Genetic Disorders.pptx

8/14/2019 Genetic Disorders.pptx

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Ariate, Lopez, Salamania, Santos, Suarez, Supranes

GeneticDisorders



Introduction to Genetic Disorders



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




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.



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




Mitochondrial• considered rare at this time and is due to

mutations in the non-chromosomal DNAof mitochondriaEx. Leber's hereditary optic

neuropathy (LHON)



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




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




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




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




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



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




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)




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.




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.




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



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)



Recent Developments and Discoveries



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.



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.




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.



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



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.




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).




Figure 2. The Prevalence Rate of the NBS Panel Disorders. G6PDDeficiency has the incidence rate with one confirmed case in every 52newborns screened.



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/

Genetic Disorders.pptx

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