the first time.
New map of variation in maize genetics holds promise for developing new varieties
A new study of maize has identified thousands of diverse genes in genetically inaccessible portions of the genome. New techniques may allow breeders and researchers to use this genetic variation to identify desirable traits and create new varieties that were not easily possible before.
New Maize Map to Aid Plant Breeding Efforts
In a massive survey of genetic diversity in maize, also known as corn, researchers across the United States, have developed a gene map that should pave the way to significant improvements in a plant that is a major source of food, fuel, animal feed and fiber around the world.
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Largest gene study of childhood IBD identifies 5 new genes
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Researchers funded in part by the National Institutes of Health have discovered how to transform human embryonic stem cells into germ cells, the embryonic cells that ultimately give rise to sperm and eggs.
A solution to Darwin's 'mystery of the mysteries' emerges from the dark matter of the genome
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Common weed could provide clues on aging and cancer
A common weed and human cancer cells could provide some very uncommon details about DNA structure and its relationship with telomeres and how they affect cellular aging and cancer, according to a team led by scientists from Texas A&M University and the University of Cincinnati (UC).
CSHL-led team discovers rare mutation dramatically increasing schizophrenia risk
An international team of researchers led by geneticist Jonathan Sebat, Ph.D., of Cold Spring Harbor Laboratory (CSHL), has identified a mutation on human chromosome 16 that substantially increases risk for schizophrenia.
Standards for a new genomic era
A team of geneticists at Los Alamos National Laboratory, together with a consortium of international researchers, has recently proposed a set of standards designed to elucidate the quality of publicly available genetic sequencing information.
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