TRMPL1 : The Role Of TRPML1

These strands are separated by length using electrophoresis and detected automatically by computers to be analyzed (Lyons, 2004). Another method of genetic testing is extracting one cell from an 8-cell embryo and using preimplantation genetic diagnosis (PDG) to determine the presence of disorder-causing genes (Holt, 2012).

(PCR), which isolates small fragments of DNA that have a high degree of variability from

The symptoms include bilateral, painless, subacute visual failure. The symptoms will not appear until the affected individual develops visual blurring in one eye. The central visual field will be affected in this eye, and 2-3 months later, these symptoms will become apparent in the other eye (Yu-Wai-Man et al., 2011a). There are 3 points at which a mutation in the mtDNA would almost certainly result in LHON. These are m.3460G>A, m.11778G>A and m.14484T>C. This information is known because over 95% of LHON pedigrees are known to harbour one of these mtDNA point mutations. (Yu-Wai-Man et al., 2009a)

Linkage testing is a type of indirect DNA testing used to narrow in on the location of a disease-causing gene within a family. It is typically used when the gene for a condition is undiscovered or when a family is thought to have a rare or unique mutation. Linkage can be used for diagnostic, carrier, and prenatal testing. (Genetics and Social Science, 2017).

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

Autosomal dominant LGMD occur less often than recessive dominant LGMD. In the metabolism myotilin gene mutations occur, it may be due to a deficiency of vitamin B12, vitamin E, folate or exposures to nitrous oxide. LGMD 1A disease normally occurs from the age 42 to 77, and develops in the same areas (hip, shoulder and back) however, it could spread to the leg muscles. Due to the fact that myotilin gene is mutated, it causes focal myofibrillar destruction to occur, and this results in intracytoplasmic deposits to float around in the blood stream. In one case study done in Barcelona in 2011, there were 13 patients who were all diagnosed with myotilin gene mutation disease. The results showed that the deposits of myofibrillar became immune to myotilin and cluster up the vacuoles and interfere with the Z-lines. Overall the study revealed that each patient shared the same phenotypic characteristics, LGMD 1A and myofibrillar myopathy variations which emphasizes that LGMD is a developing neuromuscular disorder (Montse,

The LMNA gene was first mapped using in situ hybridization. The gene was detected using clone LA-6, while the hybridization signals were detected using rhodamine-anti-digoxigenin. The samples were analyzed and photographed using a fluorescence microscope. Metaphase figures obtained from the photographs were observed to determine the amount of figures that probed for LMNA. The results showed that 90% of the metaphase figures probed for lamin A/C (Wydner et al. 1996). After analyzing the bands, LMNA was localized to chromosome 1q21.3, giving the chromosomal position of the LMNA gene.

Med. Genet 2009. 46, 825–833; Cardoso, C., Leventer, R.J., Ward, H.L., Toyo-Oka, K., Chung, J., Gross, A., Martin, C.L., Allanson, J., Pilz, D.T., Olney, A.H., et al. (2003). Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3. Am. J. Hum. Genet. 72, 918–930). MDS is caused by a heterozygous deletion of chromosome 17p13.3, involving several genes including PAFH1B1 and YWHAE coding for LIS1 and 14-3-3 proteins, respectively. This deletion induces malformations during cortical development (Dobyns, W.B., Stratton, R.F., Parke, J.T., Greenberg, F., Nussbaum, R.L., and Ledbetter, D.H. (1983). Miller-Dieker syndrome: Lissencephaly and monosomy 17p. J. Pedod. 102, 552–558; Chong, S.S., Pack, S.D., Roschke, A.V., Tanigami, A., Carrozzo, R., Smith, A.C.M., Dobyns, W.B., and Ledbetter, D.H. (1997). A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3. Hum.

Deletion/duplication analysis – This test detects exonic and whole gene deletions. The mutation detection frequency for this test is unknown.

They are involved because the LMNA gene produces several slightly different proteins called laminas, of the major ones being Lamin A (also known as progerin) and Lamin C. These proteins are generally made throughout the whole body’s cells. The disease is causes the LMNA gene which to become mutated. Althought, this does not causes any harm to lamin c protein, it causes the lamin A protein to misshape, by missing out on 50 amino acids near one end. This is bad because the lamin A protein is a component the nuclear cell membrane. This misshaped version of lamin A is which is responsible for the disorder; it makes it so that it cannot be processed properly in a cell, which then causes a disrupted shape in the nuclear envelope. All in this mutation damages a cell’s structure and function to a nucleus which in turn causes the cells to die

are pore forming proteins which allow the passage of ions that are charged into and out of the cell

ii. Another type of testing is called Chorionic villus sampling. The doctor takes a sample of placenta and once again tests it for a mutation in FMR1.

Apart from this, Marfan syndrome has several symptoms. However, the most prominent indicators affect the skeletal, cardiac, and optical systems. The entire fibrous connective can also be affected (4). Other signs include extreme nearsightedness, an abnormally curved spine, flat feet, excessively limbs, and extraordinary and overcrowded teeth. The central cause of the condition is a deficiency in the gene that enables the human body to produce the fibrillin protein, which provides the connective tissue the strength and power to support the body organ (4). Along with this, an individual inherits the abnormal from parents who had the disorder, and the condition can occur in men and women in all races as well as

The LMNA gene is a member of the intermediate filaments type V, lamins. It is placed at chromosome 1, position 22. The LMNA gene codes for two proteins, lamin A and lamin B. These two protein are similar in amino acid sequences, but a slight difference make lamin A longer than lamin C. These proteins main function is to support the shape of the nuclear lamina (envelope), the fibrous structure surrounding the nucleus. The nuclear membrane regulates the the exchange of molecules through the nucleus. Scientist also believe that the nuclear lamina regulates the expression of certain genes(LMNA, 2013). When the LMNA gene is damaged due to mutations it can produce altered lamins. These lamins can disrupt the shape of the nuclear lamina. With a distorted nuclear lamina the development of the peripheral nervous system and skeletal muscle system is interrupted. It can also prevent fat infiltration of muscle and bone marrow depending on the type of mutation that occurred in the LMNA gene (P02545 - LMNA_HUMAN, n.d).

The polymerase chain reaction or PCR for short can be used to create many copies of DNA. This allows the DNA to then be visualized using a dye like ethidium bromide after gel electrophoresis. The process has been refined over the years, however the basic steps are similar.