December 11, 2006

How much of human height is genetic and how much is due to nutrition?

Molecular biologist Chao-Qiang Lai of the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University answers.

This question can be rephrased as: "How much variation (difference between individuals) in height is attributable to genetic effects and how much to nutritional effects?" The short answer to this question is that about 60 to 80 percent of the difference in height between individuals is determined by genetic factors, whereas 20 to 40 percent can be attributed to environmental effects, mainly nutrition. This answer is based on estimates of the "heritability" of human height: the proportion of the total variation in height due to genetic factors.

Human height is a quantitative, or metric, trait, i.e., a characteristic that is measured in quantity, and is controlled by multiple genes and environmental factors. Many studies have estimated the heritability of human height. Often, these studies determine heritability by estimating the degree of resemblance between relatives. One can separate genetic effect from environmental effects by correlating genetic similarity between relatives (twin, siblings, parents and offspring) with their similarity in height. To accurately measure how genetically similar relatives are, one can measure the number of genetic markers they share. For example, Peter M. Visscher of the Queensland Institute of Medical Research in Australia recently reported that the heritability of height is 80 percent, based on 3,375 pairs of Australian twins and siblings. This estimate is considered to be unbiased, as it was based on a large population of twins and siblings and a broad survey of genetic markers. In the U.S., the heritability of height was estimated as 80 percent for white men. These estimates are well supported by another study of 8,798 pairs of Finnish twins, in which the heritability was 78 percent for men and 75 percent for women. Other studies have shown height heritability among whites to be even higher than 80 percent.

Because different ethnic populations have different genetic backgrounds and live in different environments, however, height heritability can vary from one population to another, and even from men to women. In Asian populations, the heritability of height is much lower than 80 percent. For example, in 2004 Miao-Xin Li of human Normal University in China and his colleagues estimated a height heritability of 65 percent, based on a Chinese population of 385 families. In African populations, height heritability is also lower: 65 percent for the population of western Africa, according to a 1978 study by D. F. Roberts, then at Newcastle University in England, and colleagues. Such diversities in heritability are mainly due to the different genetic background of ethnic groups and the distinct environments (climates, dietary habits and lifestyle) they experience.

Heritability allows us to examine how genetics directly impact an individual's height. For example, a population of white men has a heritability of 80 percent and an average height of 178 centimeters (roughly five feet, 10 inches). If we meet a white man in the street who is 183 cm (six feet) tall, the heritability tells us what fraction of his extra height is caused by genetic variants and what fraction is due to his environment (dietary habit and lifestyle). The man is five centimeters taller than the average. Thus, 80 percent of the extra five centimeters, or four centimeters, is due to genetic variants, whereas one centimeter is due to environmental effects, such as nutrition.

Heritability can also be used to predict an individual's height if the parents' heights are known. For example, say a man 175 cm tall marries a woman 165 cm tall, and both are from a Chinese population with a population mean of 170 cm for men and 160 cm for women. We can predict the height of their children, assuming the heritability is 65 percent for men and 60 percent for women in this population. For a son, the expected height difference from the population mean is: 0.65 x [(175 - 170) + (165 - 160)] / 2, which equals 3.25 cm; for a daughter, the difference is 0.6 x [(175 - 170) + (165 - 160)] / 2, which equals 3 cm. Thus, the expected height of a son is 170 + 3.2, or 173.2 cm, and of a daughter 160 + 3, or 163 cm. On the other hand, environmental effects can add 1.75 cm to a son's height: 0.35 x [(175 - 170) + (165 - 160)] / 2, and 2 cm to a daughter's: 0.4 x [(175 - 170) + (165 - 160)] / 2. Of course, these predictions only reflect the mean expected height for each of the two siblings (brothers and sisters); the actual observed height may be different.

Discovery of new gene gives hope to ALS sufferers

A recent discovery by a consortium of researchers, has given hope to individuals with amyotrophic lateral sclerosis (ALS), aka Lou Gehrig's disease. Headed by professors at the University of Massachusetts’ Medical School, the breakthrough relates to the discovery of the KIFAP3 gene variant, which substantially improves survival of individuals with the disease.

Reported in the Proceedings of the National Academy of Sciences the discovery of the KIFAP3 gene is an important and vital step in the understanding and possible future treatment of the disease. The Gene itself has been identified by the researches as being a genetic factor that determines the rate of progression in individuals with ALS; it represents the first of the only four known genes associated with causing familial ALS that has been linked to this rate of progression.

The discovery and isolation of the KIFAP3 gene was as a result of an international collaboration between more than 20 research teams from the U.S., Mexico, Israel and Europe that studied around 1800 people with ALS and 2200 unaffected controls. The researchers were looking for a naturally occurring gene variation that would influence a person’s susceptibility and the way that the disease manifested itself over time. This led the researches to the KIFAP3 gene, which was found to increase a person’s survival time by 40 – 50%. Due to the only recent discovery of this gene, researchers have yet to isolate specifically the way in which the gene variant affects the progression of ALS, however they know that its in involved with many cellular processes most specifically the transport of molecules within the nerve cells.

The hope in this discovery is that with further study not only can this gene lead to a better understanding of the progression of the condition itself but that it will also allow development of new treatments to combat the disease. Whereby treatments can be tailored to target and exploit the benefits of this gene variant. Especially as the collaboration showed that the variant by itself was comparable in effectiveness to the only available drug in the US, Riluzole.

ALS is a ‘progressive, neurodegenerative disorder affecting the motor neurons in the central nervous system. As motor neurons die, the brain's ability to send signals to the body's muscles is compromised. This leads to loss of voluntary muscle movement, paralysis and eventually death from respiratory failure’ it has no definitive cause and no cure - http://www.medicalnewstoday.com/articles/149766.php


References –

- http://www.medicalnewstoday.com/articles/149766.php
- Proceedings of the National Academy of Sciences

Mammalian Genomes

The mouse genome was the second mammalian genome sequence completed after the human genome. Approximately 4/5ths of genes they share in common, and studying these common genes in mice is of importance in treating human disease. This new research has effectivaley identified the remaining 1/5th of genes occuring in mice only, yielding information on how mammalian biologys differ from a genetic context.

"In retrospect, our previous picture of the mouse genome was incomplete. Only when all the missing pieces of the genomic puzzle had been filled in did we realize that we had been missing large numbers of genes found only in mice, and not in humans," says Dr. Leo Goodstadt from the MRC Functional Genomics Unit.

The new research allows conserved sequences to be overlayed between mice and humans, leaving the remaining genes in each genome species specific. Thus is of importance in evolutionary genetics. By comparing more distantly phylogenetically related organisms genomes, highly conserved genes can be identified, while genes specific to various taxa of life can also be attributed to the resultant diversity.

http://www.sciencedaily.com/releases/2009/05/090526202722.htm

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Genes links heart and gum disease

Gum disease has been genetically linked to cancer, although the German researchers who discovered the link are not exactly sure how. Periodontitis (gum disease) and Coronary Heart Disease (CHD) have the same risk factors, most importantly; smoking, diabetes and obesity. Researchers have found similarities between the bacteria found in the oral cavity and in the coronary plaque which both have an imbalance immune reaction and chronic inflammation.

A theory that researcher have come up with is that the bacteria in the oral cavity trigger a low grade inflammatory response throughout the body, which prompts strokes and heart attacks in the arteries.

The gene linking the two conditions is said to be found on chromosome 9. In the latest study the gene linking the two diseases has been found both in a group of 1097 patients diagnosed with heart disease and in 151 patients with aggressive Periodontitis. It is known which protein the gene encodes, however it is not yet clear as to how they are linked to the two conditions.

Full Article: http://news.bbc.co.uk/1/hi/health/8063512.stm

Elliot Beath - 42006570

Arthritis Drug Might Prove Effective In Fighting The Flu

At the present time, the treatment for the Influenza A virus is an antiviral drug known as Tamiflu, which prevents the virus from spreading within the body of a person, but only if it is taken with the first 48 hours of symptoms manifesting.

Researchers have recently found that a drug for treating rheumatoid arthritis has been effective in reducing the affects of the Influenza A virus. They found that mice that were infected with Influenza A had a positive response to the drug known as Abatacept which is commonly used for rheumatoid arthritis. The findings show that by tempering the response that influenza has on the immune system may alleviate some of the more severe symptoms and even reduce mortality from this virus. Mice were injected with white blood cells (memory T-cells) which had been primed to fend off the virus, due to previous exposure to Influenza A. They found that the mice which had been injected were less likely to become as sick and therefore recovered much faster with minimal damage to the lungs in comparison to the mice without the injection. "Moreover, treatment with Abatacept significantly improved survival for mice infected with a lethal dose of influenza virus," Dr. Farber says. "The survival rate for the treated mice was 80 percent, compared to 50 percent for the mice that weren't treated."

Researchers are currently testing Abatacept on healthy mice which have not been exposed to the virus to see how well they respond to the drug in a controlled environment. Instead of having “memory T-cells” these mice have “naïve t- cells”, which means they have not previously been exposed to influenza. The outcome of these tests will determine what happens in the long term.

Link: http://www.sciencedaily.com/releases/2009/05/090526114803.htm

Opposites attract: How genetics influences humans to choose their partners

When it comes to choosing a mate, opposites really do attract, according to a Brazilian study that found people are subconsciously more likely to choose a partner whose genetic make-up is different to their own. They found evidence that married couples are more likely to have genetic differences in a DNA region governing the immune system than were randomly matched pairs.

Scientists said it was not clear what signals attract the body to people who are genetically dissimilar to themselves, but suggested body odor or even face structure could play a role.
Many researchers have found evidence than animals are attracted to members of the opposite sex with differences in major histocompatibility complex or MHC, an immune system factor that also plays a role in having healthy offspring.The MHC is a large genetic region situated on chromosome 6, and found in most vertebrates. It plays an important role in the immune system and also in reproductive success. Apart from being a large region, it is also an extraordinarily diverse one.

The team compared genetic data from 90 married couples with data from 152 randomly generated control couples. They found the real couples had significantly more dissimilarities in MHC.

"Parents with dissimilar (genetic regions) could provide their offspring with a better chance to ward infections off because their immune system genes are more diverse," they wrote in a summary preparation.

Previous studies have suggested animals may use body odor as a guide to identify possible mates as being genetically similar or dissimilar, she added, but other physical factors may also be involved.

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Link: http://www.sciencedaily.com/releases/2009/05/090525105435.htm

Tackling the diagnosis of limb-girdle muscular dystrophy 2A

Autosomal recessive limb-girdle muscular dystrophies (LGMD) cause the progressive wasting of proximal limb-girdle muscles. These are a group of disorders that include at least 14 different genetic forms, the most common of which are LGMD2I found many in Northern Europe and LGMD2A also widespread in many European countries, Japan, Russia and Australia (Fanin et al. 2009). The LGMD2A type of the disorder is caused by mutations of the CAPN3 gene which encodes for a muscle-specific proteolytic enzyme called calpain-3. This enzyme plays a roll in the process of sarcomere (basic unit of muscle filaments) remodelling.
Due to its high frequency there is an increasing demand for the molecular diagnosis of LGMD2A. The current way this is done is via mutational analysis of the gene. But this is a cumbersome task as CAPN3 is a large gene. To improve this process Marina Fanin, Anna Nascimbeni, Elisabetta Tasca and Corrado Angelini designed a new approach. Their diagnosis of LGMD2A was biased on a preliminary quantitative protein analysis of calpain-3 from a muscle biopsy to identify patients with abnormal levels due to the mutations in the CAPN3 gene. This was combined with this was an analysis of calpain-3 autolytic activity when levels were found to be normal. A mutation screening of the CAPN3 gene by single strand conformational polymorphism was then used as a final tool to identify patients who showed normal levels and autolytic activity of the calpain-3 enzyme but still my have LGMD2A due to mutations of the CAPN3 gene and to confirm the findings of the first 2 tests.
Fanin et al. study found protein defect in 87 of 519 patients. A further 108 patients who showed normal calpain-3 levels and LGMD phenotypes had the analysis of calpain-3 autolytic activity levels which identified a further 17 cases with loss of autolytic function. The mutations screening was conducted on 282 patients which included the 87 with protein deficiencies, the 17 patients with loss of autolytic function and another 178 patients with normal protein levels but with LGMD phenotypes. They identified 66 different mutations of the CAPN3 gene including 6 new mutations that had not been previously reported. Mutations were found in 80% of cases with calpain-3 defects and in 88% of cases displaying the loss of the enzymes autolytic function. A further 10 patients, with normal calpain-3 and autolytic function levels but with LGMD phenotypes, were identified via the mutation screening.
This research shows that the more cost affective methods of calpain-3 analysis combined with autolytic activity analysis may be used to initially identify patients likely to have LGMD2A. Also the uses of autolytic function analysis enable the ability to identify patients with mutations that render the calpain-3 protein inactive but still produce it in normal level. This would allow larger scale testing of patients prior to the cumbersome process of mutation screening.

Reference:
Fanin, M., Nascimbeni, A.C., Tasca, E. and Angelini, C. (2009) How to tackle the diagnosis of limb-girdle musclar dystrophy 2A. European journal of Human Genetics. 17, p598-603.

Full article at: http://www.nature.com.ezproxy.library.uq.edu.au/ejhg/journal/v17/n5/pdf/ejhg2008193a.pdf