Mutations in Lettuce

There is and increasing demand for healthy foods that lower health risks and increase life span making lettuce which is commonly used in salads and sandwiches a very important vegetable and dietary staple in the western world. Lettuce was the second most consumed fresh vegetable per capita in the U.S. in 2008. Genetic mutation has and continues to play an important role in the evolution and improvement of lettuce. Mutations are occurring naturally and in the wild but at a very slow rate due to the inbred nature of lettuce. Resulting beneficial factors can be selected and exploited for human needs. There are several mutagenic agents such as x-rays and ultraviolet radiation that can be used to speed up mutation rates or produce mutants that do not occur naturally. The main purpose of creating these mutations is to achieve a desired goal, such as growing miniature lettuce heads or growing herbicide tolerant lettuce. The miniature lettuce mutation could potentially save an entire crop. Lettuce has a tendency to prematurely bolt, which is a rapid stem elongation, this rapid elongation of the stem will make a commercial lettuce crop worthless. These dwarf mutants were found to lack the gibberellic acid which is involved in regulation in stem elongation therefore they do not have this problem of premature bolting. Another major mutation on the world of lettuce and agriculture in general is herbicide tolerant plants. Weeds growing in leafy vegetables, such as lettuce, can lower crop yield and quality so it is essential to have them removed. The easiest way to remove these weeds would be with the application of a herbicide which would also kill the lettuce since it is a plant. So with an herbicide tolerant lettuce you can spray your fields with a general herbicide to kill the weeds and not have to worry about damaging your crop. Another mutation that has occurred in lettuce has lead to lettuce that is resistant to downy mildew. When having disease resistance plants you no longer have to worry about crop damage and loss due to disease and you also no longer have to worry about application of pesticides and all the hassles that accompany it.
This article interested me because it related with something I have a big interest in, which is plants and plant diseases, and related it to genetics by talking about mutating genes to create a desired crop or prevent disease.

Hunter Morris

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263626/?tool=pubmed

Genitopatellar Syndrome

In recent years there has been a rise in a new genetic disorder. The symptoms of the disorder are: an absence of a kneecap, a small scrotum, abnormal kidneys, facial defects, club feet, and mental retardation. A study was conducted on six boys and one girl of five different families. Two of the seven children were aborted with knowing their children had the syndrome. Three of the children did not survive but just a few years during adolescence and two of the children lived but suffered severe mental delay.

One of the main features from this condition is altered facial features. Those with the disorder often have a large, broad nose with a high nasal bridge. A small jaw bone is often noticed along with skewed facial features. The smaller jaw bone can be attributed to a smaller sized head.

There are numerous physical abnormalities that are displayed with the disorder. A common abnormality is the lack of a kneecap. Along with an altered knee, the children also suffered from club foot which occurs when the feet are not aligned with the body. Often times they are turned far inward until the feet would be nearly turned on their sides. One thing that can be easily noticed judging off physical attributes is that they often times have smaller hands than normal. Another physical defect is altered genitalia. In males the testicles can be shrunken to the point of little existence or the other defect is having either one or no testicles. For females, the clitoris is moved further to the front of the body and the labia or lips of the vagina are often enlarged.

The internal effects of genitopatellar syndrome vary but are often located with areas around the legs along with the physical deformity of the feet. As from the name of the disorder, those who are born with the condition are born without kneecaps. Yet the knee is not the only place for defects. Abnormalities to the hip bones can range in dislocation to proper orientation or flexion of the hips. If the children live old enough to ingest food, they often have troubles with swallowing. This disability can be attributed to hypotonia which is having low muscle tone or simply weaker muscles. Another internal effect is that of the kidneys. The children displayed dilated kidneys or are misshaped. Some of the kidneys from the patients also had cysts. Lastly, one symptom of the disorder is severe mental retardation. Of the two patients that lived beyond approximately one year, the retardation was severe enough to hinder them of independence and normal functioning.

The disorder is thought to be linked to chromosomes other than those that control sex and is recessively inherited. The parents of the children were examined to be healthy adults and did not interbreed within their family. The families were not related even though their children suffered the same effects. Genitopatellar syndrome is a crippling disorder than not only affects one physically but causes mental handicaps as well.

Cormier-Daire, Valérie. (2000). Genitopatellar syndrome: a new condition comprising absent patellae,

scrotal hypoplasia, renal anomalies, facial dysmorphism, and mental retardation. Journal

of Medical Genetics. Volume 37, Issue 7, 520-524.

Sara Puckett

Genetics of type 1 diabetes

Type 1 diabetes is a chronic disease in which there are high levels of sugar in the blood. While type 1 diabetes can occur at any age, it is most often diagnosed in children, adolescent, and young adults. Type 1 diabetes is a complex, multigenic disease. Nearly 40 years ago, the first reports of genetic association to type 1 diabetes were for the human leukocyte antigen region. Since then, researchers have not only been trying to pinpoint which alleles of human leukocyte antigen-encoding genes are responsible for type 1 diabetes association, but also which other genetic loci contribute to the type 1 diabetes risk. Human leukocyte antigen does not refer to a single genetic locus, but rather a region of the genome, containing less than 6543 unique allele sequences. There is also a strong association between type 1 diabetes and polymorphism in the promoter region of the insulin gene. Part of what makes sorting through human leukocyte antigen associations so difficult is the extremely large numbers of reported alleles at the human leukocyte genetic loci as well as differences in allele frequencies and haploid combinations among populations, incomplete penetrance of the human leukocyte antigen susceptibility loci, and epistatic interactions with other susceptibility factors. For some alleles of human leukocyte antigen, the risk of type 1 diabetes is determined by specific combinations of alleles, rather than by genotype. Multiple haplotypes are positively associated with type 1 diabetes, while many others are negatively associated. Specific genotypic combinations are also associated with increased risk, although still not the main cause. Maintaining a consistent nomenclature among scientists has been very challenging with the extreme polymorphism of the human leukocyte antigen-encoding loci. There has also been a dramatic increase in the number of reported human leukocyte alleles with new and better genotyping technologies, which adds to the challenges faced by modern scientists. There are dozens to thousands of alleles that exist for each human leukocyte antigen gene. In order to establish other genes in the human leukocyte antigen region as potential type 1 diabetes risk loci, scientists must first demonstrate an observed association in the human leukocyte region is a true disease susceptibility effect, and not only due to linkage disequilibrium. Currently, it is believed that type 1 diabetes results from an initial triggering event. This is followed by gradual autoimmune destruction of the pancreatic β cells, until the residual β cells are insufficient to meet the insulin demands of the body. Since the trigger of type 1 diabetes is unknown, the autoimmune process is usually undetected until the time of diagnosis. The rate of autoimmune destruction is unknown, and could vary among individuals. The end of the autoimmune process is marked by the destruction of pancreatic β cells by cytotoxic T cells. Even after almost forty years of research, human leukocyte antigen is still the strongest predictor of risk for type 1 diabetes, with reported odds ratios ranging from 0.02 to less than 11. However, the genetics of type 1 diabetes is more complex than any scientist could have predicted. Therefore, while scientists know quite a bit about the genetics of susceptibility to type 1 diabetes, more data is necessary to determine where the link is.

Works Cited:

Noble, Janelle A., and Henry A. Erlich. "Genetics of Type 1 Diabetes." PubMed Central. Cold Spring Harbor Perspectives in Medicine, Jan. 2012. Web. 13 Feb. 2012. .

Ashley Sisk

The Blue People of Troublesome Creek

Hematologist Madison Cawein, who traveled back and forth, from Lexington to Hazard, KY, explored rumors and legends of the blue people of the hills and hollows. He began his search at the local clinic and from there, explored all over the hills and creeks close by. The trait he searched for was the rumored blue people—no, not smurfs. These people were thought “to have a heart disease, lung disorder, or that simply their blood was closer to their skin.” After concluding that neither of these hypotheses were correct, Cawein did more investigation involving many blood tests. He originally suspected methemoglobinemia, a rare hereditary blood disorder that results in excess methemoglobin—a blue nonfunctional form or the red hemoglobin that carries oxygen to the body. Blue is the color of oxygen-depleted blood cells that you see in veins below the skin. Several causes of this could be abnormal hemoglobin formation, enzyme deficiency, or too much of a particular drug or vitamin. First, Cawein tested for abnormal or a deficiency of hemoglobin; the results were negative. He did some research that led to his new hypothesis of a diaphorase deficiency. Diaphorase is used by the body to break down methemoglobin into hemoglobin; if this is not present, methemoglobin numbers rise disproportionately in the blood giving it a blue tint. This doesn’t mean, however, that the individual is deprived of oxygen but strictly is a condition of pigment.

Cawein further explored the reason for this. He found it a recessive trait and is typically suffered from excessive inbreeding, or contiguous mating. The family tree he studied was that of Martin Fugate, an immigrant orphan from France. The pedigree that Martin made was extensive and displayed said inbreeding, which was common in the isolated area as there was few people in the area to begin with. Three families were mentioned: Fugates, Stacys, and Ritchies. It was only natural for a member of the family to marry “the girl next door” since choice was limited even if they had the same name…

To attempt to fix the embarrassing condition Cawein made 100 mg pills made of methylene blue which would hopefully reverse the blue effects, if only temporary. So the pill must be taken daily, as the methylene blue would be peed out. The study ended here. Cawein then focused on creating a pedigree, a chart displaying the family tree and a trait that is passed down. It is used to help trace back the origination of a gene, in this case Martin Fugate, the father of the Fugate clan, married Elizabeth Smith, a carrier of the trait. Martin was said to be blue thus passing the gene onto his seven children, four of which were blue. These children went on to pass the trait to the other two families as well as keep it in their own, marrying cousins. Once World Ward II rolled around the family began to spread out and marry others. Evidence of the blue gene would soon be lost to carriers of the trait and would be simply coincidence if they married another carrier unless they were distant family. Odds of that would be slim and highly unlikely.

This article interested me because I have family that live in Appalachia very close to Kentucky. I’ve heard stories about blue people but never really understood it or tried to do more research on it. I found it interesting because although the trait dispersed and the last remaining direct Fugate descendant died, the trait can still emerge. This trait was also found in Eskimos and Indians, which I also found very interesting.

By: Kara Ward

Cites:

• Cawein, Madison, Behlen, Charles H., Lappat, E. J., and Cohn, Jerome. Hereditary Diaphorase Deficiency and Methemoglobinemia. 1964. Archives of Internal Medicine. http://archinte.ama-assn.org/cgi/content/summary/113/4/578.
• Trost, Cathy. The Blue People of Troublesome Creek. 1982. Science Magazine, 82. http://www.indiana.edu/~oso/lessons/Blues/TheBlues.htm.
• http://topics.info.com/Who-were-the-Blue-People-in-Appalachia_171

Mutation Buffering

Each of us has come in contact with a person who has been taken captive by a harmful disease by no fault of their own but instead their adversity it at the hands of chance. We clearly see the detrimental effects mutations have on humans. Huntington’s disease and cystic fibrosis, for example, are familiar genetic diseases that affect humans in an array of severity. One person may have a mild case of cystic fibrosis whereas another individual suffers from the most severe case. Is this by chance? The research article, Trade-Offs and Environmentally Induced Mutation Buffering in Isogenic Caenorhabditis elegans, studied whether environmental stress changed the frequency of mutations’ harmful effects. Caenorhabditis elegans, abbreviated C. elegans, are nematodes or roundworms. The environmental stress levels of the organisms were increased by overexpressing the heat shock factor. The results of the environmental stimulus were that the harmful effects of mutations were lessened. For example, a generally lethal mutation, meaning deadly, among C. elegans resulted in a lethality rate of 17% that was normally 33%. Chaperone proteins were found to be a variable that affected the consequences of mutations. Environmentally induced stress resulted in the expression of chaperone proteins. Chaperone proteins are proteins that assist in the folding and unfolding of macromolecules. Chaperones decrease the likelihood of misfolding or the aggregation or grouping together of proteins. Therefore, temporary induced stress stimulus can promote mutation protection by increasing stress resistance.
The consequences of mutations vary individually. Hence, if a mutation is inherited, the affects the mutation will have on the individual depends on the chaperone levels within the individual and not the inherited mutation itself. The same holds true if chaperone levels were already higher in one individual than another without being induced, the individual with higher chaperone levels will have greater stress resistance. Chaperones were found to have a direct correlation with lifespan among C. elegans meaning, higher levels of chaperones resulted in a longer lifespan and the reverse also proved to be true.
Undoubtedly, all C. elegans could benefit from stress resistance in relation to susceptibility to mutations. However, stress resistance effects several other genes related to fitness. Fertility, for example is affected in that high stress resistance yields less offspring and low stress resistance yields more offspring. The organism C. elegans undergo diverse environmental conditions therefore their survival rate is increased by having both high and low stress resistance organisms within their environment. Misfortune
If the research conducted on round worms can be applied to human genetic diseases, then the importance of this study is clear. The ability to buffer the effects of mutations in humans would be a life changing discovery. Although the effects of mutations vary among individuals, the capacity to protect individuals from the consequences of mutations is predictable according to this study and its concepts may be applied to human genetics. This study was of interest to me because my healthiness is a mere grain of sand compared to the ocean of those suffering from the dire consequences of mutations. Any scientific step toward alleviating the effects of mutations is research worth reading, understanding, and applying.

Citation: M. O. Casanueva, A. Burga, B. Lehner, Science 335, 82 (2012); 10.1126/science.1213491.

Quanytta Johnson

Parkinson's Disease in the Amish Community

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting approximately 120 per 100,000 individuals in the United States. Parkinson’s disease is a disease that affects the way a person moves. It occurs when there is a problem with certain types of nerve cells within your brain. These certain nerve cells make a chemical called dopamine. Dopamine sends signals to the part of the brain that controls movement and allows the muscles to move smoothly and do what you want them to. However, with Parkinson’s disease, the nerve cells break down. Without these nerve cells, the body can no longer produce dopamine. Therefore, a person with Parkinson’s disease has trouble with their movement. Parkinson’s disease is progressive, which means it gets worse over time. This usually happens slowly over a long period of many years. There are four main symptoms of Parkinson’s disease. This includes tremors, stiff muscles, slow movement, and problems with balancing and walking. Tremors in the body are usually the first symptom of Parkinson’s disease. The cause of PD is unknown, although older age and smoking habit appear to be established risk factors.

The article I chose is called “A Genome-wide Scan in an Amish Pedigree with Parkinsonism.” The researchers of this study wanted to identify the PD genes in an eight generation Amish pedigree with apparent autosomal dominant Parkinsonism with incomplete penetrance. Autosomal dominance is a gene on one of the non-sex chromosomes that is always expressed, even if only one copy is present. However, since it has incomplete penetrance, it means that even if the individuals have the genes that would express Parkinson’s disease, not all would express it.

So far, seven genes have been identified in familial PD cases: α—synuclein (PARK1, PARK4), Parkin (PARK2), UCH-L1 (PARK5), PINK1 (PARK6), DJ-1 (PARK7), LRRK2 (PARK8), and ATP13A2 (PARK9).

Individuals who were being screened had to go through an interview with a board of genetic counselors. They were screened for a history of encephalitis, dopamine-blocking medication exposure within one year before diagnosis, symptoms of normal pressure hydrocephalus, or a clinical course with unusual features suggestive of atypical or secondary Parkinsonism. Participants were also evaluated for a history of exposure to substances known or suspected to cause Parkinsonism, including heavy metals or pesticides. Individuals with a positive symptom history of PD as well as unaffected individuals were personally examined by a board-certified neurologist with subspecialty training in movement disorders. Participants were classified as affected, unaffected or unclear, using published diagnostic criteria based on clinical history and neurologic examination.

Affected individuals had at least two cardinal signs of PD (tremors, slow movement, or rigidity) and no atypical features of Parkinsonism. Individuals with unclear status had only 1 sign of PD, a history of atypical clinical features, or both. Unaffected individuals had no signs of PD.

The severity of signs and symptoms was evaluated by the Unified Parkinson’s Disease Rating Scale. To figure out the genotypes of the individuals, DNA samples were prepared from whole blood using standard methods and stored using a bar-coded system. The genomic screen was conducted using a preselected set of 364 markers conducted in multiplex sets of two to three markers per sample.

What they found in this screening is that there were some genetic factors for why this pedigree has PD, but there is also evidence of environmental factors causing this disorder. This surprised the researchers because they believed with the inbreeding in this type of community; Parkinson’s disease would be from a result of genetic factors.

I thought this article is interesting because my husband is half Amish. Also, both my husband and his father are showing signs of Parkinson’s disease. It helped me better understand what exactly Parkinson’s disease is and where he could possibly be getting the disease from.

Citation: Lee, S., Murdock, D., McCaughley, J., Haines, J. (2008). A Genome-wide Scan in an Amish Pedigree with Parkinsonism. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764120/?tool=pubmed
Christina M. Strubhar

Genetics and Autism Spectrum Disorder

The article titled “Genetics and Mitochondrial Abnormalities in Autism Spectrum Disorders: A Review” gives a detailed overview of the research that has been done on genetics in relation to ASD or Autism Spectrum Disorder over the years. In this article autism is described by “The Diagnostic and Statistical Manual of Mental Disorders IV-Text Revised” as a complex neurobehavioral disorder characterized by deficiencies in social interaction, impaired communication skills and repetitive stereotypic behavior with onset prior to three years of age. In other words, people with ASD tend to have difficulty communicating and interacting with their peers and often enjoy repeating certain functions or behaviors. It must be made clear that ASD covers a very large range of severity from functioning ASD to very sever. Trying to find the cause of ASD or Autism Spectrum disorder is difficult and includes the role of the environment, the mitochondria and genes.

This article briefly looks into the role the environment plays in stating that family and environmental studies suggest that there are genetic risk factors present in ASD. Research suggests less than twenty percent of subjects with ASD can identify the cause of their disease to be linked to one gene or genetic factor. The rest of the subjects have many genetic causes and/or environmental factors that alter gene expression without changing the DNA sequence. This is referred to as epigenetic influences. Not only does the environment play a part in ASD but biological factors such as the mitochondria play a part as well.

The mitochondria play a large role in the cause of Autism Spectrum Disorder. The Mitochondria are cellular organelles and their function is to control energy production necessary for brain activity and development. Many studies have been done on the mitochondria and how it is linked with ASD and different types of result have been produced. For example, researchers Coleman and Blass proposed that mitochondrial energy production defects could cause abnormal brain metabolism in children with autism, leading to certain biochemical levels in the body to increase; these biochemical include lactate, pyruvate and alanine. Other researchers have found that many of their subjects with ASD often times had some sort of mitochondrial defect and even more researchers are finding mitochondrial abnormalities in young children with ASD. When learning about genetics and ASD we cannot only look at the mitochondria, we have to also look at how genes are a factor in causing Autism Spectrum Disorder.

There are certain nuclear genes that have been studies and correlations have been found between the defects of these genes and ASD. One nuclear gene that has been studied in particular is DNA polymerase gamma 1. Polymerase gamma 1 or POLG1 is an important enzyme in DNA processes; if there is any kind of mutation in this gene it will impact DNA replication as well as repair. Research has found that mutations of the POLG1 gene cause deletions of DNA genes. But what do these finding have to do with ASD? Autism Spectrum Disorder is linked to defects of a specific human chromosome region. The research mentioned before found a link between genes in the nucleus specifically on the chromosome region that ASD is found on. Therefor subjects with ASD were found to be more likely to have DNA over replication and/or deletions due to mitochondrial dysfunction.

To sum up, the environmental factors have to do with ASD but these factors are a bit more difficult to pin point and study. We know the role of the mitochondria and its defects have a relation to Autism Spectrum Disorder. Several studies have linked ASD to defects in the copying of DNA and interactions with nuclear genes. By looking at all three of these factors we hope to have a better understanding of what causes Autism Spectrum Disorder.

This article was very interesting to me and I really enjoyed writing about it. I decided to write about this article because I have a young cousin who has a form of Autism. I thought it would be interesting to learn what exactly caused him to get this disease. After reading the article I did learn a lot about what factors play a part in ASD. There is so much that goes into the causation of not only ASD but other diseases as well. I do not think I really understand how complex the human body is and how one tiny error can cause all kinds of problems, but this article helped me to see that.

cite: Dhillon S, Hellings J. A., Butler M. G. "Genetics and Mitochondrial Abnormalities in Autism Spectrum Disorder: A Review" 322-332 Current Genomics 2011, Vol. 12, No. 5

Posted By: M. Castaneda