Interview with an Alzheimer’s expert Part III: The genetic component

September 21, 2010 by  

My mother died of pneumonia at the age of 76 but she suffered from dementia during the last 10 years of her life. Doctors thought she had Alzheimer’s disease (AD) but since no autopsy was ever performed, the diagnosis was never confirmed. I come from a family with no history of cancer or heart disease. But there is this possibility of AD that hangs over my head. Last week, we addressed several questions about AD to Dr. Michael Rafii of the Memory Disorders Clinic at UCSD Perlman Ambulatory Care Center in La Jolla, California and of  the University of California, San Diego. Today, I bring you the last part of this Q & A.

Today, Sept 21 is World Alzheimer’s Day.

QUESTION: There is a genetic component to Alzheimer’s. Yet, genetic markers for Alzheimer’s have yet to be identified. What makes Alzheimer’s so complex that it is extremely difficult to find genetic and biomarkers and treatment for the disease?


AD is most likely due to a combination of genetic susceptibility and environmental influence. Early-onset AD is a rare form of AD, affecting only about 5 percent of all people who have AD. It develops in people ages 30 to 60.

 Some cases of early-onset AD, called familial AD (FAD), are inherited. FAD is caused by a number of different gene mutations on chromosomes 21, 14, and 1, and each of these mutations causes abnormal proteins to be formed. Mutations on chromosome 21 cause the formation of abnormal amyloid precursor protein (APP). A mutation on chromosome 14 causes abnormal presenilin 1 to be made, and a mutation on chromosome 1 leads to abnormal presenilin 2.

Even if only one of these mutated genes is inherited from a parent, the person will almost always develop early-onset AD. This inheritance pattern is referred to as “autosomal dominant” inheritance. In other words, offspring in the same generation have a 50/50 chance of developing FAD if one of their parents had it.

 Scientists know that each of these mutations causes an increased amount of the beta-amyloid protein to be formed. Beta-amyloid, a major component of AD plaques, is formed from the protein APP.

 These early-onset findings were critical because they showed that genetics were involved in AD, and they helped identify key players in the AD process. The studies also helped explain some of the variation in the age at which AD develops.

 Late-Onset AD

Most cases of Alzheimer’s are of the late-onset form, developing after age 60. Scientists studying the genetics of AD have found that the mutations seen in early-onset AD are not involved in this form of the disease.

 Although a specific gene has not been identified as the cause of late-onset AD, one predisposing genetic risk factor does appear to increase a person’s risk of developing the disease. This increased risk is related to the apolipoprotein E (APOE) gene found on chromosome 19. APOE contains the instructions needed to make a protein that helps carry cholesterol in the bloodstream. APOE comes in several different forms, or alleles. Three forms—APOE ε2, APOE ε3, and APOE ε4—occur most frequently.

 APOE ε2 is relatively rare and may provide some protection against the disease. If AD does occur in a person with this allele, it develops later in life than it would in someone with the APOE ε4 gene.

 APOE ε3 is the most common allele. Researchers think it plays a neutral role in AD—neither decreasing nor increasing risk.

 APOE ε4 occurs in about 40 percent of all people who develop late-onset AD and is present in about 25 to 30 percent of the population. People with AD are more likely to have an APOE ε4 allele than people who do not develop AD. However, many people with AD do not have an APOE ε4 allele.

 Dozens of studies have confirmed that the APOE ε4 allele increases the risk of developing AD, but how that happens is not yet understood. These studies also have helped explain some of the variation in the age at which AD develops, as people who inherit one or two APOE ε4 alleles tend to develop AD at an earlier age than those who do not have any. APOE ε4 is called a risk-factor gene because it increases a person’s risk of developing AD. However, inheriting an APOE ε4 allele does not mean that a person will definitely develop AD. Some people with one or two APOE ε4 alleles never get the disease, and others who develop AD do not have any APOE ε4 alleles.

Do IVF children have increased risk for cancer?

August 17, 2010 by  

The long-term effects of in vitro fertilization (IVF) on the mother and on the child have always been a topic of speculation. Louise Joy Brown, the first person born who was conceived via IVF (used to be called the “first test tube baby”) turned 32 last July and she herself is a mother to a 3-year old who was conceived naturally. Researchers could only monitor and record what they observe and know about Louise and thousands, maybe millions of IVF babies like her as they grow, reproduce and eventually die. Only time can tell whether there are long-term health effects associated with this type of assisted reproduction.

One of the first results on the ongoing observation of IVF children are out – coming from Sweden.

Swedish researchers at the University of Lund followed-up 26,692 children born after conception via IVF between 1982 and 2005. Cancer data were extracted from Swedish Cancer Register and comparison was made between cancer patients who were born after IVF and those were not. The results indicate an increased risk for cancer among those conceived by IVF.

The expected number of cancer cases in the general population is 38. Among the IVF children of the same age, 53 were diagnosed with cancer, equivalent to a 1.42 total cancer risk estimate. The most common forms of cancer diagnosed among IVF children were:

In addition, 6 cases of Langerhans histiocytosis were reported where 1 case is expected.

The researchers ruled out maternal age, number of previous babies delivered, smoking, subfertility, previous miscarriages, body weight and multiple births as the cause of the increased cancer risk. Although, it can be speculated that the mode of conception might play a role, the researchers think this may not be the case.

Instead, factors that should be considered are genetic traits from the parents, many of whom may have had health problems that manifested in the infertility that made use IVF in the first place.

Another factor is the fact that IVF resulted in many multiple births that in return led to preterm delivery. Premature babies have higher risks for health problems than babies born at full term.

In addition, the study only looked at Swedish children, and the Swedish population has relatively lower biodiversity compared to say, the UK or the US where IVF is commonly used as assisted reproduction technique. Thus, findings in these children might not be true in IVF children elsewhere.

The authors are quick to reassure parents of IVF children that although they found “a moderately increased risk for cancer in children who were conceived by IVF”, absolute risks are still very low – less than 1%.

3 cigarettes = 1 mutation

June 28, 2010 by  
Filed under CANCER

We’ve always wondered. How do carcinogens in cigarettes cause cancer? The answer is genetic mutations. And not just one. Or two. Or ten. Or a even hundred. We are talking thousands of mutations – tens of thousands, in fact.

This is according to researchers at Genentech, the biotech daughter company of Roche in California. The researchers compared the genetic status of healthy tissue and a piece of lung tumor from 51-year old male patient who smoked on average 25 sticks of cigarettes per day for 15 years before tumor removal. Using state-of-the art genetic technology that looks at whole genomes rather than a few genes, the researchers were able to find mutations fast. They detected as many 50,000 mutations in the tumor cells.

According to study author Zemin Zhang of Genentech:

Fifty thousand is a huge number. No one has ever reported such a high number… This is likely associated with the smoking history of the patient. It is very alarming.”

Doing some calculations based on the number of genetic mutations and the number of cigarettes smoked over the last 15 years, the researchers estimated one genetic mutation for every 3 sticks of cigarettes smoked. The smoking rate of 25 sticks per day results in about 8 genetic mutations occurring daily.

However, the calculations are actually an oversimplification because they did not take into consideration the defence mechanisms of the body that helps repair damaged DNA. Thus, there could actually be more mutations occurring each day but are rapidly repaired. However, over time, the DNA repair mechanisms become overused and less efficient and can no longer provide ample protection against the damage of smoking. This is when tumors develop.

The patient whose lung tumor was analyzed was a typical lung cancer patient with no unusual characteristics and can therefore represent the average smoker patient diagnosed with cancer of the lung.

“If you imagine over a lifetime you are going to develop this many mutations in the genome, some people may think twice about it.”

The next step is to find out which of these mutations are linked to smoking-related cancer. In the meantime, next time you smoke a cigarette, think of the cells in your lungs and what cigarette smoking is doing to them. Think of those mutations happening each day. Maybe then you’ll be motivated to stop.

The male infertility-cancer link

March 30, 2010 by  
Filed under CANCER

Talk about hitting a man when he is already down. A recent research studyreports that male infertility in younger years may be an indication for increased likelihood of having aggressive prostate cancer later in life. The study looked at 22,562 male patients checked for infertility from 1967 to 1998. The data, which were include in 15 California infertility clinics were crosslinked to data in the California Cancer Registry.  Statistical analysis of the data showed that those who had been diagnosed to have the male factor infertility have the highest risk for high-grade prostate cancer, with a 2.6 times higher likelihood compared to those without the factor.

The authors concluded:

Men with male factor infertility were found to have an increased risk of subsequently developing high-grade prostate cancer. Male infertility may be an early and identifiable risk factor for the development of clinically significant prostate cancer.

The results were published in the journal Cancer. The study was conducted by American researchers from different research institutes, led by a team at the University of California at San Francisco (UCSF).

This is not the first study to link male infertility to male-specific cancer. Previous studies have reported that infertile males have higher risk for testicular cancer than those who have normal fertility. And many experts believe there is a strong genetic factor involve.

According to study author and fertility specialist Dr. Paul Turek, who founded the Turek Clinic in San Francisco:

“Over all, this leads me to think that a common genetic defect, or a defect in an important genetic pathway, may underlie all three and possibly even more conditions in life. The infertility is just the first ’sign’ of the problem. Maybe, infertility is the ‘ultimate’ medical disease of a species and reflects larger issues down the line that are serious enough to have God or Darwin say ‘no more reproduction’ to that individual.”

The infertility-cancer link has some consequences on in vitro fertilization (IVF). Are infertile fathers going through the IVF procedure passing on the infertility and cancer factor to their offsprings? Are there any other health risks related to infertility? Would this line of research eventually lead to the popular use of preimplantation genetic screening?

Depression, sleep problems in children – the latest updates

September 3, 2009 by  
Filed under DEPRESSION

baby-feet2More and more reports are coming on regarding depression among children that it just makes you as parent well – depressed. Below I summarized the latest studies on depression and sleep problems in children:

Study # 1:

15% of preschoolers have “atypically high levels of depression and anxiety“, according to Canadian and French researchers. The researchers looked at 1,758 children in Quebec  and followed them up from age 5 months to five years. The family members were also monitored and interviewed.
The researchers found that some kids are more at risk of developing depression than others and indicators are also evident as early as 5 months. The predictors are:

  • 1st : Difficult temperament as a baby
  • 2nd: Lifetime maternal depression

According to senior author Sylvana M. Côté of the Université de Montréal’s Department of Social and Preventive Medicine

“Our study is the first to show that infant temperament and lifetime maternal depression can lead to a high trajectory of depressive and anxiety problems before school entry. It is critical that preventive interventions be experimented with infants who risk developing depressive and anxiety disorders.”

Study # 2:

Another indicator of depression and anxiety among young children is sleep problems. Although in many cases, poor sleep is mainly due to bad habits and poor sleep hygiene,  in some cases it is an indication of emotional disorders. Italian researchers looked at 322 children between 7 and 11 years old. 112 of the participants have been diagnosed with major depressive disorder but were not taking any medication. 200 of the children did not suffer from depression.

The results of the study showed that 82% of children with depression have sleep problems. Only 5% of children in the control group have similar problems. Specific problems reported were:

  • Insomnia
  • Bedtime difficulties
  • Sleep anxiety
  • Fragmented sleep
  • Tendency to co-sleep with parents

According to author Dr. Flavia Giannotti of Center of Pediatric Sleep Disorders at the University of Rome

“Sleep problems are very common in typically developing children. Even though they are more frequent in toddlers and preschoolers, they affect also school-aged children. What was most interesting about this study was the finding that certain types of comorbid conditions might be especially disruptive on sleep. Therefore, in childhood, considerable attention needs to be paid to the interrelation between sleep patterns and emotional disorders. To ensure the most effective care, parents of sleep-disturbed children are advised to first consult with the child’s pediatrician, who may issue a referral to a sleep specialist for comprehensive testing and treatment.”

Study # 3:

British researchers report that early treatment of sleep disorders in children can actually prevent depression. Results from the twin study suggest that sleep problems are mainly due to genetic factors. In the case of depression however, the role of genetic factors diminishes as the child grows older but the environmental factors take a more important role.

According to author Alice Gregory of the department of psychology at Goldsmiths College in London

“We reported in a study previously, that genes were the most important factor in explaining the association between sleep problems and depression in eight year olds. However, when we examined this issue at age 10, we found that genes were less important in explaining the association and that environmental influences had become more important. This could be because environmental experiences are becoming more relevant as children grow older and could therefore play a role in both sleep problems and depression.”

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The brain activity of the AD gene carrier

May 7, 2009 by  
Filed under ALZHEIMER'S

brainy_peopleIt’s in the genes. And the gene variant is called APOE-4. I am referring to the neurodegenerative disease Alzheimer’s disease (AD), the most common cause of dementia.

And even in early adulthood, this gene variant can already cause some structural and functional changes in the brain that is visible to the experts long before the symptoms become evident.

Researchers from the University of Oxford and Imperial College London have observed changes in the brain activity of healthy people carrying the APOE-4 gene variant. The variant is found in about 1 in every 4 people. Not every carrier will develop AD but those who have inherited one copy from their parents have 4 times higher risk for AD. Those who have inherited 2 copies have 10 times higher risk for AD compared to non-carriers.

Using the functional Magnetic Resonance Imaging (fMRI) technique, the researchers were able to distinguish difference patterns of brain activity between carriers and non-carriers. Specifically, the part of the brain involved in memory, the hippocampus, is shown to be hyperactive in APOE-4 carriers.

According to researcher Dr Christian Beckmann

“Our brains are always active – our minds wander even when we’re not carrying out specific tasks. We were surprised to see that even when the volunteers carrying APOE4 weren’t being asked to do anything, you could see the memory part of the brain working harder than it was in the other volunteers. Not all APOE4 carriers go on to develop Alzheimer’s, but it would make sense if in some people, the memory part of the brain effectively becomes exhausted from overwork and this contributes to the disease. This theory is supported by studies that have found the opposite pattern in people who have developed Alzheimer’s, with these people showing less activity than normal in the memory part of the brain.”

Similar findings have been reported by researchers at the Medical College of Wisconsin. Again using fMRI, the American researchers investigated the function of the hippocampus and the posterior cingulated cortex. These two brain structures are important for memory processing, especially information acquisition, filtering and sorting.

Offsprings of AD patients who are symptomless but nevertheless carry the APOE-4 gene variant exhibited significantly reduced (35% less) functional brain connectivity between the two previously mentioned brain structures.

The genetics behind AD is slowly becoming clear. So is the link between the gene variant and brain functioning. However, what still needs to be clarified is why some APOE-4 carriers develop full blown AD and some don’t. Surely it cannot be ruled out that environmental factors (e.g. lifestyle) may play a role.

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What about cancer resistance?

February 23, 2009 by  
Filed under CANCER

Two people. One smokes, the other a lifetime non-smoker. So why is it that the non-smoker develops lung cancer and the smoker doesn’t? Is it pure luck? Is it simply one of life’s ironies? Or is there a scientific explanation behind it?

The majority of research studies in oncology investigate what makes people susceptible to cancer. Most researchers look at susceptibility genes and risk factors. This is understandable because millions of people worldwide have cancer. Cancer is a major cause of mortality and the rates are rising: cancer is predicted to be the number one killer globally in the coming decade.

But what about the millions who do not get cancer? For every cancer victim, there are two people who escape the disease. Even some of the heaviest smokers don’t get lung cancer while the most health-conscious people do fall prey to this cruel disease. What do these cancer-free people have that the others don’t? Is this a matter of chance, or are there cancer-resistant genotypes?

Swedish professor George Klein is busy with a field of research in oncology that is neglected, almost overlooked – cancer resistance. He recently published a paper called “Toward a genetics of cancer resistance” in the Proceedings of the National Academy of Sciences.

In the course of his research, Klein has hypothesized five protective mechanisms that may protect people from cancer, namely:

  • Immunological mechanisms. Individuals may differ in terms of immune system efficiency.
  • Genetic mechanisms. Some people have more effective DNA repairing system than others. Those with specific DNA repair deficiency can develop certain types of cancer.
  • Epigenetic mechanisms. Genetics involve the DNA itself while epigenetics involve gene expression. Different gene expressions can have different results.
  • Intracellular mechanisms. This involves apoptosis or cell death, a defense mechanism within the cell itself. Apoptosis is triggered in some people but not in others.
  • Intercellular mechanisms. The researchers believe there is a defense mechanism that makes cells watch their neighbors and sound the alarm when precancerous conditions are detected.

Klein is urging researchers to look into cancer resistance as well and not only into cancer susceptibility.

Evolution seems to have favored some relatively common resistance genes that protect the majority of humans against cancer development. One day, finding out how nature keeps most of us cancer-free could help identify and repair specific genetic mechanisms in the large minority of individuals who do suffer from cancer. However, …[according to the author] it’s premature to speculate exactly how understanding genetic resistance could help people who are susceptible to cancer.


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Personalized genetic information and risk assessment for heart disease

November 25, 2008 by  


The traditional method of assessing risk for heart disease has been useful for prediction at population level but loses its predictive power at the individual level.

Recently, the use of genomics in medicine has gained a foothold. I summarize two studies here that demonstrated this.

Genetic variants for sudden cardiac arrest

A recent paper reviewed genetic variants that cause sudden cardiac death (SCD). More than 300,000 people die in the US each year as a consequence of SCD. Most of these deaths are related to underlying heart conditions such as coronary heart disease (CHD). The paper, too, points out the shortcomings of the traditional risk assessment methods.

The conventional coronary risk factors and presence of congestive heart failure are associated with SCD in the general population but have poor ability to predict SCD at the individual level because of their prevalence and comparatively modest effects on risk.”

Some conditions, characterized by structural heart problems are found to be mostly due to genetic mutations. These conditions include:

  • Hypertrophic Cardiomyopathy
  • Arrhythmogenic Right Ventricular Dysplasia
  • Dilated Cardiomyopathy
  • Inherited Arteriopathies

The study concluded:

Developing an understanding of genetic contributions to SCD may prove important in the management of genetic SCD syndromes, the development of novel therapeutics, and risk stratification in the general population, thereby improving our ability to predict and ultimately prevent this tragic outcome.

Genetic variants for coronary heart disease

This new study by researchers at the Baylor College of Medicine in Houston demystifies the genetics of CHD. According to the study

identifying a single, common variation in a person’s genetic information improves prediction of his or her risk of a heart attack or other heart disease events and thus, choice of the best treatment accordingly.”

The DNA variation that the researchers pinpointed at the 9p21 chromosomal region is not a mutation. It is a genetic variant, which means that each of has it, but slightly different in each individual.

The study looked at 10,000 middle-aged Americans as part of the Atherosclerosis Risk in Communities research. Study participants were classified based on traditional risk factors as follows:

  • Low risk participants are those having a less than 19% chance of having coronary heart disease (CHD) in the next decade.
  • Intermediate risk participants are those with a 10 to 20% likelihood to have CHD in the next ten years.
  • High risk participants are those with the likelihood of 20% or more to have CHD in the next 10 years.

Looking at the genetic information, however, gives a completely different picture. Many of the participants with the genetic variant had risk profiles higher than initial categorization and had to be reevaluated. Those who have intermediate risk profiles are especially affected because they could easily move up the risk ranking.This recategorization improved risk prediction, leading to more optimal preventive measures and treatment.

Recently, personalized genetic information has gone mainstream as more and more companies are offering their services at affordable prices. The start up company 23andme is now offering “retail DNA test” for only $399.00.

But does it really help in the diagnosis and treatment of diseases? It seems that it does, in certain cases, as demonstrated by the review studies above. The 23andme test can supposedly screen for over 90 traits which can reveal a person’s predisposition to certain diseases.

Is personalized medicine up next?

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Genetics in heart disease treatment and diagnosis

September 24, 2008 by  

We are in the age of genomics. It is now possible to have our genome checked for predisposition to genetically-linked diseases such as cancer, Alzheimer’s, and yes – cardiovascular disease.

According to a review paper in 2005:

Genetic studies provide new insights into the pathogenesis of coronary artery disease and myocardial infarction. Future studies will focus on identification of new disease-causing genes and susceptibility genes, exploration of the molecular mechanisms by which mutations cause coronary artery disease/myocardiaI infarction, and gene-specific therapies for patients.”

It’s been three years. Are we ready yet for genetic-based treatment of heart disease? Let’s take a look at what the latest research on genetics say.

First gene therapy on trial

The first clinical trial of gene therapy for the treatment of heart failure was launched earlier this year.

Gene therapy is a technique for correcting defective genes responsible for disease development by inserting genes into a patient’s cells and tissues. In most gene therapy studies, a “normal” gene is inserted into the genome to replace an “abnormal” disease-causing gene.

In this therapy developed by researchers at the New York-Presbyterian Hospital and Columbia University Medical Center, the gene SERCA2a is injected into the patient with the hope that gene facilitates the replenishment of enzymes necessary for efficient heart pumping. In patients with heart failure, SERCA2a is depressed, leading to insufficient pumping of the heart and eventually heart failure.

Genetic fingerprinting for cardiomyopathy

Dilated cardiomyopathy is a condition where the heart is abnormally large so that the heart cavity is enlarged and stretched. This weakens the heart, making pumping inefficient and can eventually lead to heart failure. 36% of all cases of dilated cardiomyopathy is due to excessive alcohol consumption. However, distinction between alcohol-induced and non-alcohol induced cardiomyopathy is not an easy task. Because denial is one of the most common symptoms of alcoholism, self-reported evaluations are not reliable sources of data for prevention, diagnosis and control.

Researchers at the Boston University School of Medicine may just have found the answer. They report that they identified the “genomic ‘fingerprint’ for alcohol-induced heart failure.”

According to the authors,

now that we have this diagnostic marker or fingerprint, clinicians will be better able to monitor the progress of a patient who is being treated either medically or simply self reporting a cessation of drinking.”

Genetic markers for heart disease

In recent years, the search for genetic markers for human diseases has been stepped especially in the fields of oncology, neurodegenerative disorders, and cardiovascular medicine. Recent studies report about promising candidate genes that are strongly linked to the development of coronary heart disease and heart attack. However, these techniques are mainly experimental and still not part of standard clinical practices to diagnose and treat cardiovascular disorders.

How much more time do we need till we get there? It’s hard to say. It seems that medical science is making progress but progress is not that fast. Let’s touch base again in a couple of years.

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Some Pertinent Facts About Hip Arthritis

January 29, 2008 by  
Filed under ARTHRITIS

Greetings .. Gloria is away this week, and will resume posting on February 4, 2008. In the meantime, please enjoy this article about Hip Arthritis. // HART

When a person suffers from hip arthritis, he or she will, under most circumstances, suffer from a condition known as osteoarthritis which is a very common form of hip arthritis, and which is sometimes also known as wear-and-tear arthritis and even degenerative joint disease. This form of hip arthritis is characterized by gradual damage to the cartilage of a person’s joints and when the cartilage that protects the joints becomes worn out due to such a form of arthritis, the bones become exposed in the person’s joints resulting in a great deal of distress.

Affects Persons That Are Fifty Years Of Age Or Older

Though anyone can suffer from hip arthritis, it is normally associated with persons that are fifty years of age or older, and the problem is also more commonly seen in patients that are overweight, and also that when the same person begins to lose weight there is a gradual improvement in the condition and symptoms of hip arthritis start to fade away. Doctors also believe that hip arthritis can be caused due to genetics and so if you belong to a family in which someone has this form of arthritis, then you could also be at risk of suffering from the same.

There are certain other factors too that can cause a person to suffer from hip arthritis and these include having trauma with the hip and even because of fracturing of bones that are located close to joints. There are certain symptoms that you will notice if you are suffering from hip arthritis and these symptoms tend to get worse as the condition deteriorates further. However, it is also not the case that the symptoms will become worse with the passage of time and it can occur that a patient has some months that are good as far as their condition is concerned, while other months may turn out to be bad, and symptoms may also are affected because of changes in the weather conditions. Thus, hip arthritis symptoms noticed on a particular day may not appear on other days, and they may also not be an accurate representation of the way in which the condition is progressing.

Common symptoms of hip arthritis include pain when performing activities, limitation to how much a person can move about, hips becoming stiff and needing to limp while walking. It is also recommended to get treated as soon as the symptoms appear, and the treatments can either are very basic in some instances, while other instances may even warrant surgery to be performed. In any case, you will need to get expert medical advice to know what the best treatments for your particular case of hip arthritis warrants.

Two Genes Related to Ankylosing Spondylitis, Discovered

October 25, 2007 by  
Filed under ARTHRITIS

A disabling form of arthritis, ankylosing spondylitis is a painful and progressive disease in which some or all of the spine’s vertebrae fuse together.

Ankylosing spondylitis is a type of arthritis that not only affects the spine but also can attack other joints and organs, including the heart, lungs and eyes. The condition afflicts an estimated one in 200 males and one in 500 females and typically strikes during adolescence and young adulthood.

Now, an international team of researchers (led by a Fred Hutchinson Cancer Research Center geneticist) has discovered two genes associated to ankylosing spondylitis.

The study revealed two genes linked to ankylosing spondylitis: ARTS1 and IL23R, both of which influence immune function. Together with the previously known gene HLA-B27, the new findings increase to three the number of genes known to be involved in the disease. A person who carries all three genetic variants would be expected to have a one-in-four chance of developing the disease.

What does finding a gene associated to a disease mean actually? It means that anybody can get tested for said genes to determine their risk of a certain disease — such as ankylosing spondylitis and the genes associated with it as recently discovered. In the long run, this disease may be treated or prevented by gene therapy, once research become successful in this department.

Indeed, genes are important, as my friend Hsien always tells us.

According to principal investigator and corresponding author Lon Cardon, Ph.D (a member of the Hutchinson Center’s Human Biology Division, a statistical methodologist who last year came to the Hutchinson Center’s Human Biology Division from the University of Oxford, where he conducted the research and retains an academic post, also a professor of biostatistics at the University of Washington):

“Clinically these diseases tend to occur together — people with inflammatory-bowel disease also tend to have a higher probability of having ankylosing spondylitis and psoriasis. The IL23R gene provides a genetic link that sheds new light on their co-occurrence.

This is an exciting time for genetics. The Wellcome Trust Case Consortium has yielded more genetic discoveries for common diseases in 2007 than have been made in the entire history of the field.”

Do not get tired ever of hearing about genetics and stuff in any other disease or health condition, because the breakthroughs are admirable, not to mention awesome. Not all people (not even me!) may understand it and the research involved, but it is paving the way to prevention and cure of serious diseases. Yes, including arthritis and its many forms such as ankylosing spondylitis.

Ankylosing spondylitis. What a mouthful! But now we know that it is a form of arthritis.

Find more details from the Fred Hutchinson Cancer Research Center press release.

Grandparents Use DNA Analysis to Prevent and Treat Inherited Diseases for Future Generations

April 4, 2007 by  
Filed under CANCER

By Scott Nizborski

Why is DNA Analysis important to me?

Knowing your family’s genetic history may someday save your life or that of someone you love. Based on state-of-the-art genetic technology, a unique DNA Profile can be generated for you to keep for years to come. DNA Storage for up to 25 years is available for future genetic testing, upon your request. What better gift can a loved one leave behind?

What role does DNA have in Funeral Service?

The purpose of this article is to familiarize Funeral Directors about DNA activities, and related areas. Realizing that this technology is what we as caregivers are used to discussing, is a field that is of concern to many of our clients and their families. The vast spectrum of DNA can give us insight on the value it can play in our community. In a series of articles, we would like to give you a basic knowledge about the different but related studies involving DNA.

It takes three generations to determine predisposition to most of the genetic inherited diseases / disorders. It is now known that families should store DNA for future use. Banking specimens containing DNA from the same Family provides invaluable information for the health of current and future offspring. We as Funeral Directors have an opportunity to make a Family aware that such a service is available. After burial, retrieving DNA can be expensive. Obtaining DNA after cremation is much more difficult. The success rate of recovering DNA within the first year of cremation is approximately 50%. Offering storage and or profiling DNA of the deceased, gives Funeral Directors a Unique opportunity to offer a Service that can have a lasting impact on those we serve. If you as a Funeral Director do not see the need for this service, it does not mean that families do not need this service. Statistics tell us that families place a tremendous amount of trust in their Funeral Director. This is because we care so deeply in what we do. Informing a Family of their options, while guiding them through the most difficult times in their life is a responsibility that a Funeral Director accepts and excels in.

It is our hope that Funeral Homes throughout the United States will contact us and give us their input as to the value of DNA in a Funeral service.

Why we firmly believe in what we do.

At the National Funeral Directors Association meeting in October 2001, we outlined all the reasons for the value of DNA storage such as paternity/inheritance, genealogy, missing persons, forensic issues; identification of hereditary disorders, congenital birth defects; predisposition to allergies, mental, metabolic, cardiovascular, bleeding/clotting disorders, genetic cancers, microbial diseases. The potential does not end with the above. Rapidly evolving technologies in cloning pets, stem cell/gene therapy are currently being done, all to improve the quality of life.

Recently we had four interesting success stories…

1. A 62-year-old female dies of complications resulting from Breast Cancer. The deceased women leave 2 daughters and 1 granddaughter. During a “Pre-Need Consultation”, the woman elected to have her DNA profiled and the sample banked.

2 years later; one of the daughters is diagnosed with the same Breast Cancer as the Mother. The second daughter has her DNA profiled and compared to the mothers. It is determined that the second daughter does not have the same genetic structure as the mother that would pre-dispose her to the cancer. However, the Granddaughters DNA is profiled and it is determined that she possesses the same genetic disorder as the Grandmother. Pharmacogenomics and gene therapy are begun to prevent the cancer in the granddaughter before it develops.

2. The mother of a Divorced son was interested in identifying the granddaughter’s father. Was he her husband were her son? We identified her son is the alleged father. This was a “Paternity” issue.

3. The three sons of the deceased lady came to request identification of their mothers remains between two occupants of a gravesite that had collapsed. She passed away seven years ago, so the atypical specimen sources were bone marrow and vertebrae. Procedures were laborious, but we identified their mother. Her remains can now be transferred to another site. This is “Profiling”.

4. A friend’s baby presented with what appeared to be a Bleeding tendency at 3 months of age. The baby was admitted to Children’s Hospital, Cincinnati, extensively treated but expired at age 8 months. An autopsy revealed universal capillary involvement (small blood vessels) by a clotting abnormality resulting in damaging complications in vital organs such as heart, liver and spleen. This leaves a Protein called von Willebrand factor and is coded by a Gene called ADAMSTS 13. The parents are currently being tested for “Mutations” in order to know who transmitted to the gene. The baby’s DNA is currently in storage it doesn’t matter who stores DNA in life and in death provided it is properly collected and stored because although it’s stable, it can be contaminated and it can disappear during purification; this complicates genetic testing. Before the advent of Pharmacogenomics, astute clinicians treating HIV patients relied on drug resistance testing to predict outcomes; complementary to resistance testing his current genotyping, which includes identifying mutations, associated with resistance. In the not-too-distant future, the combination of drug resistance testing and pharmacokinetic testing will provide a better idea of in-vivo relevance of resistance data. Stored DNA lasts forever; it will provide an endless source for multiple testing that will hopefully improve clinical outcomes.

The terms “Pharmacogenomics” and “Pharmacokinetics” are sometimes used interchangeably to describe the analysis of genes involved in drug response.

Pharmacogenomics is more inclusive; it refers not only to the effects of individual genes, but also to complex interaction between genes from every part of the genome affecting drug response.

Pharmacogenomics is an aid to diagnosis and prognosis. Routine diagnosis is not always straightforward. A patient does not always come with textbook type symptoms of the disease. In some cases, a single gene variation has been shown to be responsible for disease, and a Genetic test for this scan confirms the diagnosis as in cystic fibrosis and Huntington’s disease. Sometimes more than one gene is involved, such as to Breast Cancer genes, Alzheimer’s Disease genes, and susceptibility to Migraine genes. The most likely publicly visible contribution of Pharmacogenomics to improved health care would be delivery of a number of drugs coupled to diagnostic tests based on genetic markers for head and neck, pancreatic cancers, and solid tumors.

Pharmacogenomics classifies patients into responders and non-responders to particular therapeutic options. Breast cancers that over express a Protein for the herceptin genes are candidates for monoclonal antibody therapy. The cholesterol-lowering drug PRAVACHOL works according to the number of copies of the transfer protein gene. HIV Phenotyping is an important and practical adjunct to the treatment of AIDS.

Pharmacogenomics can save lives lost to adverse drug events, the 6th leading cause of death in the US. A blood test now enables physicians to tailor a certain drug dosage to their patient’s genetic profiles. However, the cause and effect association remains unknown. Implementation of rapid automated DNA genotyping capabilities still, over time, provides individual genotypes of patients. Clinical data that is properly collected and managed identifies patient subpopulations at risk for adverse events, while allowing others to continue to receive the benefits of pharmaceutical therapy.

Pharmacogenomics and Gene Therapy
Mutation is a change of DNA sequence leading to aberrant or absent expression of the corresponding protein. It is the mutation, not the gene that causes predisposition to disorder/disease. Polymorphism is the quality of existing in several different forms. Sequencing of parts of the genome has demonstrated that some of these polymorphisms are in genes whose functions are important in responses of individual patient to therapy. The pathologist will need to profile common polymorphisms in patients who are beginning therapy for common diseases such as diabetes, hypertension, cancer and infections. The laboratory definition of the genotype/phenotype will determine the specific drug and doses suitable for him. This puts the pathologist in a more definitive position to determine appropriate therapy than traditional predictions of disease behavior based on morphology of lesions (microscopic patterns) or cultural characteristics of infectious organisms. The lab also monitors the success of gene therapy. After a gene is introduced, the tissue where the gene is inserted (i.e.: Transgenic Monkey or Mouse) must be active and should be monitored for normal expression of the introduced gene and normal structure and function of the gene product. The lab must also monitor the “integrating transfected genes” such that integration allows both normal gene expression and does not produce abnormal function or structure of the patient’s other genes. In summary, molecular pathology is permeating and penetrating, as was immunopathology 20 years ago. “Immunopathology” an example of which is vaccine therapy is nothing new, a German/Austrian vaccine “UKRAIN” is supposed to destroy cancer cells through APOPTOSOS (programmed cell death) without attacking healthy cells. The US now has “GLEEVAC” with identical results. It also has been proven that in breast cancers there are genetically divergent CLONES that account for different microscopic components resulting in different responses to therapy.

Future Direction
As the human genome Project continues to uncover important disease genes (especially those for common disorders) at an ever increasing rate and technologies for high-speed DNA sequencing and multiplex mutation detection continued to improve, we can anticipate diagnostic molecular genetics assuming a far more dominant role in public health and preventive medicine. The advance of DNA “CHIPS” containing thousands of probes may someday allow extensive genotyping and lifetime disease prediction for thousands of disorders from a single drop of blood. Also, a poster on Human Genome Landmarks in the US Department of Energy, identifies a whole gamut of diseases/disorders with the corresponding position of the defective gene! Against these promising advances will have to be weighed ethical issues, especially in the field of gene therapy. Whatever the ultimate balance reached, there’s no doubt that molecular genetics will be the driving force behind an ever greater proportion of evidence based medical practice in the 21st century and virtually every patient whether healthy or ill will feel the impact.

The impact of DNA storage on clinical practice Evidence based medicine is the gold standard for the 21st century.

What do we do that contributes to the practice of this medicine? What specific examples and daily living indicate that storing DNA is a “Must”?

The event of 9/11 mainly profiling and identifying the deceased was laborious and expensive on federal funds despite which only approximately 2000 persons have been identified. One does not realize the importance of the death certificate without which burial cannot be accomplished until death occurs! Soldiers “missing in action” cannot be declared dead until their bodies are found and identified.

An article in USA Today concerned a “Mystery killer” that involved a young couple; studies failed to give a definitive answer despite autopsy and numerous laboratory tests. Since chances that the suspected disease that clinically presented to be contagious (plague) proved negative on repeated testing. Had DNA been stored, further testing may have led to the diagnosis and cause of death

A TV program about a Serial killer in Juarez Mexico led to more than 200 missing women and “no leads”. Profiling and storing of DNA when these women were newborns would have helped identify the remains that took months to surface. The women after being raped were doused with gasoline and burned! The problem is ongoing.

Although Chandra Levy was missing for a year before the body was found, DNA is stable, and after profiling samples from her remains she can now be laid to rest. Since degraded DNA is difficult to purify, tests on her remains are ongoing to hopefully identify the killer. The FBI in USA Today declared, “there still are no clues to the killer”. Samples are from her remains such as hair, teeth, bone; even old blood can still be stored and tested along with a Suspect’s samples until results are conclusive.

A complex disease such as Parkinson’s disease and the genes whose polymorphic forms can increase any person’s risk but not necessarily cause it is the second most common in a Neuron-degenerative disorder. Parkinson’s disease has neither a Polygenic (multiple genes) or multifactoral (genes and environment) cause. Over the past few years, debate has occurred between Parkinson’s disease having a Genetic component or is just secondary to environmental influences. To evaluate the possible genetic component, open quote gene mapping” is the way to go. The availability of data from the Human Genome Project is opening new possibilities in studying common diseases such as Parkinson’s disease. The multitude of molecular techniques and statistical tools applied to this data now allows us to potentially move medicine from a “reactive” discipline to one that can prevent disease. However, once found, how these “susceptibility genes” will be used in the future remains to be seen.

A newborn (the 3rd child) was diagnosed to have a “Rare protein allergy”. Surgery was successful the baby is now seven years of age and healthy. Two other siblings are healthy. Storing this baby’s DNA would have enabled testing of future siblings for mutations related to this rare congenital predisposition to allergies.

At three months of age a Baby presented with a Bleeding disorder; she was admitted, traded and died at the Children’s Hospital in Cincinnati. The baby’s profile showed a defective ADAMSTS 13 gene. The parents are being tested for this “mutation” and the baby’s blood, buccal smears, and hairs are stored.

Will everyone be gene type early in life to prevent disease that they are at risk for? How will this affect employment/applications for competitive educational opportunities? Wolf farm code genetic genotyping be routine to determine patients with the risk for side effects or variability in efficacy? If the patient refuses typing will third-party payers is still pay for medications and/or treatment? Someday mandatory DNA storage and testing in life and death will enhance the quality of life and improve clinical outcomes because increasing knowledge of genetic variations sheds light on the role of genetic and environmental factors and disease susceptibility, aggression and therapeutic response.

Specialists can now screen eggs for the faulty gene that closes early onset Alzheimer’s disease, enabling women who carry their rare disorder to avoid passing it on to their children.

FDA approved GLEEVEC has been very effective in chronic myelogenous leukemia and rare (stromal) stomach cancers; causes of relapse do so because they have developed mutations that alter GLEEVEC’s target site in the leukemic cells, a Phenomenon well known to infectious disease clinicians. Just as microbes developing drug resistance mutations, so do cancer cells.

Summarizing the future of cancer treatment: in the past, pathologic diagnosis was based on histology. In the future it will be based on molecular profiling of tissue both that the genetic and proteinomic level. In the past, therapy was chosen by disease category. In the future, combination therapy will be aimed in tailored to individual patient profiles or classes of profiles. Select, monitor, and reevaluate.. that’s hope for the future!

Scott Nizborski is the President and Owner of LabEx, Inc. LabEx is an authorized represetative for DNA Analysis providing DNA Profiling and Storage Services focused on the Funeral Pre-Need business.

Article Source:

Genetic Technologies Reports Breakthrough in the Genetic Basis of Drug Addiction

March 16, 2006 by  
Filed under ADDICTION

3/14/2006 9:24:00 AM EST

Genetic Technologies Limited (“GTG”) (Nasdaq:GENE) (ASX:GTG) is pleased to refer to a “breaking news” item released in London yesterday by BBC News. BBC reported a significant breakthrough had been made in understanding the genetic basis of cocaine addiction, quoting a scientific paper just published online by the prestigious Proceedings of the National Academy of Science (“PNAS”).

The report announced a genetic variation had been identified which could significantly increase the risk of an individual developing cocaine addiction or dependence. The discovery also validates the logic of a new basis for the design and use of novel drugs to treat cocaine abuse in the future.

The BBC article stated that this research was funded by the British Medical Research Council.

What is especially relevant to GTG stockholders is that this research was in fact co-funded by GTG, that the genetic variations identified by this project are non-coding, that new patents have just been filed on the relevance of these genetic variations to cocaine addition and that GTG has secured world-wide exclusive rights to commercialize these new discoveries. Indeed, this whole project arose from the foresight of King’s College London, who took a license to the GTG non-coding patents in 2004.

This project is yet another example of the original GTG non-coding patents today spawning new research, new discoveries and new patents and creating new opportunities for GTG into the future.

By way of further background information, the UN Office for Drug Control estimates the number of illegal drug users now exceeds 150 million worldwide. However, other studies suggest this is an under-estimate. Until now, the global pharmaceutical industry has not made treatment of substance abuse a priority. The current market is estimated to exceed US$1.1 billion, and is expected to grow to US$1.3 billion by 2008. Industry experts see this market as having great potential. It is also an area where fundamental patents are likely to prove extremely valuable, especially when combined with new genetic testing methods (genotyping), which will permit cheap and efficient whole genome scanning for susceptibility to cocaine addition.

About Genetic Technologies Limited

Genetic Technologies was an early pioneer in recognizing important new applications for “non-coding” DNA (DeoxyriboNucleic Acid). The Company has since been granted patents in 24 countries around the world, securing intellectual property rights for particular uses of non-coding DNA in genetic analysis and gene mapping across all genes in all multicellular species. Its three-pronged business strategy includes: 1) the global commercialization of its patents through an active licensing program; 2) the expansion of its dominant commercial genetic testing business in Australia; and, 3) the commercialization of its various research and development projects aimed at generating further intellectual property of global commercial significance.

This announcement may contain forward-looking statements within the meaning of Section 27A of the U.S. Securities Act of 1933 and Section 21E of the U.S. Securities Exchange Act of 1934 with respect to the financial condition, results and business achievements/performance of Genetic Technologies Limited and certain of the plans and objectives of its management. These statements are statements that are not historical facts. Words such as “should,” “expects,” “anticipates,” “estimates,” “believes” or similar expressions, as they relate to Genetic Technologies Limited, are intended to identify forward-looking statements. By their nature, forward-looking statements involve risk and uncertainty because they reflect Genetic Technologies’ current expectations and assumptions as to future events and circumstances that may not prove accurate. There is no guarantee that the expected events, trends or results will actually occur. Any changes in such assumptions or expectations could cause actual results to differ materially from current expectations.

Genetic Technologies Limited Dr. Mervyn Jacobson or Tom Howitt, +61-3-9415-1135 or Investor Relations Contacts: Lippert/Heilshorn & Associates Kim Sutton Golodetz / Lisa Lindberg, 212-838-3777 / or Bruce Voss, 310-691-7100

© 2006 Genetic Engineering News, All Rights Reserved

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