MicroRNA and Gene Expression

Role of RNA in Gene Expression: What is MicroRNA?

Genes that code for proteins aren’t the only kind of gene. There are thousands that code for microRNA, which are fundamental to gene regulation and cell health.The Central Dogma of Molecular Biology: What Causes Gene Expression?

Since 1958, the central dogma of molecular biology has been: “DNA makes RNA; RNA makes proteins.” DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are made of long chains of nucleotides. Segments of DNA are transcribed into segments of RNA called messenger RNA (or mRNA). The mRNA is then translated into a chain of amino acids called a polypeptide, which is then folded into a three-dimensional structure, sometimes with other polypeptides, to make a protein. (Hemoglobin, the protein in red blood cells that carries oxygen molecules, has four of the same polypeptide folded together.) A gene, as defined by the central dogma, is a segment of DNA that codes for a protein. Each gene codes for one protein, and each protein is coded for by one gene. A gene whose protein is produced is a gene that has been expressed.

Gene Expression According to the Central Dogma

Proteins carry out the bulk of functions involved in running a living organism. Proteins control which other proteins are produced by causing or blocking transcription of their genes from DNA, or translation from mRNA. More copies of a protein can be produced faster if multiple copies of its mRNA are made. Different mRNA molecules also have different shelf lives – a few seconds to several days.

Often, opposing groups of proteins work in concert to determine the exact types and amounts of other proteins produced at any given time. The role of RNA in gene expression, meanwhile, is seen simply as an intermediary between DNA and protein synthesis.

A New Class of Gene

The Role of Micro RNA in Gene ExpressionOr so the understanding went until 2001 when the term “microRNA” was introduced into the scientific literature. It turns out that genes that code for proteins aren’t the only kind of gene.

Only about 2% of the human genome actually codes for proteins. Some of the other parts are important for things like regulating gene expression, or chromosome structure, but about 90% of it was formerly dismissed as “junk DNA” – obsolete genes, ancient inactive viruses, transposons and introns, and other portions with no apparent purpose. Some of it, however, turns out to code for microRNA.

MicroRNA (micro RNA, miRNA)

MicroRNA (or micro RNA, or miRNA) are segments of RNA that are transcribed from DNA in a way similar to messenger RNA. Some are found within introns (segments of mRNA that are removed after transcription, before translation). The key difference is their length – much shorter at only 21-23 nucleotides long, as opposed to about 2,000 for a typical mRNA – and they are not translated into proteins. Instead, they provide a mirror image match to portions of one or more mRNA molecules (that is, are complementary to them), with which they can pair-bind, thereby shutting down polypeptide translation and blocking production of the protein. In many cases, pair-binding also marks the mRNA for destruction.

In short, instead of producing a protein to oppose its matching mRNA’s protein, microRNA blocks mRNA directly, which removes a layer of complexity and allows for more precise timing in controlling gene expression.

The first microRNA was discovered in 1993, but their full significance wasn’t apparent until 2000, when a second one was found to be widespread throughout the animal kingdom. Thousands are now known, and they are involved in regulating gene expression in all aspects of running a living organism. Proteins still turn genes on and off, but microRNAs control how many proteins are made. Turning on a gene for one protein might also turn on a gene for a microRNA that stops production of a second protein. Moreover, many diseases have distinct patterns of microRNA gene expression. This makes them excellent for diagnosis, for future development of drugs that target them, and maybe even as future drugs themselves.

Resources and Images
Whitehead Institute for Biomedical Research – MicroRNA
Gene expression diagrams made by article author

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The Roles of Genetics and the Limbic System in Aggression

Important Roles of Genetics and the Limbic System in Aggressive Behaviors

There have been several studies that clearly demonstrate the role of genetics and the limbic system in aggression. Although the subject of aggression can be quite complex in human beings, this information will hopefully shed light on the limbic system genetics aggression relationship.Defining Aggression.

Aggression is quite easily defined in animals because of specific stereotyped patterns of violence including killing to mark a territory or to gain food. With humans, however, the definition of aggression can be more complex because of the complication of intent.

To better understand aggression, psychologists classify aggressive behaviors into one of the following three categories:
Predatory aggression – stalking and killing of other species.
Social aggression – this is the unprovoked form of aggression directed at another member of the same species. The purpose of such behavior is to establish dominance.
Defensive aggression – this behavior is set against threatening aggressors.

The Role of the Limbic System

Based on animal clinical trials, the different types of aggression are actually controlled by different subsets in the brain, specifically the limbic system. The limbic system is composed of several interconnected nuclei and cortical structures within the telencephalon and diencephalon. Although the system serves various functions, it is known for functions associated with self-preservation, endocrine, and autonomic functions. The limbic system plays a crucial role in emotional response, arousal, motivation and reinforcing behaviors. Because it is essential to survival, this system is closely connected to the olfactory system in most species of animals.

The main parts of the limbic system that are important in the study of aggression include the amygdala, limbic cortex, the septum, the pituitary gland and the hypothalamus.

Genetics and Aggressive Behaviors

The link between genetics and aggressive behaviors had been researched since the 1960s. The theory during that time was that men born with an extra Y chromosome will display violent tendencies. This was disproved due the rarity of individuals with an extra Y chromosome. It cannot explain the prevalence of aggression all over the world.

Despite the failure of the first attempt to correlate genetics to aggressive behavior, the scientific community believes that there is a genetic component behind aggressive behaviors. This is because violent behaviors have the tendency to run in families.

This can be best explained by determining the brain structures that have control over aggression. According to scientific facts, the amygdala is implicated as the key brain structure behind aggression. Based on the 1939 study of Kluver and Bucy, monkeys who had their temporal lobes removed were found to be very tame, yet manifested little fear. Modern studies later explained that such Kluver-Bucy syndrome can be attributed to the removal of amygdala. Modulation of the amygdala, on the other hand, increases aggression even in humans.

Hurdles for Further Research

Even with the finding that there is a possibility of inheriting a predisposition to violence, there remains hurdles for further research on this subject. The hurdle in studies is to separate the environmental factors from pure genetic influence. Furthermore, many psychologists argue that modeling aggression in the home, as performed for research purposes, is equivalent to promoting violence.

Scientists have been quite successful in identifying the role of limbic system genetics on aggression. Despite this knowledge, however, the genetic traits connected to aggression do not directly demonstrate pathological aggression. The scientists remain doubtful regarding the true factors that might contribute to this dangerous type of aggression within the society. This is the more important issue in resolving the problems in criminality and violence. Environmental factors such as exposure to television, internet, and other forms of influences are now being investigates as factors that may shape aggression. With the help of biologists, doctors, psychologist, and sociologists, we are slowly starting to understand the complexity of pathological aggression.

References
http://www.brainconnection.positscience.com/topics/?main=fa/aggression
http://www.dartmouth.edu/~rswenson/NeuroSci/chapter_9.html

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Understanding the Genetics of Achondroplastic Dwarfism

Genetics of Achondroplastic Dwarfism

In learning about the genetics of achondroplastic dwarfism we know that it is a very common type of dwarfism. This bone growth disorder is characterized by cartilage having trouble turning into bone. This is especially true for the long bones in the patients legs and arms. As the most common short-limbed dwarfism, it is seen in about one in 15,000 to 40,000 newborn babies.

Genetics

genetics of achondroplastic dwarfismIn understanding the genetics of achondroplastic dwarfism, we know that an FGFR3 gene mutation is the cause. This gene is necessary for the maintenance and development of brain and bone tissue. This condition is inherited in an autosomal dominant pattern. However, not every case is genetically inherited.

Signs and Symptoms

The characteristic appearance of this type of dwarfism is present at birth. Symptoms may include:

-Bowed legs
-Large head to body size is disproportionately different
-Shortened legs and arms
-Spinal stenosis
-Hands appear abnormal with persistent space between ring and long fingers
-Decreased muscle tone
-Prominent forehead
-Short stature
-Lordosis and kyphosis

Spinal stenosis is a condition in which the spinal column is narrowed putting pressure on the spinal cord.

Lordosis is a curving of the lower spine where it curves inward. Kyphosis is a curving of the midspine where it curves outward.

People with this condition can also have clubbed feet and hydrocephalus. Hydrocephalus is a buildup of fluid on the brain. This can lead to brain swelling and a variety of complications if not promptly treated.

Diagnosis

When a woman is pregnant, she can have a prenatal ultrasound. If this shows excessive amniotic fluid around her unborn infant, this condition is possible.

After the baby is born, an examination may show a front-to-back head size increase. The signs of hydrocephalus may be present. These may include irritability, sleepiness, eyes seem to gaze downward, seizures and vomiting.

In newborns, achondroplasia may be revealed in the long bones by X-rays.

Treatment

There is no set course of treatment for this condition. As the related abnormalities cause problems, they should be treated. People with hydrocephalus are treated by having their flow of CSF improved. This may be done by surgically removing the blockage or placing a shunt.

Spinal stenosis can often be managed with medications. If the patient is experiencing pain, nonsteroidal anti-inflammatory drugs can help to reduce it. Physical therapy and lifestyle changes can also be helpful. For acute episodes of increased pain, the patient may benefit from short-term stronger pain medications and/or steroid injections. Other medications the patient may benefit from include phenytoin, tricyclic antidepressants and carbamazepine. If the compression is severe, surgery may be necessary.

Lordosis and kyphosis are usually treated with the “wait and see” approach, where the condition is monitored until such time as treatment is necessary. Other issues will be treated if they arise.

Resources
Genetics Home Reference. (2006). Achondroplasia. Retrieved on April 14, 2011 from Genetics Home Reference: http://ghr.nlm.nih.gov/condition/achondroplasia
Cedars Sinai Medical Center. (2011). Achondroplastic Dwarfism. Retrieved on April 14, 2011 from Cedars Sinai Medical Center: http://www.cedars-sinai.edu/Patients/Health-Conditions/Achondroplastic-Dwarfism.aspx
Image Credits
DNA: svilen001 – sxc.hu

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What is the Science Behind “Genetic Babies”?

Genetic Babies and the Science behind altering genetics

Think designer babies are a thing out of a scary science fiction novel? Not only are we headed in the direction of altering the genetics of our offspring – to an extent – we already are performing similar feats.

Sex Selection

The concept of designer babies has been a subject of speculation in science fiction as well as a popular theme in ethical debates for decades. While most debates on the science behind genetic babies focus on should-or-shouldn’t issues, several technological barriers have already been overcome, allowing more and more people to instead focus on questions of how and when designer babies will come into actuality. The truth is, to some extent, they already exist.

One instance through which the goal of a designer baby has already been partly realized is sex selection, the technology for which has been around since the turn of the century. Genetic sex selection is done through a relatively simple process of sperm sorting, as it is the sperm that contributes either an X or a Y chromosome to a baby’s DNA, therefore making it the sex-determining gamete.

Y chromosomes contain slightly less DNA than X chromosomes – a fact which enables scientists to successfully distinguish sperm cells that tend to produce boys from those that tend to produce girls by staining the sperm’s DNA with a light-sensitive dye. This sex selection method is known as MicroSort. The chosen sperm is then either deposited directly into the uterus or used in the in vitro fertilization of eggs before implantation. In 2001, the Genetics and IVF Institute in Fairfax, Virginia reported a 90% success rate for girls and 73% for boys from Microsort gender selection.

Sex selection, a milestone in the science behind genetic babies, has proven to be particularly helpful to couples with a family history of X-linked diseases. Examples of these disorders, which almost always affect males, include hydrocephalus, hemophilia, Duchenne muscular dystrophy, and Fragile X syndrome.

Pre-Implantation Genetic Diagnosis (PGD)

PGD, another turn-of-the-century technology, is used to test embryos formed in vitro for genetic conditions prior to implantation in the uterus. PGD increases the chances of a successful pregnancy and reduces the risk of gene-related diseases in offspring. Of course, this technology produces designer babies only in the sense that their parents have the power of selection; however, 100% of the babies’ genes are still naturally inherited from the parents.

Two main methods are used in prescreening: polymerase chain reaction (PCR), which helps pinpoint monogenic disorders, and fluorescent in situ hybridization (FISH), which detects chromosomal abnormalities. One or two undifferentiated cells are commonly removed from the eight-cell embryos for testing. No genetic modification of the embryo is involved.

Today, PGD is used for strictly therapeutic purposes only; that is, it is only used to ensure that the babies produced do not have a genetic predisposition for disease. In 2009, a fertility clinic in Los Angeles offered PGD as a means of letting parents choose their babies’ hair and eye color. The program was soon shut down due to public outrage.

Future Possibilities

The science behind genetic babies doesn’t end there; other methods have been proposed which may someday, in theory, give rise to truly custom-designed babies. Human Germline Genetic Modification (HGGM) is one such method, wherein a change in the genetic makeup of the egg, sperm, or early human embryo would cause the baby to manifest certain genetic traits he can in turn pass on to his descendants. Another proposed method is Somatic Cell Nuclear Transfer (SCNT), which involves complete genome replacement and is therefore considered a form of cloning.

References
Women’s Bioethics
GM.Org
BBC
Time

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What is Protein Docking?

What Is Macromolecular Docking and What is Protein Docking? Why is it Important?

Macromolecular docking describes the way in which two very large molecules approach and interact with each other—in effect joining themselves—at least temporarily. Of prime importance in this maneuver is so-called “quaternary structure.” When the molecules are proteins, it is called protein docking.What is a Protein?

A proteins is a nitrogen-containing organic compound made from smaller compounds called amino acids. These amino acids are chosen from a total of some twenty varieties. They are a kind of natural polymer. The order in which the individual amino acids appear in a particular protein is called its sequence. As an example, collagen consists of the amino acids glycine (Gly), proline (Pro), hydroxyproline (Hyp), and hydroxylysine (Hyl).

Proteins constitute a sizeable percentage of the human body and are essential to many highly important life processes. They are closely associated with DNA, the chemical associated closely with heredity and genetic characteristics. However, proteins do much more. For instance, they are an important component of the “nuclear envelope” – the structure which isolates a cell’s nucleoplasm (contents within the nucleus) from its cytoplasm (contents of the cell in general). Collagen, mentioned above, is the main component of connective tissue in animals and in humans.

Myoglobin Protein by Aza TothMyoglobin Protein
PD by Aza Toth, Wikimedia Commons

What is Docking?

Docking between molecules may be likened to docking a ship at a wharf. Two molecules of protein unite at least temporarily to perform a specific function. How they do so depends upon a number of factors, one of which is steric—that is it is dependent upon available space and shape of the molecules involved in the docking process. Structure in a protein may be defined as primary, secondary, tertiary, and quaternary. What do each of these terms refer to? It is important to know to understand why it is particularly quaternary structure that is involved in protein docking.Molecular Structure: Primary, Secondary, Tertiary and Quaternary.

The primary structure of a protein refers to its sequence—what the order is of its constituent amino acids. Each of these component parts has a shape to it, influencing the total shape of the protein molecule.

Biological proteins may twist or take a shape with some measure of local regularity to it. Thus some proteins adopt a helical shape. Others exist as strands, and so forth. These shapes make up the secondary structure. Hydrogen-bonding plays a major role in secondary structure.

These helices and other shapes may in turn fold in various ways, giving rise to a globule, for instance. This degree of spatial behavior is termed tertiary structure.

A little more difficult to visualize is quaternary structure. This relates to the spatial arrangement of proteins that form into groups. Perhaps it could be likened, to outer space, which has not only its galaxies, but its galaxy clusters. It is this quaternary shape that is especially relevant in protein docking.

Molecular Modeling: DockingMolecular Modelin: Docking
Credit: LBNL/NERSC Visualization Group

Why Protein Docking is Important

Much as the principle of docking applies in the construction of a space station in outer space, docking enables the uniting of proteins into valuable functional cellular structures, whether they are to exist temporarily or permanently. This area of research is very modern and very complex. There are a number of sites online dedicated to those who are researching the property of protein docking as predicted by computer software. Scientists hope to learn much about the complexities of even the simplest of life’s building blocks, the single cell.

References and Resources
The University of Arizona – Campus Health Service: “What is Protein?”
The University of Utah: Discover How Proteins Function
Cornell University, Department of Molecular Biology and Genetics: Functions of Nuclear Envelope Proteins During Development
Florida State University – “A holistic approach to protein docking,” by Sanbo Qin and Huan-Xiang Zhou, Wiley Interscience, 2007

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What Causes Widow’s Peak Hair? Is Genetics Involved?

Is Genetics Responsible for a Widow’s Peak Hairline?

The rare “V” shape at the center of the hairline of some people is called “widow’s peak.” At eye level, it may be the first feature we notice. Some famous people have widow’s peaks. Is this phenomenon an indicator of personality, or only superstition? Does genetics play a role, as some suppose?

A widow’s peak is a downward “V” shape in the middle of the hairline. This term was originally used because this type of hairline was thought to indicate that a woman would outlive her husband. The shape reminded the observer of a style of headdress worn by a woman in mourning. Despite the name, both men and women can have a widow’s peak hairline.

Widow’s Peak and Genetics

There is debate as to whether a widow’s peak hairline is determined by genetics. For this reason, an article in OMIM by Johns Hopkins University says, “A pointed frontal hairline may be inherited as a dominant.” (Italics ours) But doubt is expressed by University of Delaware Professor John H. McDonald, of the Department of Biological Sciences. He refers to it as a “myth.”

If it is a genetically dominant trait, one parent possessing the trait should be able to impart the distinctive hairline, 50 to 100 percent of the time. This is because each parent has two genes for each heritable characteristic. So, if one parent has widow’s peak and the other one doesn’t, it is possible for at least 50 percent of the couple’s children to display widow’s peak. If the one parent possesses two genes bearing the characteristic, that percentage increases to 100.

If it is not a genetically dominant trait, what causes it? Since a number of prominent universities and other institutions accept the genetics explanation, a strong alternative theory has not surfaced. It is known, however, that certain genetic conditions incorporate the feature of a widow’s peak, such as Aarskog-Scott syndrome.

Widow’s Peak: Origin and Personality Traits

What is the etymology of widow’s peak? It dates back to at least the 16th century. Women in mourning would wear a peaked hood. It was felt that a woman with a hairline reminiscent of this hood would see her husband predecease her.

There is no evidence that widow’s peak contributes anything to personality. However, Hollywood begs to differ. A widow’s peak to them often reveals dark inner qualities, even evil tendencies. Consider, for example, Batman’s nemesis, the Joker. Or how about the movie villain—a serial killer—Hannibal Lecter? And who would fail to recognize the widow’s peak of Edward “Eddie” Wolfgang Munster of the television sitcom, “The Munsters?” Although he is also cute, Eddie is, after all, a werewolf! Then, too, there is Grandpa Munster—a vampire.

On the other hand (in real life) a V in the feminine hairline may be tolerated or even considered appealing. Some famous actresses with widow’s peak include Marilyn Monroe, Sandra Bullock, and Drew Barrymore.

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