Establishing Novel Detection Techniques for Various Genetic-Related Diseases by Applying DHPLC Platform.

2014-08-27 03:51:30 | BioPortfolio


In this, here we want to present a new method for analysis variation in gene copy number for patients and carriers of SMA. This is a relative quantitation method and, therefore, relies on the inclusion of one or more internal control or reference sequences; quantitation of DNA is relative to this reference sequence of known copy number. A peak height from within a potentially duplicated or deleted target region is amplified simultaneously with a disomic reference region in a multiplex PCR system.


Proximal spinal muscular atrophy is an autosomal recessive disorder with an overall incidence of 1 in 10000 live births and a carrier frequency of 1 in 50. This severe neuromuscular disease is characterized by a degeneration and loss of alpha motor neurons of the spinal cord anterior horn cells, which results in progressive symmetrical weakness, atrophy of the proximal voluntary muscles, and infant death. Here, we present a new, rapid, simple and high reliable method to detect the SMN1 deletion and to determine the copy number of the SMN1 and SMN2 by denaturing high-performance liquid chromatography (DHPLC). We demonstrate that this assay is able to accurately distinguish 2 gene copies from 4 gene copies and it can identify SMA carriers and normal populations by the accurate determination of SMN copy number.

Fecal DNA testing is a promising tool for colorectal cancer screening. Researchers have shown that DNA to be a good marker since it is stable in the stool; it shed continuously; and, through the use of amplification tests, it can be detected in minute amounts. Many DNA mutations associated with the process of colon cancer carcinogenesis have been characterized. K-ras oncogene, adenomatous polyposis coli (APC), p53, and microsatellite markers are examples of genes targeted as DNA markers in stool testing because they are critical to the control of colorectal cell growth. Early clinical studies have shown that multitarget DNA testing has a 71% to 91% sensitivity for detection of cancer and a 55% to 82% sensitivity for detecting adenoma 1cm or larger. We design this study, by using the automated DHPLC analysis and the microsatellite markers set already at first, to stepwisely set-up a high throughput but sensitive and specific screen method for colorectal cancer screen.

Neonatal hyperbilirubinemia is a common problem and is of concern not only to pediatricians but also to the parents of neonates. Two key enzymes, UDP-glucuronosyl transferase 1A1 and heme oxygenase-1 (HO-1), that involve bilirubin metabolism are highly noticed. First, UGT1A1 is the key enzyme for bilirubin conjugation and mutations of UGT1A1 cause the unconjugated hyperbilirubinemias known as Crigler-Najjar syndrome and Gilbert's syndrome. The high allele-frequency of Gly71Arg and promoter polymorphism in UGT1A1 gene was found to be responsible for neonatal hyperbilirubinemia without obvious cause. Second, HO-1 is a rate-limiting enzyme in the heme metabolism and allows for the degradation of heme to biliverdin. Recently, Maruo et al. demonstrated that (16/17) breastfed Japanese infants with apparent prolonged jaundice had at least one mutation of the UGT1A1. These data suggested that that defects of UGT1A1 may be an underlying cause of the prolonged unconjugated hyperbilirubinemia associated with breast milk. However, to date the association between breastfed infants with severe hyperbilirubinemia and UGT1A1 gene mutation is still unclear. In this study, we will analyze the UGT1A1 and HO-1 genes of infants with unconjugated hyperbilirubinemia associated with breast milk to ascertain whether genetic factors are involved.

This project will contribute to apply DHPLC on establishing various novels, fast, and reliable applications for diagnosis of SMA and carrier detection of SMN1 and SMN2 genes, sensitive and specific screen method for colorectal cancer screen, and analyze the UGT1A1 and HO-1 genes of infants with unconjugated hyperbilirubinemia associated with breast milk.

Study Design

Observational Model: Case Control, Primary Purpose: Screening, Time Perspective: Longitudinal, Time Perspective: Prospective


Spinal Muscular Atrophy


Dept of Medical Genetics;National Taiwan University Hospital




National Taiwan University Hospital

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:51:30-0400

Clinical Trials [1514 Associated Clinical Trials listed on BioPortfolio]

A Study of CK-2127107 in Patients With Spinal Muscular Atrophy

The primary objective of this study is to demonstrate a pharmacodynamic effect of CK-2127107 on measures of skeletal muscle function or fatigability in patients with Spinal Muscular Atroph...

French Registry of Patients With Infantile-onset Spinal Muscular Atrophy

IO-SMA-Registry is a prospective, longitudinal and observational study which objective is to collect prospectively information on longevity, psychomotor development and respiratory functio...

A Study to Evaluate Long Term Safety, Tolerability, and Effectiveness of Olesoxime in Patients With Spinal Muscular Atrophy

The purpose of this study is to evaluate the safety of olesoxime in participants with spinal muscular atrophy, focusing on the nature, frequency, and severity of adverse events, as well as...

Motor Development and Orthoses in Spinal Muscular Atrophy (SMA)

Spinal Muscular Atrophy (SMA) is neurodegenerative disease of anterior horn cells of spinal cord and represents the second more frequent pathology in childhood. According to the age of ...

An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy (TOPAZ)

The TOPAZ study will assess the safety and efficacy of SRK-015 in later-onset Spinal Muscular Atrophy (SMA Type 2 and Type 3) in pediatric and adult patients.

PubMed Articles [2591 Associated PubMed Articles listed on BioPortfolio]

Homozygous mutation causes congenital distal spinal muscular atrophy and arthrogryposis.

To identify the genetic cause of disease in a form of congenital spinal muscular atrophy and arthrogryposis (CSMAA).

Revised Upper Limb Module for Spinal Muscular Atrophy: 12 month changes.

The aim of the study was to assess 12 month changes in upper limb function in patients affected by spinal muscular atrophy type 2 and 3.

Systemic nature of spinal muscular atrophy revealed by studying insurance claims.

We investigated the presence of non-neuromuscular phenotypes in patients affected by Spinal Muscular Atrophy (SMA), a disorder caused by a mutation in the Survival of Motor Neuron (SMN) gene, and whet...

Nusinersen in type 1 Spinal Muscular Atrophy: 12-month real world data.

The aim of the study was to report 12-month changes after treatment with Nusinersen in a cohort of 85 type I Spinal Muscular Atrophy patients of age ranging from 2 months to 15 years and 11 months.

Efficacy and Safety of Valproic Acid for Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis.

Spinal muscular atrophy (SMA) is a neuromuscular disorder classified into four types based on the age of onset of the disease. Early onset is correlated with a higher mortality rate, mainly due to res...

Medical and Biotech [MESH] Definitions

A group of disorders marked by progressive degeneration of motor neurons in the spinal cord resulting in weakness and muscular atrophy, usually without evidence of injury to the corticospinal tracts. Diseases in this category include Werdnig-Hoffmann disease and later onset SPINAL MUSCULAR ATROPHIES OF CHILDHOOD, most of which are hereditary. (Adams et al., Principles of Neurology, 6th ed, p1089)

An X-linked recessive form of spinal muscular atrophy. It is due to a mutation of the gene encoding the ANDROGEN RECEPTOR.

Disorders characterized by an abnormal reduction in muscle volume due to a decrease in the size or number of muscle fibers. Atrophy may result from diseases intrinsic to muscle tissue (e.g., MUSCULAR DYSTROPHY) or secondary to PERIPHERAL NERVOUS SYSTEM DISEASES that impair innervation to muscle tissue (e.g., MUSCULAR ATROPHY, SPINAL).

Diseases characterized by a selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In AMYOTROPHIC LATERAL SCLEROSIS there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes (see MUSCULAR ATROPHY, SPINAL) the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy (BULBAR PALSY, PROGRESSIVE), the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation. (Adams et al., Principles of Neurology, 6th ed, p1089)

Longitudinal cavities in the spinal cord, most often in the cervical region, which may extend for multiple spinal levels. The cavities are lined by dense, gliogenous tissue and may be associated with SPINAL CORD NEOPLASMS; spinal cord traumatic injuries; and vascular malformations. Syringomyelia is marked clinically by pain and PARESTHESIA, muscular atrophy of the hands, and analgesia with thermoanesthesia of the hands and arms, but with the tactile sense preserved (sensory dissociation). Lower extremity spasticity and incontinence may also develop. (From Adams et al., Principles of Neurology, 6th ed, p1269)

More From BioPortfolio on "Establishing Novel Detection Techniques for Various Genetic-Related Diseases by Applying DHPLC Platform."

Quick Search


Relevant Topics

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

DNA sequencing
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. During DNA sequencing, the bases of a small fragment of DNA are sequentially identified from signals emitted as each fragment is re-synthesized from a ...

Acne Dermatology Eczema Psoriasis Wound Care Dermatology is the medical specialty concerned with the diagnosis and treatment of skin disorders (Oxford Medical Dictionary). As well as studying how the skin works, dermatology covers...

Searches Linking to this Trial