SPTLC1 Genetic Analysis

Decent Essays
Over the first five months of my M/Phill program I worked on two major projects: SPTLC1 and UNC13a genes.

SPTLC1 Project

The goal of SPTLC1 project was to show that mutations in SPTLC1 gene are the cause of amyotrophic lateral sclerosis(ALS). The following project was done in three steps: exome sequencing of a trio, exome sequencing of a large ALS cohort and matched control samples, and Sanger sequencing of SPTLC1 gene. The projects began with the discovery of a family that consisted of unaffected parents, one severely affected by ALS child and an unaffected sibling. Our group exome sequenced DNA from each member of this family. Exome data analysis led to the discovery of de novo mutations in the affected child but not in the parents or sibling suggesting that the discovered mutations could be the cause of ALS. To further examine SPTLC1 gene, our group exome sequenced a large number of ALS cases and controls. Analysis of the
…show more content…
Looking at the structure of the UNC13a gene we observed that it is rich in short repeats. Based on this observation we hypothesized the hit detected during GWAS analysis could be due to an expansion of one or more of these repeats.
To determine if there is a repeat expansion on UNC13a gene I selected 26 previously reported short repeats on UNC13a gene and tested each one on 86 sporadic and 10 familial ALS samples using the following three methods: repeat-primed PCR, fluorescent PCR, and Sanger sequencing. I chose repeat-primed (RT-PCR) because it is a robust method to detect repeat expansions. Fluorescent PCR helps to determine if both alleles are amplified by PCR. Finally, Sanger sequencing helps to determine sample heterozygosity, to look for monoallilic amplification and for sample drop-outs due to an expanded allele.

Related Documents

  • Great Essays

    Stem Cell Assignment 1. Summary of “Your Inner Healers” New scientific discoveries have shown that adult mouse cells can be “rewound” to once again be pluripotent like they were in their former embryonic state by adding a mixture of genes to the cells (called induced Pluripotent Stem Cells, or iPSCs). This contradicts the natural progression of cells’ potency as they age: in their early formation, embryonic cells have the ability to mature into any one of the 220 types of human cells, and soon after that they begin to lose potency and are only multipotent — able to develop into just a few different types of cells, until finally they become terminally differentiated, and therefore unable to develop into any other types of cells.…

    • 1720 Words
    • 7 Pages
    Great Essays
  • Superior Essays

    Lou Gehrig Biography Essay

    • 1561 Words
    • 7 Pages

    Ninety to ninety-five percent of people diagnosed have sporadic ALS, which is the most common form. A person could have no history of health issues, and could still get sporadic ALS. The leftover five to ten percent of cases is Familial, which is inherited by family members. For those who have Familial, a fifty percent chance of passing it to offspring is at risk. Jean-Martin Charcot, French neurologist, discovered this disease in 1869 (“What is ALS?”).…

    • 1561 Words
    • 7 Pages
    Superior Essays
  • Great Essays

    Fruit Fly Lab Report

    • 1571 Words
    • 7 Pages

    Name: Alexis Vick Drawer/Group #: 12 PS ID #: 1059363 Three digit mutant code: 458 BIOL 3311 Fall 2014 Lab Section: 20091/Tu4 Date: 09/29/14 TA Instructor Name: Laura Montier Drosophila Melanogaster: Decapentaplegic gene The fruit fly, Drosophila Melanogaster, has been used for years as a model for genetics.…

    • 1571 Words
    • 7 Pages
    Great Essays
  • Improved Essays

    Amyotrophic Lateral Sclerosis also known as, ALS or Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Breaking down the disease into Greek language “A” means no, “Myo” refers to one’s muscles, and “Trophic means no nourishment to the muscles. Lateral identifies the part of the person’s spinal cord where the nerve cells that report to and control muscles are located and Sclerosis means scarring. These translations give people a better understanding of what ALS affects. ALS affects the motor neurons in the spinal cord and brain which means that Amyotrophic Lateral Sclerosis affects the neuromuscular system of the body.…

    • 1809 Words
    • 8 Pages
    Improved Essays
  • Great Essays

    There have been concentrated cases in football players, both American and European kind of United States players, Italian players, and English players. Scientists believe that ALS is caused by a combination of external and genetic factors, but external factors have not yet been…

    • 1511 Words
    • 7 Pages
    Great Essays
  • Improved Essays

    Living with ALS is difficult to live with, but thanks to the help and support foundations offer it makes it easier for a person to continue their life; despite of knowing that the chances of recovery is…

    • 1330 Words
    • 6 Pages
    Improved Essays
  • Improved Essays

    Amyotrophic lateral sclerosis (ALS) Within this defined disease with its specific symptoms, the cause of ALS could potentially be glutamate but it is still unknown if that's a primary…

    • 620 Words
    • 3 Pages
    Improved Essays
  • Improved Essays

    Cte Crisis In Sports

    • 1144 Words
    • 5 Pages

    CTE Crisis Today, people begin to question sports regulations due to a massive discovery of Chronic Traumatic Encephalopathy and Amyotrophic Lateral Sclerosis being found in the majority of athletes. As a whole, people are not seeing the true effects of athletes are struggling through. When one football game is over, fans continue into the next week and expect the same CTE-ridden athletes to endanger their life. However, this has been a national crisis we all have been blinded to for years. Changing the regulations of the game for the greater good is necessary and needs to happen quickly.…

    • 1144 Words
    • 5 Pages
    Improved Essays
  • Improved Essays

    Tay Sachs Disease is a genetic disorder where the nerve cells in the brain and spinal cords are destroyed. Although anyone can carry this genetic mutation, it is most common of people with Ashkenazi Jewish background. Approximately 1 in every 27 of their population carries the gene for Tay Sachs. The gene mutation that can cause Tay Sachs is the HEXA gene. The chromosome that contains the gene is chromosome 15.…

    • 577 Words
    • 3 Pages
    Improved Essays
  • Improved Essays

    Multiple Sclerosis and the EAE model Background: Multiple sclerosis is a chronic inflammatory disease that affects the CNS (brain and spinal cord). MS attacks the myelinated axons in the CNS, causing adverse effects in motor and autonomic function. The four major categories of MS are relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive-relapsing MS but the course of the disease remains very unpredictable. Although tests to diagnose MS do not exist, studies have shown that genetic and environmental factors may have a substantial effect in the incidence of MS. For example, the incidence rate of MS is twice as high for women compared to men and significantly higher in people with a Northern European.…

    • 753 Words
    • 4 Pages
    Improved Essays
  • Decent Essays

    Alignment was performed with tophat v2.0.6 (http://tophat.cbcb.umd.edu). Alignments were processed using SAMtools v0.1.2, which generates site-specific allele frequencies using overlapping reads (read pileup). Allele specific expression was quantified by determining whether or not each overlapping read at mutant site matched the reference or the alternative allele. These summed counts represented our measures of relative allelic abundance at that site. Any deviation from equal allelic abundance was reflected allelic imbalance.…

    • 69 Words
    • 1 Pages
    Decent Essays
  • Superior Essays

    Autism spectrum disorder (ASD) is a developmental disorder that affects the brain’s development of social and communication skills. A person with autism may have repetitive behaviors, social challenges, and communication difficulties which last throughout a person’s lifetime. About one percent of the world’s population is living with autism, and about 3.5 million Americans are living with an ASD. There is no known single cause for autism, but most accept that autism is caused by abnormalities in brain structure or function. Brain scans show differences in the brain structure when compared to a neurotypical brain (Autism-Society).…

    • 1752 Words
    • 8 Pages
    Superior Essays
  • Improved Essays

    Multiple sclerosis is a neurological disease, and a chronic condition, which means it progressively gets worse overtime. There is a substance called myelin that wraps around your nerves to protect them, but MS breaks down that substance, and your body attacks itself. The unprotected nerves can't function as they would with normal healthy myelin. The damaged nerves produce many symptoms. Some symptoms include; trouble walking, feeling tired, muscle weakness, blurred vision, numbness and tingling.…

    • 612 Words
    • 3 Pages
    Improved Essays
  • Superior Essays

    ALS is an incurable and fatal disease that causes gradual muscle weakness and paralysis that begins between the ages of 40 and 70, and leaves its victims with 2 to 5 years to live. (Nettina, 2014) According to Nettina (2014), the cause of ALS is unknown, but what is known, is that ALS, “Results in progressive loss of voluntary muscle contraction and functional capacity, involving the legs, feet, arms, and hands, and those that control swallowing and breathing.” Although ALS debilitates the body, it does not harm the…

    • 2293 Words
    • 10 Pages
    Superior Essays
  • Improved Essays

    I was keenly aware of the importance of Genetics in health care early in my time studying Medicine and later have gained profound knowledge of it as well as Cell Biology and Molecular Biology through in-depth Biomedical studies. However, it is during my current study on the genetic disorder Neurofibromatosis type 1 (NF1) when my passion for the Laboratory Genetics and Genomics was lighted. My passion for the Laboratory Genetics and Genomics was lighted while I am conducting current studies on the genetic disorder Neurofibromatosis type 1 (NF1). However, it has long been deeply rooted since I was keenly aware of the importance of Genetics in health care early in my time studying Medicine and have gained profound knowledge of it as well as Cell…

    • 726 Words
    • 3 Pages
    Improved Essays