Ten genes for human growth

Ten new genes related to human growth have been discovered. The meta-analysis, published in the May 2008 of Nature Genetics, is based on data from more than 26,000 study participants. It verifies two already known genes, but also discovered ten new genes. Altogether they explain a difference in body size of only about 3.5cm.

The analysis produced some biologically insightful findings. Several of the identified genes are targeted by the microRNA let-7, which affects the regulation of other genes. This connection was completely unknown until now. Several other SNPs may affect the structure of chromatin, the chromosomesurrounding proteins. Moreover, the results could have relevance for patients with inherited growth problems, or with problems in bone development, because some of the newly discovered genes have rare mutations, known to be associated with anomalous skeletal growth.

The total number of known “height genes” now amounts to 26.

Further functional studies are necessary to completely elucidate the biological mechanisms behind this growing list of genes related to height.  

Simple blood test may detect lung cancer  

A simple blood test may be able to detect lung cancer in its earliest stages with unprecedented accuracy, according to new research presented at the American Thoracic Society’s 2008 International Conference in Toronto on 20 May.

The possibility of developing a non-invasive test to distinguish cancerous from benign lesions in the lungs has enormous implications for medicine.

“CT screening results in the detection of lung nodules in 20% to 60% of subjects,” said Anil Vachani, MD, Assistant Professor of Medicine at the University of Pennsylvania. “This high false-positive rate requires patients to undergo extensive follow-up investigations, such as serial CT scans, PET scans or biopsies. This test may be able to obviate the need for such things if it is developed into a large scale diagnostic tool.”

Because lung cancer is a very diverse disease, screening for it can be very difficult. The researchers hoped to identify a stable and consistent way of determining the presence of lung cancer by testing for the gene expression of white blood cells.

Rather than screening for factors released by the incipient tumour into the blood stream, the test Dr Vachani and colleagues used looked at gene expression in the subject's own circulating white blood cells. “We found that the types of genes present in these cells could tell us whether or not cancer was present,” explained Dr Vachani.

To test the accuracy and validity of the method, the researchers recruited 44 patients with early stage lung cancer and 52 control subjects who were matched for age, smoking status, gender and race. They then used a number of genetic arrays to determine the best targets for detecting the presence of cancer. They found that a 15 gene array had the highest accuracy, at 87%.

“These findings suggest that lung cancers interact with circulating white blood cells and change the types of genes that are active in these cells. This finding can be potentially used to develop a non-invasive diagnostic test for patients suspected of having lung cancer,” said Dr Vachani. “A diagnostic test that could more accurately determine the risk of cancer in patients would be extremely valuable and have very important economic implications by reducing unnecessary surgery, biopsies and repeated imaging tests.

“We are planning to perform validation studies to further evaluate the utility of this approach for diagnosing lung cancer in a larger population,” said Dr Vachani. “If our results are encouraging, we would like to test this in a prospective clinical trial.”  

Gene sequence map of large structural variation  

Researchers in the US have produced the first sequencebased map of large-scale structural variation across the human genome. The work, published 30 April 2008 in the journal Nature, provides a starting point to examine how such DNA variation contributes to human health and disease.

Other recently created maps, such as the HapMap, have catalogued the patterns of small-scale variations in the genome that involve single DNA letters, or bases. However, the scientific community has been eagerly awaiting the creation of additional types of maps in light of findings that larger scale differences account for a great deal of the common genetic variation among individuals and between populations, and may account for a significant fraction of disease. While previous work has identified structural variation in the human genome, a sequence-based map provides much finer resolution and location information.

Large-scale structural variations are differences in the genome among people that range from a few thousand to a few million DNA bases. Some are gains or losses of stretches of genome sequence. Others appear as re-arrangements of stretches of sequence. Already, some structural variations have been linked to individual differences in susceptibility to the human immunodeficiency virus (HIV), risk of coronary heart disease, as well as to schizophrenia and autism. Researchers hope the new map will open the door to uncovering the functions of structural variants in even more conditions.

Sequence data from the structural variation map are publicly available through the US National Institutes of Health National Center for Biotechnology Information Trace Archive, www.ncbi.nlm.nih.gov/Traces. Mapping data are also freely available from the University of Washington, hgsv.washington.edu


Gene sequence linked to overweight, obesity  

A gene sequence that is linked to overweight and obesity and a tendency to develop type II diabetes has been described as part of a study published in the 4 May 2008 issue of Nature Genetics.

Scientists from Imperial College London, University of Michigan, USA, and the Pasteur Institute, France have discovered that the sequence is associated with a 2cm expansion in waist circumference, a 2kg gain in weight, and a tendency to become resistant to insulin, which can lead to type II diabetes. The sequence is found in 50% of the UK population.

The study also shows that the gene sequence is a third more common in those with Indian Asian than European ancestry. This could provide a possible genetic explanation for the particularly high levels of obesity and insulin resistance in Indian Asians, who make up 25% of the world's population, but who are expected to account for 40% of global cardiovascular disease by 2020.

The new gene sequence sits close to a gene called MC4R, which regulates energy levels in the body by influencing how much we eat and how much energy we expend or conserve. The researchers believe the sequence is involved in controlling the MC4R gene, which has also been implicated in rare forms of extreme childhood obesity.  

Researchers identify gene that causes enlarged heart  

A gene that can cause the heart to become enlarged, greatly increasing the risk of heart attacks and heart failure, has been identified in a study published in the journal Nature Genetics (28 April 2008).

The research reveals how a gene called osteoglycin (Ogn), which had not previously been linked with heart function, plays a key role in regulating heart growth. The study suggests that the gene can behave abnormally in some people, and that this can lead to the heart becoming abnormally enlarged.

The study shows that Ogn regulates the growth of the heart's main pumping chamber, its left ventricle. If the left ventricle thickens, this creates a condition known as elevated Left Ventricular Mass (LVM), a major contributing factor for common heart diseases. When the heart is enlarged it needs more oxygen and becomes stiff. This can cause shortness of breath or lead to a heart attack.

The researchers found that higher than normal levels of Ogn were associated with the heart becoming enlarged in rats and mice and in humans.
 

The researchers, from Imperial College London, the Medical Research Council (MRC), and other international institutions, hope that their findings will provide new avenues for treating people who either have an enlarged heart or are at risk of developing one. At present enlarged hearts can only be treated by lowering blood pressure.  

Researchers find gene for epilepsy  

Researchers in Victoria, Australia have developed a new genetic test to help predict the response of epilepsy sufferers to commonly used drug treatments. The noninvasive blood-based test has been developed by doctors from the Royal Melbourne Hospital, Melbourne University and the Murdoch Children's Research Institute.

Epilepsy is one of the most prevalent and serious disorders of the central nervous system with an estimated prevalence of approximately 50 million cases worldwide.

Carbamazepine and valproate, two first-line treatments for epilepsy, have limited efficacy, with 40% of patients having a significant adverse drug reaction and 20- 40% experiencing recurring seizures.

This new genetic test will tell doctors whether their patients are genetically predisposed to respond to the medication, which will allow them to more effectively target treatment and care.  

Metastasis for breast tumours to the lung  

The identification of five genes involve in the metastasis of breast tumours to the lung is the principal finding of a scientific team made up of two bodies from the University of Navarra, the Applied Medical Research Centre (CIMA) and the University Hospital of the University of Navarra.

Doctor Alfonso Calvo, researcher in the area of Oncology at the CIMA, led the work with the special collaboration of Doctor Ignacio Gil Bazo, cancer specialist from the University Hospital.

For this research, recently published in the scientific journal Oncogene, a transgenic mouse model which presented a greater tendency for developing metastasis was employed. The increase in what is known as the Vascular Endothelial Growth Factor (VEGF) in its mammary glands triggered profound changes in the tumoural structure, which enabled the malignant cells to leave the tumour and invade the lungs.

Finally, the pattern of genes responsible for this tumoural migration to the lungs was analysed and this was compared to that shown by women with breast tumours with pulmonary metastatic affectation. It was shown that five of these genes were common to the animal model and patients with breast cancer.

According to the results of this study, of the five genes identified, the Tenascina-C gene seems to be a good therapeutic target for the treatment of metastatic breast cancer. In fact, the blocking of the expression of this gene in the animal model enabled a significant reduction, both in tumour growth and in the incidence of pulmonary metastasis.

                                  
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