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Ariate, Lopez, Salamania, Santos, Suarez, Supranes
GeneticDisorders
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Introduction to Genetic Disorders
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Types of Genetic Disorders
Single-Gene Disorders• Caused by changes or mutations that occur in the DNA sequence of one,
single gene.• Known as Mendelian or monogenic disorder.• High chances of being passed down from parent to children
1. Autosomal Disorder - arise from one abnormal gene coming from asingle parent. Ex. Achondroplasia2. Autosomal Recessive - due to an abnormal gene from both parents.
Ex. Sickle Cell Anemia, Cystic Fibrosis3. X-linked - disorder is determined by genes on the X chromosome;
males are mainly affected while females are carriers1. X-linked dominant2. X-linked recessive Ex. Haemophilia
4. Y-linked - mutation or abnormality seen only on Y chromosome; onlymales are affected. Ex. Hypertrichosis
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Types of Genetic Disorders
Multifactoral• Caused by a combination of factors leading to mutationsin multiple genes.• The impact of the environment on the genetic apparatus
is the key in making genetic predisposition of disease tomanifest1. Cancer - the uncontrolled growth of abnormal
cells in the body.
2. Autism - a developmental disorder that appearsin the first 3 years of life, and affects the brain'snormal development of social and communicationskills.
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Types of Genetic DisordersChromosomal Abnormalities•
Mutation that occurs in chromosomes can lead to various changes in geneticinformation.• Chromosomal abnormalities like aneuploidy, chromosomal sequence deletion,
inversion of chromosomal sequences
1. Human disorders due to chromosome alterations inautosomes (Chromosomes 1-22) Ex. Down syndrome (trisomy 21),Patau syndrome (trisomy 13), Edward’s syndrome ( trisomy 18)
2. Nondisjunction of the sex chromosomes (X or Y chromosome)Ex. Monosomy X (Turner's syndrome), Metafemale , Jacob’s,Klinefelter’s syndrome
3. Alterations in chromosome structure1. Deletion - portion of one chromosome is lost during cell division.That chromosome is now missing certain genes. When thischromosome is passed on to offspring the result is usually lethal dueto missing genes. Ex. Cri du Chat
2. Duplication - if the fragment joins the homologous chromosome,then that region is repeated. Ex. Fragile X
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Types of Genetic Disorders
Mitochondrial• considered rare at this time and is due to
mutations in the non-chromosomal DNAof mitochondriaEx. Leber's hereditary optic
neuropathy (LHON)
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Treatments for Genetic Disorders
Kinds of Treatment:• Classical forms of treatment• Enzyme replacement therapy• Transplantation of cells and organs• Gene therapy
–
Germ line gene therapy – Somatic cell gene therapy
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Treatments for Genetic Disorders
Classical Forms of Treatment(i) Restrictive intake of specific dietary
components
(ii) Binding of metabolites “blocked” up -stream of the metabolic hindracnce(iii) oral replacement of enzymic cofactors in
hereditary conditions(iv) modification of activity of the
malfunctioning enzyme
(v) Use of chelating agents
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Treatments for Genetic Disorders
Enzyme Replacement Therapy• Enzyme is administered intramuscularly
or intravenously taken up by specific
target cell lysosomes• Efficiency is not very high• Can be taken up by other cells destroyed
by target cells themselves
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Treatments for Genetic Disorders
Transplantation of Cells and Organs• Example is Bone Marrow Transplant – Can replace defective lymphocytes in
severe combined immune deficiency(SCID) – Kupffer cells in the liver and microglial
cells in the central nervous system comefrom the bone marrow• Liver transplantation
–
Limited due to shortage of donor organs
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Treatments for Genetic Disorders
Gene Therapy• Mutant genes need to be replaced by
normal genes to code for functionalproteins
Germ line gene therapyOne-cell embryos injected with DNAInherited in Mendelian fashion
Somatic cell gene therapyBased on the discovery that DNA attached to aretrovirus can be incorporated in the genome of
cells
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Applications of Genetic Disorders
Genetic Testing:Genetic tests look for alterations in a
person's genes or changes in the level orstructure of key proteins coded for byspecific genes.
- National Human Genome Research Institute
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Applications of Genetic Disorders
Types of Genetic Tests:• Gene tests (individual genes or relatively
short lengths of DNA or RNA are tested)•
Chromosomal tests (wholechromosomes or very long lengths of DNAare tested)
– Karyotype – FISH Analysis
• Biochemical tests (protein levels or
enzyme activities are tested)
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Applications of Genetic Disorders
Information from Genetic Testing:• Give a diagnosis if someone has symptoms.• Show whether a person is a carrier for a
genetic disease. Carriers have an alteredgene, but will not get the disease. However,they can pass the altered gene on to theirchildren.
• Prenatal Testing - Help expectant parentsknow whether an unborn child will have agenetic condition.
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Applications of Genetic Disorders
Information from Genetic Testing:• Newborn Screening - Screen newborn
infants for abnormal or missing proteinsthat can cause disease.
• Show whether a person has an inheriteddisposition to a certain disease beforesymptoms start.
• Pharmacogenetics - Determine the type ordose of a medicine that is best for a certainperson.
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Applications of Genetic Disorders
Why decide to be tested? – Health – Practical Preparations*Remember to consult legitimate professionals
Genetic Testing in the Philippines:•
Institute of Human Genetics (UP Manila)• Ambica
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Applications of Genetic Disorders Newborn Screening Act of 2004 (R.A. 9288)
• Currently Screened Conditions: – Congenital Hypothyroidism – Congenital Adrenal Hyperplasia – Phenylketonuria, Galactosemia – Glucose-6-Phosphate Dehydrogenase Deficiency *
• Newborn Screening Centers (NSCs): – NSC- National Institutes of Health in Manila –
NSC- Visayas in Iloilo City – NSC-Mindanao in Davao City; and – NSC-Central Luzon in Angeles City
• Statistics (As of December 2010) – 2,389,959 babies have undergone NBS (DOH)
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Recent Developments and Discoveries
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Genetic Disorders in the Philippines
X-linked dystonia - parkinsonism or“ Lubag ”
• X-linked dystonia-parkinsonism is amovement disorderthat has been found
only in people ofFilipino descent. Thiscondition affects menmuch more often than
women.
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Genetic Disorders in the Philippines X-linked dystonia - parkinsonism or “ Lubag ”
• Reported in more than 500 people of Filipino descent,• Mother's ancestry to the island of Panay in the Philippines.• The prevalence of the disorder is 5.24 per 100,000 people on the
island of Panay.• Mutations in and near the TAF1 gene can cause X-linked
dystonia-parkinsonism. The TAF1 gene provides instructions formaking part of a protein called transcription factor IID (TFIID).This protein is active in cells and tissues throughout the body, where it plays an essential role in regulating the activity of mostgenes.
• Molecular genetic analysis indicates that the mutationresponsible for X-linked dystonia-parkinsonism was introducedinto the Olongo ethnic group of Panay more than 2,000 yearsago.
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Genetic Disorders in the Philippines
Kawasaki Disease Among Filipino-AmericanChildren in San Diego A clinical research in San Diegoindicates that Filipino children with Kawasaki Disease (KD) areat a higher risk for inflammationof the blood vessels of the heartthan those of other Asian and
non-Asian backgrounds.(Science Daily, 2011)• Nearly 24 % of Filipino children with KD in San Diego County werefound to have aneurysms compared to 10.5 % of children of other Asian descent.
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Genetic Disorders in the Philippines Institute of Human Genetics (IHG)
– 1990 – Medical Genetics Unit of the Universityof the Philippines College of Medicine
– 1999 – one of the service and research
oriented institutes of the National Institutes ofHealth-University of the Philippines Manila(NIH-UP).
– the largest provider of genetic services in thecountry.
– Newborn Screening, Cytogenetics, ClinicalGenetics, Molecular and Cancer Genetics, and
Biochemical Genetics
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Genetic Disorders in the Philippines• IHG houses the central
laboratory of the NationalComprehensive NewbornScreening System.
• Providing the most advancednewborn screening tests for apanel of five metabolicdisorders which includecongenital hypothyroidism,congenital adrenalhyperplasia, phenylketonuria,galactosemia and glucose-6-phosphate dehydrogenase
deficiency.
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Genetic Disorders in the Philippines
Figure 1. The National Newborn Screening Coverage from 1996 to2010. The Percent Coverage was determined using the Live birth data fromthe 2007 Philippine Statistical Yearbook (1.7 Million live births).
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Genetic Disorders in the Philippines
Figure 2. The Prevalence Rate of the NBS Panel Disorders. G6PDDeficiency has the incidence rate with one confirmed case in every 52newborns screened.
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References• N. Hjelm , “Treating genetic diseases,” HKMJ 2(3), 1996. • http://ghr.nlm.nih.gov/condition/x-linked-dystonia-parkinsonism• http://www.sciencedaily.com/releases/2011/05/110506190124.htm• http://www.dystonia.ie/page.asp?Page=41&Menu=32• https://sites.google.com/site/vylhphilippines/announcements/2010NBScoverageup
date• http://ihg.upm.edu.ph/
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