Abnormalities see Birth Defects Achondroplasia see Dwarfism Acid Maltase Deficiency see Metabolic Disorders Adrenoleukodystrophy see Leukodystrophies Alpha-1 Antitrypsin Deficiency Anencephaly see Neural Tube Defects Arnold-Chiari Malformation see Head and Brain Malformations Brain Malformations see Head and Brain Malformations Canavan Disease see Leukodystrophies Dandy-Walker Syndrome see Head and Brain Malformations Duchenne Muscular Dystrophy see Muscular Dystrophy Fragile X Syndrome see Genetic Disorders Human Genome Project see Genes Hypermobility Syndrome see Ehlers-Danlos Syndrome Mucopolysaccharidoses see Metabolic Disorders PKU see Phenylketonuria von Recklinghausen's Disease see Neurofibromatosis
Dec 20, 2009
Genetics and Birth Defects (Source:NIH)
Diseases and Genes
Introduction to Genes and Disease
Genes and Disease is a collection of articles that discuss genes and the diseases that they cause. These genetic disorders are organized by the parts of the body that they affect. As some diseases affect various body systems, they appear in more than one chapter.
With each genetic disorder, the underlying mutation(s) is discussed, along with clinical features and links to key websites. You can browse through the articles online, and you can also download a printable file (PDF) of each chapter.
From Genes and Disease you can delve into many online related resources with free and full access. For example, you can visit the human genome to see the location of the genes implicated in each disorder. You can also find related gene sequences in different organisms. And for the very latest information, you can search for complete research articles, and look in other books in the NCBI Bookshelf. Currently over 80 genetic disorders have been summarized, and the content of Genes and Disease is continually growing.
The sequence of the human genome is providing us with the first holistic view of our genetic heritage. While not yet complete, continued refinement of the data bring us ever closer to a complete human genome reference sequence. This will be a fundamental resource in future biomedical research.
The 46 human chromosomes (22 pairs of autosomal chromosomes and 2 sex chromosomes) between them house almost 3 billion base pairs of DNA that contains about 30,000 - 40,000 protein-coding genes. The coding regions make up less than 5% of the genome (the function of the remaining DNA is not clear) and some chromosomes have a higher density of genes than others.
Most of the genetic disorders featured on this web site are the direct result of a mutation in one gene. However, one of the most difficult problems ahead is to find out how genes contribute to diseases that have a complex pattern of inheritance, such as in the cases of diabetes, asthma, cancer and mental illness. In all these cases, no one gene has the yes/no power to say whether a person has a disease or not. It is likely that more than one mutation is required before the disease is manifest, and a number of genes may each make a subtle contribution to a person's susceptibility to a disease; genes may also affect how a person reacts to environmental factors. Unraveling these networks of events will undoubtedly be a challenge for some time to come, and will be amply assisted by the availability of the sequence of the human genome.
Introduction to Genes and Disease- Blood and Lymph Diseases
- Cancers
- The Digestive System
- Ear, Nose, and Throat
- Diseases of the Eye
- Female-Specific Diseases
- Glands and Hormones
- The Heart and Blood Vessels
- Diseases of the Immune System
- Male-Specific Diseases
- Muscle and Bone
- Neonatal Diseases
- The Nervous System
- Nutritional and Metabolic Diseases
- Respiratory Diseases
- Skin and Connective Tissue
- Chromosome Map
Dec 19, 2009
Scientists Crack Genetic Code of Two Common Cancers
It is being called a scientific breakthrough. British researchers say they have mapped the entire genetic code for two types of cancers -- small cell lung cancer and melanoma, the most deadly type of skin cancer.Discovery could revolutionize cancer care, saving millions of lives
All cancers are caused by changes in the DNA of cells. DNA carries the cells' genetic information. That information changes when cells gradually mutate from normal to abnormal and then to malignant over time.
Scientists say if they could only crack the genetic codes of different types of cancers, they could save millions of lives.
Blood tests could spot tumors early on. And treatment would be far more successful. Dr. Jeanny Aragon-Ching is an oncologist at the George Washington University Medical Center. She says this discovery is a step toward an era of personalized medicine. "That is the thrust now because, for instance, for different types of cancers, we have different types of drugs that target different domains or mutations," she said.
The more information doctors have about how cancer cells develop, the more precisely they can prescribe a treatment to target those particular cells.
British scientists found 30,000 mutations in melanoma, a type of skin cancer that accounts for 75 percent of skin cancer deaths. They also found 23,000 mutations in small cell lung cancer. But not all of these mutations cause cancer. "It is the role of physicians and scientists to find out which of those mutations are the driving force, or the driving mutation that actually led to the cancer," she said.
Eventually, scientists might be able to target pre-cancerous cells and prevent deadly tumors from forming. But that day is still far away. "As an oncologist, my goal would be to one day see that we can transform cancer into a chronic disease. Cure is probably too generous of a word the way I see it, but to convert it to something more like chronic disease that is treatable," she said.
Just like high blood pressure that can be controlled with medicine, cancer could be a disease without the suffering we associate with it. Medical scientists the world over are now working to catalogue all the genes that mutate in many types of cancer as part of an International Cancer Genome Consortium. In the United States they are studying cancers of the brain, ovaries and pancreas.
In addition to lung cancer and melanoma, scientists are examining the DNA of breast cancer, as well as cancers of the liver, the mouth and the stomach. "I think each step forward is a step toward our goal, our ultimate goal, which is to relieve the suffering from cancer," she said.
Dec 15, 2009
Scientists Discover New Species of Dinosaur
Paleontologists say the dinosaur they call Tawa, was about the size of a large dog, but with a longer tail.
Scientists have discovered the fossilized remains of a new meat-eating dinosaur in a quarry in New Mexico. They say the finding sheds light on the evolution of these extinct creatures.
Paleontologists say the dinosaur they call Tawa, named for the Hopi Native American sun god, was about the size of a large dog, but with a longer tail, stood about 70 centimeters tall at the hips and was two meters long. The two-legged creature also had razor-sharp teeth for eating meat.
Scientists conducting an analysis of the newly-discovered, 215 million year old fossils and other early dinosaur remains say Tawa also had the characteristics of two other dinosaurs - the giant, plant-eating sauropod and the horned Triceratops.
They believe Tawa is the common ancestor of both dinosaur groups that migrated from Argentina to other parts of the world during the Pangea period, between 200 and 300 million years ago, when geologists say the Earth's continents were compressed into a single landmass.
The fossil discovery suggests that Tawa also used a land bridge from South America to make its way to North America, when Tyrannosaurus Rex began evolving into modern day birds, according to Sterling Nesbitt, a researcher at the University of Texas who led a team of excavators.
"Tawa is a little bit of a surprise because it's preserving these very early traits that we see in dinosaurs while living with animals that are much more closely related to bird," said Nesbitt.
According to Nesbitt, Tawa might answer important questions about a dinosaur called Herrerasaurus, which was discovered in Argentina in the 1960s.
Herrerasaurus has traits like T. Rex - including sharp claws and teeth - but lacks other characteristics of the carnivore. Scientists hope to determine whether Herrerasaurus is a direct descendant of Tawa or part of a different species of dinosaurs.
Nesbitt say the Hayden Quarry in northern New Mexico, where the ancient fossils were unearthed, is a rich bed containing other prehistoric bones and artifacts. He says he plans to continue digging at the site to learn more about Tawa.
"We want to know how it grew, how the features changed as the animal got older," he said. "We also want to look at the anatomical details."
A description of the new dinosaur species is reported this week in the journal Science.
Dec 13, 2009
Gene action may lead to diabetes prevention, cure
| LOS ANGELES, Dec. 12 (Xinhua) -- A gene commonly studied by cancer researchers may provide answers to ways of fighting diabetes, a new study shows. The gene, known in the science world as PFKFB3, is a regulator for metabolism, which plays a vital role in the development of diabetes, according to the study appearing in the Dec. Journal of Biological Chemistry. The gene has been linked to the metabolic inflammation that leads to diabetes. Understanding how the gene works means scientists may be closer to finding ways to prevent or cure diabetes, said the study conducted by researchers at Texas AgriLife Research. "Because we understand the mechanism, or how the gene works, we believe a focus on nutrition will find the way to both prevent and reverse diabetes," said Dr. Chaodong Wu, AgriLife Research nutrition and food scientist who authored the paper with the University of Minnesota's Dr. Yuqing Hou. Wu said the research team will collaborate with nutritionists to identify what changes or supplements in a diet will activate the gene to prevent or stop the progression of diabetes. He believes nutritionists working with the biological chemists can help develop food consumption plans that either prevent people from developing metabolic inflammation or cause existing conditions to retreat. "First we will need to identify what effective compounds will trigger the gene to regulate metabolism," Wu said. "Then we need to determine what combinations within foods are more effective." Wu noted that while it is a major health concern in the U.S., obesity does not necessarily cause diabetes to develop; i.e., just because a person is overweight does not mean they have diabetes. Rather, "metabolic inflammation" causes or exacerbates the disease. Metabolic inflammation is different from classic inflammation because there is no infection, virus or bacteria present, though the symptoms appear similar. |
Nov 23, 2009
Gene Mutations Linked to Early-Onset Inflammatory Bowel Disease
An international team has discovered that mutations in either of 2 related genes cause a severe and rare form of inflammatory bowel disease in young children. The discovery allowed the researchers to successfully treat one of the study patients with a bone marrow transplant.
Inflammatory bowel disease is a group of disorders that includes Crohn's disease and ulcerative colitis. The inflammation, or swelling, of the intestines can cause pain, damage the tissue and make the intestines empty frequently, resulting in diarrhea. Previous studies have identified dozens of genes and variants that affect the risk for adult-onset inflammatory bowel disease, but none that singly cause the disease.
An international research team set out to search for genetic risk factors for early-onset inflammatory bowel disease. They examined DNA from 2 unrelated families with children who were affected by the disease. The research team, which was supported by several sources, included scientists from NIH's National Center for Biotechnology Information (NCBI), University College London in the United Kingdom, Hannover Medical School in Germany and several other institutions.
The scientists found that mutations in either of 2 genes are sufficient to cause early-onset inflammatory bowel disease, as reported in the advance online edition of the New England Journal of Medicine on November 4, 2009. Screening 6 additional patients with early-onset colitis identified another mutation in one of the genes. The 2 genes code for the proteins IL10R1 and IL10R2. These proteins act together to receive signals from interleukin 10, a signaling molecule that plays a crucial role keeping the body's inflammatory responses in check. When either IL10R1 or IL10R2 is mutated, the signals from IL10 cannot be received, and the resulting inflammation causes tissue damage, especially in the gastrointestinal system.
One of the young patients who hadn't responded to other therapies was given a bone marrow transplant from a healthy sibling. Bone marrow transplants can cure genetic disorders when the affected gene is normally active in marrow-derived cells. However, because of the risks associated with the procedure, the transplants are used only in cases of severe disease. This patient showed dramatic improvement following the procedure and has remained in remission from inflammatory bowel disease for more than a year.
"This is an excellent example of how discovery of causative genes and mutations can enable clinicians to go from bench to bedside for an informed treatment of patients," says Dr. Christoph Klein of Hannover Medical School, who led the diagnosis and treatment effort.
"This discovery is a milestone in research on inflammatory bowel disease, and will enable us to gain further insights into the physiology and immunity of the intestine," says Dr. Erik Glocker of University College London.
Nov 20, 2009
DNA Results Give New Hope for 'Extinct' Siamese Crocodiles
A proposed breeding program for the critically endangered Siamese crocodile received a significant boost this month with the news that 35 crocodiles at a wildlife rescue center in Cambodia are purebred Siamese.
Robert Carmichael | Phnom Penh 20 November 2009
A close-up of a Siamese crocodile hatchling at Phnom Tamao Wildlife Rescue Centre, Cambodia, 19 Nov 2009
A proposed breeding program for the critically endangered Siamese crocodile received a significant boost this month with the news that 35 crocodiles at a wildlife rescue center in Cambodia are purebred Siamese.
Siamese crocodiles have had a tough time. Twenty years ago they were declared extinct in the wild.
The crocodiles once ranged widely across Southeast Asia. But, coveted for their soft skin, Siamese crocodiles were poached to the very edge of existence.
However, in 2001 researchers discovered small populations of Siamese crocodiles in the wild in Cambodia. That meant the species went from being listed as extinct to critically endangered.
This month there was more good news. DNA tests on 69 crocodiles at a wildlife rescue center outside Phnom Penh found that 35 of them are purebred Siamese crocodiles.
Adam Scott, head of the crocodile project at Fauna and Flora International, holding a hatchling Siamese crocodile at Phnom Tamao Wildlife Rescue Centre
Adam Starr heads the crocodile conservation program at Fauna and Flora International, a conservation organization that works with the Cambodian government to protect Siamese crocodiles.
He says just 250 Siamese crocodiles exist in the wild in the world, most of them in Cambodia.
"How important is Cambodia? Very important. Siamese crocodiles used to exist throughout Southeast Asia. Indonesia, Malaysia, Thailand, Cambodia, Laos, Vietnam, everywhere. Now they are reduced from about 99 percent of their original population range area. We can say Cambodia hosts between 95 and 99 percent of the remaining wild crocodiles which is about 250," he said.
The tests proved invaluable in allowing researchers to distinguish between purebred Siamese crocodiles and hybrid crocodiles - something that can not be done just by looking at them.
Knowing which animals are hybrid is essential because conservationists do not want hybrids colonizing the country's rivers.
Nhek Ratanapech is the director of the Phnom Tamao Wildlife Rescue Center, where the purebred crocodiles live. He also heads the country's Crocodile Conservation Program.
He says the discovery of the purebreds could provide a critical lifeline for the preservation of Siamese crocodiles.
"Previously we have so many crocodiles but we didn't know which ones are pure Siamese crocodiles and which one is the hybrid one," he said. "Now we know exactly which one is pure and which is hybrid. We do hope that some potential donor help to support the activity to conserve or to stop this species being extinct from the world."
The problem of hybrids stems from crocodile farms, which bred Siamese crocodiles with other, faster-growing, larger, more aggressive crocodiles. The leather from the hybrid crocodile is still soft, and the hybrids provide more of it faster.
Nhek Ratanapech says the next step is to create a breeding program using the six mature purebreds at his center. The tests also showed that they are not related, which is vital for genetic diversity.
Their offspring will be kept for two years before being released into the wild, to maximize their chances of survival.
Nhek Ratanapech says the goal is to get Siamese crocodiles taken off the critically endangered list, which means reaching a target of 500 mature adults in the wild. As it takes 15 years for a Siamese crocodile to reach maturity, this is a long-term project.
But Cambodia is the Siamese crocodile's last chance. "So this population is on the verge of extinction and now Cambodia is the stronghold of this species," he said.
Adam Starr says many challenges remain. Human encroachment on the crocodile habitat is one problem; another is Cambodia's plans to build huge hydroelectric dams, which block rivers.
But those challenges are hardly new. And the DNA tests, which were carried out by a university in Thailand, have helped to move the project forward.
"What we're able to do now is work with a captive population that is of pure genetic stock and be able to start a breeding program and be able to reintroduce animals to areas where Siamese crocodiles once existed but have been eradicated due to poaching. So it's a very exciting phase we're about to embark upon," said Starr.
That sound is the call of a Siamese crocodile hatchling. It is a sound that Nhek Ratanapech and his colleagues hope will be heard across at least some of Cambodia's rivers in the coming years - as it was not long ago.
Jan 11, 2009
Is DNA effective in identifying persons?
[answer provided by Daniel Drell of the U.S. DOE Human Genome Program]
DNA identification can be quite effective if used intelligently. Portions of the DNA sequence that vary the most among humans must be used; also, portions must be large enough to overcome the fact that human mating is not absolutely random.
Consider the scenario of a crime scene investigation . . .
Assume that type O blood is found at the crime scene. Type O occurs in about 45% of Americans. If investigators type only for ABO, finding that the "suspect" in a crime is type O really doesn't reveal very much.
If, in addition to being type O, the suspect is a blond, and blond hair is found at the crime scene, you now have two bits of evidence to suggest who really did it. However, there are a lot of Type O blonds out there.
If you find that the crime scene has footprints from a pair of Nike Air Jordans (with a distinctive tread design) and the suspect, in addition to being type O and blond, is also wearing Air Jordans with the same tread design, you are much closer to linking the suspect with the crime scene.
In this way, by accumulating bits of linking evidence in a chain, where each bit by itself isn't very strong but the set of all of them together is very strong, you can argue that your suspect really is the right person.
With DNA, the same kind of thinking is used; you can look for matches (based on sequence or on numbers of small repeating units of DNA sequence) at many different locations on the person's genome; one or two (even three) aren't enough to be confident that the suspect is the right one, but thirteen sites are used. A match at all thirteen is rare enough that you (or a prosecutor or a jury) can be very confident ("beyond a reasonable doubt") that the right person is accused.
See some recent articles about statistical analysis on this topic:
NY Times Freakonomics Blog, Aug.19, 2008
Los Angeles Times, July 20, 2008
Jan 4, 2009
Double Helix: 50 Years of DNA
1953 was an annus mirabilis for science. Here, we present five classic papers from Nature that describe and provide evidence for the double helix being the structure of DNA, and one from The Journal of Experimental Medicine that has been described as the "defining moment in nucleic acid research".
A Structure for Deoxyribose Nucleic Acid
Watson J.D. and Crick F.H.C.
Nature 171, 737-738 (1953)
April 25, 1953: James Watson and Francis Crick's classic paper that first describes the double helical structure of DNA. With some understatement they note that the structure “suggests a possible copying mechanism for the genetic material”.
Molecular Structure of Deoxypentose Nucleic Acids
Wilkins M.H.F., A.R. Stokes A.R. & Wilson, H.R.
Nature 171, 738-740 (1953)
April 25, 1953: From the same issue, Wilkins, Stokes and Wilson analyse the X-Ray crystallography evidence, and suggest evidence that the structure exists in biological systems.
Molecular Configuration in Sodium Thymonucleate
Franklin R. and Gosling R.G.
Nature 171, 740-741 (1953)
April 25, 1953: Rosalind Franklin and Ray Gosling provide further evidence of the helical nature of nucleic acids, and conclude that the phosphate backbone lies on the outside of the structure.
Genetical Implications of the structure of Deoxyribonucleic Acid
Watson J.D. and Crick F.H.C.
Nature 171, 964-967 (1953)
May 30, 1953: Watson and Crick follow up with largely accurate speculation on how base pairing in the double helix allows replication of DNA.
Evidence for 2-Chain Helix in Crystalline Structure of Sodium Deoxyribonucleate
Franklin R. and Gosling R.G.
Nature 172, 156-157 (1953)
July 25, 1953:
Studies on the chemical nature of the substance inducing transformation of Pneumococcal types
Avery, O.T., MacLeod, C.M. & McCarty, M.
J. Exp. Med. 79, 137-159 (1944)
February 1, 1944: In this classic paper from the Journal of Experimental Medicine, Mac McCarty's team showed for the first time that DNA is the material of inheritance, the so-called stuff of life. Until then, biologists thought that 'genes', the units of inheritance, were made of protein.
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