Archive for the “Genetics” Category

The title stunned me as I was surfing the Yahoo News. At some evolutionary phase, birds really did have thumbs. So what happened to them? Researches at Yale University and the University of Wisconsin propose that it shifted its position after studies made on the gene expression in crocodiles, as published in PLoS ONE.

Going back now, birds have only three fingers, which until very recently where believed to be the 2nd, 3rd, and 4th respectively. The only problem this faced was that fingers in the early birds such as Archaeopteryx correspond to number 1, 2, and 3 “thumb, forefinger, and middle finger”. Fossil records clearly indicate that finger 4 and 5 “ring and pinky finger” were lost in the flying dinosaur ancestors of birds.

To end this debate, researchers began to focus on the expression of HoxD11 gene. In mice, digit 1 had no expression for this gene, which also held true for the 1st digit in birds, which suggests that in reality, it is actually a thumb. But to test this, it was compared to crocodiles, the closest living relatives to birds. The findings did in fact support what they suspected. The expression, as in mice, was absent only in finger one “the thumb”

So, birds at one time had thumbs. And the fact remains because they still do. It chose to develop at a different position in the body, that’s all.

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In a study conducted by researchers in the University of Maryland School of Medicine, physical activity has proved to counteract FTO gene “fat, mass, and obesity-associated gene” in a group of European descendants who resided in the USA, known as Old Order Amish.

FTO gene has recently been linked to obesity & increased BMI “Body Mass Index” in numerous studies. Europeans usually have one or two copies of a variation of this gene. The research has enforced this prior assumption but brought, yet, another advantage since the study was done on 704 men & women of similar descent and thus similar genetic makeup, which what makes them ideal for genetic research. This helped researchers study the effect of physical activity on the expression of this gene.

In subjects, who were physically active throughout their daily routine, having multiple copies of the FTO gene didn’t seem to affect their BMI, despite the fact that in those, who were less active, a link between their BMI and FTO gene was obvious. This suggests that the choices one has to make in everyday life can deeply impact our body’s response to its own genes.

In order to compare the different variations in this gene, subjects were asked to wear accelerometers to measure their body movement on a 24-hour basis for seven days. They were then classified accordingly in order to conduct a comparative analysis. The genetic analysis revealed that 26 SNPs in the FTO gene were linked to BMI.

In the future, this may help tailor methods to prevent obesity in genetically susceptible individuals. So, after all we can’t blame it on our genes. Our decisions might in fact make up who we are & who we will become.

Source: Medical News today

Original research paper: Physical Activity and the Association of Common FTO Gene Variants With Body Mass Index and Obesity. PMID: 18779467 (Vote for the abstract on Biowizard)

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As we learned in pharmacology, the drug upon reaching the site of action, it gives a certain response. However, what if that response varies among individuals in terms of potency, duration or even adverse effects. As an example, in 1950s it has been noticed that Caucasians show prolonged effects to suxamethoniun chloride where further investigations revealed that 1 in every 3500 Caucasians has a less efficient butyryltranseferase, that metabolizes suxamethonium chloride, thus showing prolonged half-life & slower recovery from surgical paralysis. This fact has led to the emergence of a very unfavourable term “especially to clinicians”, Idiosyncrasy, which means the abnormal response to drugs, food & toxic agents that is peculiar to an individual. However, understanding the basic underlying mechanisms that led to this variation, made the scientists realize that in this case,  the drug response is not only a matter of pharmacodynamic effects but is considered as a ring holding pharmacology at one side and the genetic make up (which is the DNA sequence of any protein dealing with the drug as receptors, carriers, metabolizing enzymes………, etc) at the other side. This understanding led the scientists to replace the old term of Idiosyncrasy with a better descriptive term known as pharmacogenetics.

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Variations in the genetic make up are diverse in types. The most common type is Single Nucleotide Polymorphisms (SNPs) which are single nucleotide substitutions that can be found in coding and non-coding regions in the DNA sequences of protein systems dealing with the drug. Another form of variation can be chromosomal aneuploidy as Trisomy, where an extra copy of a chromosome, carrying a gene coding for any protein system dealing with the drug, will in turn lead to response variation. As an example for that is in leukemic patients with down syndrome, since there is a third copy of chromosome 21 which bears Reduced folate Carrier gene that codes for the transmembrane Reduced Folate carrier system which is responsible for the of transport methotrexate inside the cell, thus having a third extra copy of this gene leads to the over expression of RFC & methotrexate toxicity due to high levels of intracellular methotrexate.                                

Now, with the fact that the genetic make up of an individual dictates the response has been laid down, the clinical application has become a consequent step. For example, regarding leukemic patients having down syndrome, as mentioned previously, they are highly predisposed to methotrexate toxicity & thus as a routine, these patients should be set on lower doses of methotrexate. This particular example is a little bit simple that is easily characterized by the well known phenotype of down syndrome patients. However, translating the basic knowledge of pharmacogenetics to useful clinical guidelines is a more complicated approach in terms of both characterizing the alteration in the genetic make up and the subsequent clinical decision regarding the choice of the drug, dose and the dosing schedule. For instance carrying out a SNP Genotyping for DNA sequencing and identification of SNPs is a difficult matter as SNPs are very scattered along the human genome, where it has been estimated that every 1,ooo base pair, one SNP is found. In addition, the functional characterization of this SNP on the protein level is a matter of complexity that requires well controlled studies (i.e. all other causes of response variation regarding the drug of interest are eliminated).

Inspite of the complexity of the investigations for clinical application, it is a productive promising approach that does have three positive impacts on the clinical application where upon the tailoring of the treatment protocol according to each patient genetic make up (individualized therapy), this will increase the efficiency of the medications, decrease side effects, adverse drug reactions, morbidities Image credit:& mortalities and thus reduce the finances of the clincal mangement of adverse drug reactions as well as toxicities that may be result from incompatibility of the drug with the genetic make up of the patient.


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Image Source: College of Agriculture & Natural resourcesIn an on-going study at the University of Rochester Medical Center, scientists have come across a new form of inheritance which would probably astonish Mendel himself. Research has shown that parents pass on the human herpes virus 6 “HHV-6” to their offspring because the virus has integrated itself into the infected parent’s chromosomes. And it is actually not as odd as it sounds. One in every 116 newborns is affected by this unique congential infection. The virus appears to integrate itself into a position in the chromosome concerned with the maintenance of the body’s normal immune function.

Typically, HHV-6 causes roseola which is characterized by high fever, rash, and mild gastrointestinal symptoms. However, the number of viruses found in children, who carry the virus within their genes, is much higher than those who were infected merely through the placenta. 86% of the children included in the study had the virus integrated within their chromosomes. The HHV-6 DNA itself was found in a hair sample provided by one of the parents. Only six of the congenitally infected babies were infected by the mother through the placenta.

The odd part about this does not lay in the fact that the virus has integrated itself within the chromosomes, but that it was actually passed on. So far, the long-term consequences on the children’s immune system is unknown but to have a virus lying around like that in their DNA…simply frightening, yet fascinating.

Source: Biology News Net

Press release: URMC website

Original research paper: Chromosomal integration of human herpesvirus 6 is the major mode of congenital human herpesvirus 6 infection. Pediatrics. 2008 Sep;122(3):513-20. PMID: 18762520. (Vote for the abstract on Biowizard)

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