 |
|
Research sheds light on cause of Down syndrome and other genetic disorders
July 20, 2009Scientists have a better understanding of what causes an abnormal number of chromosomes in offspring, a condition called aneuploidy that encompasses the most common genetic disorders in humans, such as Down syndrome, and is a leading cause of pregnancy loss.
To pinpoint what goes awry in these cases, researchers at the U.S. Department of Energy's Lawrence Berkeley National Laboratory and the University of Tennessee, Knoxville studied mice. They found that if a mother's egg cell has a mutation in just one copy of a gene, called Bub1, then she is more likely to have fewer offspring that survive to birth.
Ordinarily, both copies of a gene in a chromosome must carry the same mutation in order for an organism to be adversely effected.
"But we found that a mutation in a single copy of the Bub1 gene can have an impact - and this is not the case with most genes. With Bub1, if you have one bad gene and one healthy gene, there's a problem," says Francesco Marchetti of Berkeley Lab's Life Sciences Division. He worked with Sundaresan Venkatachalam of the University of Tennessee and other scientists on the research. Their findings appear in the online early edition of the Proceedings of the National Academy of Sciences the week of July 13.
The importance of their discovery is underscored by the fact that it's rare for humans to have mutations in both copies of a gene, while it is quite common to have a mutation in only one copy. Usually, the healthy gene overrides the mutated gene -- but not in Bub1, at least in mice.
"This means that having only one mutated Bub1 gene could be a significant predisposing factor for passing on an abnormal number of chromosomes to offspring," says Marchetti.
The scientists also found that the harmful effects of this mutation increased with a mother's age. The older the female mice got, the fewer offspring they had. The same is true in humans: the chance of having an aneuploid pregnancy increases with the age of the mother. In addition, the scientists found that the same mutation in sperm cells had no effect on the health of offspring.
The research sheds light on the genetic underpinnings of aneuploidy, a condition marked by having an abnormal number of chromosomes. It is the underlying cause of many genetic diseases - such as Down syndrome, Edwards syndrome, and Patau syndrome - as well as many cases of pregnancy loss.
For the past several years, scientists have used mice to study the genetic causes of aneuploidy. They've zeroed in on mutations in a handful of genes as the culprits, including Bub1. The gene plays a role in a cell's spindle assembly checkpoint, which is a control mechanism that ensures that chromosomes are properly divided during meiosis, the cell division process that enables a stem cell to become an egg. This checkpoint hiccups when Bub1 is mutated, sometimes producing an egg with an extra chromosome and sometimes producing an egg with a missing chromosome.
Bub1 is also a favorite target of scientists studying cancer development, which is why Venkatachalam initially developed mice that were heterozygous for the gene, meaning they had one normal and one mutated copy. As so often happens in science, however, he serendipitously noticed that these mice had fewer babies. Intrigued, he enlisted the help of Marchetti and Berkeley Lab postdoc Aris Polyzos of the Life Sciences Division to help understand why.
The team found that when a male with one bad copy of the gene mated with a normal female, their number of offspring was normal. But when a female with a bad copy of the gene mated with a normal male, very few babies were born. Further research revealed this is because aneuploidy was generated in the egg and passed on to the single-cell zygote that forms when a sperm fertilizes an egg. And this led to the loss of the embryo.
"We found that in female mice a single copy of an abnormal Bub1 gene is sufficient to produce aneuploidy, and this risk increases with age," says Marchetti. "Our work may help explain how aneuploidy occurs in humans, and why the risk for the condition increases with a mother's age."
"Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice" is published in the July 13-17, 2009 online early edition of the Proceedings of the National Academy of Sciences. This research was performed in part under the auspices of the U.S. Department of Energy.
Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California for the DOE Office of Science. Visit our website at http://www.lbl.gov
Lawrence Berkeley National Laboratory
"But we found that a mutation in a single copy of the Bub1 gene can have an impact - and this is not the case with most genes. With Bub1, if you have one bad gene and one healthy gene, there's a problem," says Francesco Marchetti of Berkeley Lab's Life Sciences Division. He worked with Sundaresan Venkatachalam of the University of Tennessee and other scientists on the research. Their findings appear in the online early edition of the Proceedings of the National Academy of Sciences the week of July 13.
The importance of their discovery is underscored by the fact that it's rare for humans to have mutations in both copies of a gene, while it is quite common to have a mutation in only one copy. Usually, the healthy gene overrides the mutated gene -- but not in Bub1, at least in mice.
"This means that having only one mutated Bub1 gene could be a significant predisposing factor for passing on an abnormal number of chromosomes to offspring," says Marchetti.
The scientists also found that the harmful effects of this mutation increased with a mother's age. The older the female mice got, the fewer offspring they had. The same is true in humans: the chance of having an aneuploid pregnancy increases with the age of the mother. In addition, the scientists found that the same mutation in sperm cells had no effect on the health of offspring.
The research sheds light on the genetic underpinnings of aneuploidy, a condition marked by having an abnormal number of chromosomes. It is the underlying cause of many genetic diseases - such as Down syndrome, Edwards syndrome, and Patau syndrome - as well as many cases of pregnancy loss.
For the past several years, scientists have used mice to study the genetic causes of aneuploidy. They've zeroed in on mutations in a handful of genes as the culprits, including Bub1. The gene plays a role in a cell's spindle assembly checkpoint, which is a control mechanism that ensures that chromosomes are properly divided during meiosis, the cell division process that enables a stem cell to become an egg. This checkpoint hiccups when Bub1 is mutated, sometimes producing an egg with an extra chromosome and sometimes producing an egg with a missing chromosome.
Bub1 is also a favorite target of scientists studying cancer development, which is why Venkatachalam initially developed mice that were heterozygous for the gene, meaning they had one normal and one mutated copy. As so often happens in science, however, he serendipitously noticed that these mice had fewer babies. Intrigued, he enlisted the help of Marchetti and Berkeley Lab postdoc Aris Polyzos of the Life Sciences Division to help understand why.
The team found that when a male with one bad copy of the gene mated with a normal female, their number of offspring was normal. But when a female with a bad copy of the gene mated with a normal male, very few babies were born. Further research revealed this is because aneuploidy was generated in the egg and passed on to the single-cell zygote that forms when a sperm fertilizes an egg. And this led to the loss of the embryo.
"We found that in female mice a single copy of an abnormal Bub1 gene is sufficient to produce aneuploidy, and this risk increases with age," says Marchetti. "Our work may help explain how aneuploidy occurs in humans, and why the risk for the condition increases with a mother's age."
"Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice" is published in the July 13-17, 2009 online early edition of the Proceedings of the National Academy of Sciences. This research was performed in part under the auspices of the U.S. Department of Energy.
Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California for the DOE Office of Science. Visit our website at http://www.lbl.gov
Lawrence Berkeley National Laboratory
Aneuploidy Current Events and Aneuploidy News RSSA solution to Darwin's 'mystery of the mysteries' emerges from the dark matter of the genome
Biological species are often defined on the basis of reproductive isolation. Ever since Darwin pointed out his difficulty in explaining why crosses between two species often yield sterile or inviable progeny (for instance, mules emerging from a cross between a horse and a donkey), biologists have struggled with this question.
Protein helps cells duplicate correctly, avoid becoming cancer
A Purdue University researcher has discovered that the absence of certain proteins needed for proper cell duplication can lead to cancer.
When you've doubled your genes, what's 1 chromosome more or less?
An individual with Down syndrome and a male calico cat have one thing in common-each has an extra chromosome. For animals, most instances of an extra chromosome result in birth defects or even death, but plants are another matter entirely.
UGA researchers propose model for disorders caused by improper transmission of chromosomes
Parents 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.
New research finds possible genetic link to cause of pregnancy loss and disorders
Scientists at the University of Tennessee, Knoxville, and Lawrence Berkeley National Laboratory (LBNL) have published new findings about a cause of a condition at the root of genetic disorders such as Down Syndrome, pregnancy loss and infertility.
Chromosomal problems affect nearly all human embryos
For the first time, scientists have shown that chromosomal abnormalities are present in more than 90% of IVF embryos, even those produced by young, fertile couples.
New test can detect both genetic and chromosomal abnormalities in embryos
One-step screening for both genetic and chromosomal abnormalities has come a stage closer as scientists announced that an embryo test they have been developing has successfully screened cells taken from spare embryos that were known to have cystic fibrosis.
New blood test for Down syndrome
Howard Hughes Medical Institute researchers have developed a new prenatal blood test that accurately detected Down syndrome and two other serious chromosomal defects in a small study of 18 pregnant women.
Bladder cancer detected via amplified gene in cells found in urine
Counting the copies of a specific gene in cells gathered from a urine sample may provide a simple, noninvasive way to detect bladder cancer, a team led by researchers at The University of Texas M. D. Anderson Cancer Center reports in the Journal of the National Cancer Institute.
Levels of folate in men's diets is linked to chromosomal abnormalities in their sperm
Researchers have found an association between a vitamin found in leafy green vegetables, fruit and pulses and levels of chromosomal abnormalities in men's sperm. Men who consumed high levels of folate (a water-soluble B vitamin that occurs naturally in food) and folic acid (the synthetic form of the vitamin) tended to have lower levels of abnormal sperm where a chromosome had been lost or gained (known as aneuploidy).
More Aneuploidy Current Events and Aneuploidy News Articles
 |
Oncogenes, Aneuploidy, and AIDS: A Scientific Life and Times of Peter H. Duesberg by Harvey Bialy (Author) The author is an unabashed friend of Peter Duesberg and makes no bones about it in this personalized account of some of what the transformation of classical molecular biology into biotechnology has wrought. Most people, even many molecular biologists, will either not know or remember that two of the great themes of modern medicine, AIDS and cancer genes, both directly derive from the pioneering work on retroviruses of Peter Duesberg and a handful of others in the 1970s. Thus Duesberg's more than two decade, ongoing theoretical and experimental critiques of the dominant etiological explanations in each of these fields comes from substantial scientific contributions over a highly distinguished professional career that not only placed him in the US National Academy of Sciences at the young... |
|
Aneuploidy (Progress and topics in cytogenetics) by Liss (Publisher) | |
|
Aneuploidy:Etiology and Mechanisms (Basic Life Sciences) (Vol 36) by Vicki Dellarco (Editor) | |
|
Aneuploidy (Oxford Monographs on Medical Genetics) by D. J. Bond (Author), A. C. Chandley (Author) | |
|
Sex chromosome aneuploidy: Prospective studies on children (Birth defects original article series) by A. R. Liss (Publisher) | |
|
Children with sex chromosome aneuploidy: Follow-up studies : proceedings of a conference held in Toronto, Ontario, Canada (Birth defects : original article series) by A.R. Liss (Publisher) | |
|
Tumor Aneuploidy by T. Buchner (Contributor) | |
|
Chromosome Segregation and Aneuploidy (Nato Asi Series H : Cell Biology, Vol 72) by Baldev K. Vig (Editor) Aneuploidy - the greatest genetic affliction of man - has its origin in many cellular processes. Its forerunner, chromosome non-disjunction, can result from malfunction of one of many processes involved in faithful segregation of chromosomes during mitosis or meiosis. Experts on chromosome biology, centromere, kinetochore, microtubules, spindle apparatus, biochemistry of mitosis and meiosis, developmental biology, and environmental mutagenesis discuss basic and applied aspects of how chromosomes malsegregate and how aneuplody originates. The most recent techniques employed to study chromosome segregation and also methods to determine aneugenic chemicals are described. | |
|
Children and Young Adults with Sex Chromosome Aneuploidy : Follow-up, Clinical, and Molecular Studies by Ont.) International Workshop on Sex Chromosome Anomalies 1989 (Minaki (Author), John L. Hamerton (Author), Jane A. Evans (Author), Arthur Robinson (Author), Arthur Robinson (Editor), March of Dimes Birth Defects Foundation (Editor) Reports from the fifth workshop for investigators carrying out prospective longitudinal studies on children and young adults with sex chromosome anomalies are presented. Part I updates the studies and provides an unbiased summary of the prognosis for a fetus or newborn diagnosed with a sex chromosome anomaly. Part II deals with clinical and therapeutic observations and provides the first critical attempt at evaluating various therapeutic modes which may be useful for patients with the 45,X and 47,XXY karyotypes. There is also critical information concerning patients with Turner and Klinefelter syndromes. The book, the result of more than 20 years of international effort, will be of value to professionals who treat patients with sex chromosome anomalies and their families as well as to... | |
 |
Aneuploidies: Webster's Facts and Phrases by Icon Group International (Author) Ever need a fact or quotation on "aneuploidies"? Designed for speechwriters, journalists, writers, researchers, students, professors, teachers, historians, academics, scrapbookers, trivia buffs and word lovers, this is the largest book ever created for this word. It represents a compilation of "single sentences" and/or "short paragraphs" from a variety of sources with a linguistic emphasis on anything relating to the term "aneuploidies," including non-conventional usage and alternative meanings which capture ambiguities. This is not an encyclopedic book, but rather a collage of statements made using the word "aneuploidies," or related words (e.g. inflections, synonyms or antonyms). This title is one of a series of books that considers all major vocabulary words. The entries in each book... |
| © 2009 BrightSurf.com |