Essay on Marfan Syndrome: The Case of Joey Jones

Aziz, N., Qin, Z., Bry, L., Driscoll, D. K., Funke, B., Gibson, J. S., & ... Voelkerding, K. V. (2015). College of American Pathologists' Laboratory Standards for Next-Generation Sequencing Clinical Tests. Archives Of Pathology & Laboratory Medicine, 139(4), 481-493 13p.

Genetic screening is done with RFLP analysis. RFLP stands for Restriction Fragment Length Polymorphism. RFLP analysis is used to find an identifiable pattern of fragments (an RFLP) that indicates a genetic marker. The genetic marker is unique and is inherited in all people with a disorder or disease. The RFLP comes from a strand of DNA near a suspected gene location that has been cut with a restriction enzyme into smaller pieces. The pieces of DNA are separated using gel electrophoresis into their distinctive bands. The RFLP is a distinctive pattern of the fragments in the gel. All people with the disorder or disease have the RFLP pattern, it is written in stone or in this case, DNA. DNA bands are studied to determine if a person has a disease, is a carrier, has no prior deposition to the disease, or if they will develop the disease in the future. A detailed human map is being developed by scientists worldwide who are contributing information to the human genome project. The human genome project is an attempt to map out every gene on every chromosome of the human genome. It is going slowly, but growth in knowledge of the genome is growing exponentially every year. Along with the growth, we are accumulating knowledge about more

40 mutations and 4 polymorphisms can be detected by the Tag-It 40+4 Luminex-based reagent system. There were two mutations that were removed from the 25 mutation original panel though; I148T and also 1078delT. There are 40 mutations that can be detected by this test, but two were removed because one of the mutations was decided to be a polymorphism and the other was too rare to test for.

Marfan’s syndrome is a rare hereditary disorder of the body’s connective tissue. The phenotypic traits include being tall, abnormally long stretched limbs and in the most severe cases the aorta can be prone to rupture and retinal detachment can occur [1]. Seventy five percent of cases for this multisystem disorder are genetic and inherited in an autosomal dominant fashion (a child can inherit it from just one parent): 25% are sporadic where neither parent has the syndrome [2]. Its prevalence is 1/5000 and of these affected individuals each has a 50% chance of passing on the mutated gene to their offspring [3]. Marfan’s syndrome is caused by mutations in the fibrillin-1 gene (FBN1) located on chromosome 15q21.1 [4]. Fibrillin is a large glycoprotein

It uses a simple blood sample from an expectant mother to analyze fragments of fetal DNA that are present in her bloodstream. These tiny pieces of fetal DNA are then sequenced in comparison with control DNA templates into whole genomes or targeted regions of chromosomes. The cffDNA test can be performed as early as the 10th week of gestation and produces meaningful molecular cytogenetic information. Until recently, this kind of information was retrievable only by more invasive procedures. The DNA sequencing test can also detect some aneuploidies that are not identified on standard screening. Studies show that the cffDNA test detects trisomy 21 with an accuracy rate of over 99% (Norton et al., 2015). This high level of accuracy is one of the main reasons why this technique should become the preferable screening

These tests include DNA-based methylation testing, fluorescence in situ hybridization, and genetic testing. The DNA-based methylation tests a specific region on chromosome 15 to find if there is any abnormal parent-specific imprinting. This means that the test will be able to determine if the chromosome is either inherited from the mother only or properly inherited from both parents (GHR 2014). For example, the deletion of the 5-6 Mb region of chromosome 15 would be what researchers looked for with the DNA-based methylation. However, the other tests are just as effective as the DNA-based methylation, because they are trying to get the same end result (Cassidy et al. 2012). The DNA-based methylation test would be able to show us that the 5-6 Mb region on chromosome 15 in deleted. Then from there people can look at what happens in the 5-6 Mb regions to determine that it causes several genes that help with providing instruction on making molecules to be lost. An example would be the nucleolar RNAs. This gene aids in regulating other RNA molecules, which help with producing proteins and other activities in cells (GHR 2014). Part of the segment that is lost on the paternal chromosome 15 also contains the OCA2 gene, which aids in determining the pigmentation of eyes, hair, and skin. While Prader-Willi syndrome is characterized by only having maternal chromosome 15, Angelman syndrome is characterized by only having paternal chromosome

The test uses gene sequencing technology to spot traces of DNA related to different cancers in screen blood samples. To be precise, it looks at 96 genetic markers associated with breast, ovarian, lung, colon and melanoma cancers - ones that have specific treatment regimens and are well known. Many cancer

This genetic material is known as deoxyribonucleic acid, or DNA. Different genes of those variations are known as alleles (Upadhyaya, 2017). Alternating forms usually result in the traits, either recessive, and dormant or dominant and visible. The primary technique used in this experiment is that of DNA fingerprinting and it uses the information stored in the alleles and genes to identify the individuals. DNA fingerprinting is the characterization of an individual’s genomes.

It has an introduction, methods, results and discussion section. The introduction talked about the different ways copy number variations can be detected. In the article, it mentioned whole-genome sequencing, genotyping arrays, exome sequencing. All of them have pros and cons, such as cost and being able to detect certain sizes of genes as being a method. In the methods section, the authors showed how they: controlled the quality of CNVs, filtered the genes, assessed the copy number quality in parent-child trios, defined gene- and exon-specific copy number calls, created genic copy number intolerance scores, stratified copy number variations by genic content affected, showed their predefined gene sets, and analyzed gene set enrichment. The main conclusions could be found in the results section of the paper, and the implications of the research findings could be found in the discussion

When utilizing PCR-RFLP, a DNA fragment is first amplified by PCR, then it is digested by a certain restriction endonuclease to generate a restriction polymorphic profile for the test subject species (Shaw et al., 2002). PCR amplification should be highly conserved among a species so that it can be easily amplified. Each fragment length is considered an allele, and RFLP occurs when the length of a detected fragment varies between individuals.

The computing component of sequences searching has increased the pace of the research as comparison of genetic

One of the newest of DNA testing methods is know as the Short Tandem Repeat method. What is it? Well, The human genome consists of fixed and repeated DNA sequences. The repeated sequences come in different lengths and are categorized by their corresponding length of the base repeating parts, meaning the amount of adjoining repeat units, and overall length of the repeat piece. The DNA regions with short repeat units, usually 2 to 6 bp units in length are known as Short Tandem Repeats or STR. STRs are found covering the inside of the chromosomal structure. STRs have numerous benefits that make them great for human identification.

Several screening techniques are used to determine the location of a disease causing gene therefore it is important for families to understand the process of genetic screening. All patients will be given a simple explanation on the process of inheritance and how 50% of each parent’s DNA is combined to make up the offspring’s DNA as well as an explanation as to why DNA segments are affected by mutations in genetic codes.

This breakthrough in genetic testing is not only helpful for parents to have unborn babies tested

A chromosomal genetic test technique analyzes the whole chromosomes or long lengths of DNA to verify if there are any large genetic changes, such as an extra copy of a chromosome that cause a genetic condition of concern to one’s health ( Scuffham & MacMillan, 2014). The biochemical genetic tests technique study’s the amount or activity levels of proteins; abnormalities in either may indicate changes to the DNA that result in a genetic disorder. Evidently, genetic testing can provide information about a person’s genes and chromosomes. The available types of genetic testing include: The newborn screening that is performed after birth to identify genetic disorders that can be treated early in life. In the United States (U.S), millions of expecting parents provide consent for their babies to be tested each year. Currently, almost all states test infants for phenylketonuria (PKU), a genetic disorder that causes intellectual disability and congenital hypothyroidism, a disorder of the thyroid gland if left untreated. Diagnostic type of genetic testing is done before or after birth to identify or rule out a specific genetic, chromosomal condition. In many cases, it is used to confirm a diagnosis in suspicious condition based on physical signs and symptoms (Scuffham & MacMillan, 2014).