Genetic Disorders

Ariate, Lopez, Salamania, Santos, Suarez, Supranes

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 a single parent. Ex. Achondroplasia 2. Autosomal Recessive - due to an abnormal gene from both parents. Ex. Sickle Cell Anemia, Cystic Fibrosis 3. X-linked - disorder is determined by genes on the X chromosome; males are mainly affected while females are carriers 1. X-linked dominant 2. X-linked recessive Ex. Haemophilia 4. Y-linked - mutation or abnormality seen only on Y chromosome; only males are affected. Ex. Hypertrichosis

Types of Genetic Disorders

Multifactoral

Caused by a combination of factors leading to mutations in multiple genes. The impact of the environment on the genetic apparatus is the key in making genetic predisposition of disease to manifest

1. Cancer - the uncontrolled growth of abnormal cells in the body. 2. Autism - a developmental disorder that appears in the first 3 years of life, and affects the brain's normal development of social and communication skills.

Types of Genetic Disorders

Chromosomal Abnormalities

Mutation that occurs in chromosomes can lead to various changes in genetic information. Chromosomal abnormalities like aneuploidy, chromosomal sequence deletion, inversion of chromosomal sequences

1.

Human disorders due to chromosome alterations in autosomes (Chromosomes 1-22) Ex. Down syndrome (trisomy 21), Patau syndrome (trisomy 13), Edwards syndrome (trisomy 18) 2. Nondisjunction of the sex chromosomes (X or Y chromosome) Ex. Monosomy X (Turner's syndrome), Metafemale, Jacobs, Klinefelters syndrome 3. Alterations in chromosome structure 1. Deletion - portion of one chromosome is lost during cell division. That chromosome is now missing certain genes. When this chromosome is passed on to offspring the result is usually lethal due to missing genes. Ex. Cri du Chat 2. Duplication - if the fragment joins the homologous chromosome, then that region is repeated. Ex. Fragile X

Types of Genetic Disorders

Mitochondrial

considered rare at this time and is due to mutations in the non-chromosomal DNA of mitochondria Ex. 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

Treatments for Genetic Disorders

Classical Forms of Treatment

(i) Restrictive intake of specific dietary components (ii) Binding of metabolites blocked upstream 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

Treatments for Genetic Disorders

Enzyme Replacement Therapy
Enzyme is administered intramuscularly or intravenouslytaken up by specific target celllysosomes Efficiency is not very high Can be taken up by other cells destroyed by target cells themselves

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 come from the bone marrow Liver transplantation Limited due to shortage of donor organs

Treatments for Genetic Disorders

Gene Therapy
Mutant genes need to be replaced by normal genes to code for functional proteins

Germ line gene therapy One-cell embryos injected with DNA Inherited in Mendelian fashion Somatic cell gene therapy Based on the discovery that DNA attached to a retrovirus 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 or structure of key proteins coded for by specific genes.

-National Human Genome Research Institute

Applications of Genetic Disorders

Types of Genetic Tests:

Gene tests (individual genes or relatively short lengths of DNA or RNA are tested) Chromosomal tests (whole chromosomes or very long lengths of DNA are tested) Karyotype FISH Analysis Biochemical tests (protein levels or enzyme activities are tested)

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 altered gene, but will not get the disease. However, they can pass the altered gene on to their children. Prenatal Testing - Help expectant parents know whether an unborn child will have a genetic condition.

Applications of Genetic Disorders

Information from Genetic Testing:

Newborn Screening - Screen newborn infants for abnormal or missing proteins that can cause disease. Show whether a person has an inherited disposition to a certain disease before symptoms start. Pharmacogenetics - Determine the type or dose of a medicine that is best for a certain person.

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

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 dystoniaparkinsonism is a movement disorder that has been found only in people of Filipino descent. This condition affects men much 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 for making 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 most genes. Molecular genetic analysis indicates that the mutation responsible for X-linked dystonia-parkinsonism was introduced into the Olongo ethnic group of Panay more than 2,000 years ago.

Genetic Disorders in the Philippines

Kawasaki Disease Among Filipino-American Children in San Diego

A clinical research in San Diego indicates that Filipino children with Kawasaki Disease (KD) are at a higher risk for inflammation of the blood vessels of the heart than those of other Asian and non-Asian backgrounds. (Science Daily, 2011)
Nearly 24 % of Filipino children with KD in San Diego County were found 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 University of the Philippines College of Medicine 1999 one of the service and research oriented institutes of the National Institutes of Health-University of the Philippines Manila (NIH-UP). the largest provider of genetic services in the country. Newborn Screening, Cytogenetics, Clinical Genetics, Molecular and Cancer Genetics, and Biochemical Genetics

Genetic Disorders in the Philippines

IHG houses the central laboratory of the National Comprehensive Newborn Screening System. Providing the most advanced newborn screening tests for a panel of five metabolic disorders which include congenital hypothyroidism, congenital adrenal hyperplasia, phenylketonuria, galactosemia and glucose-6phosphate dehydrogenase deficiency.

Genetic Disorders in the Philippines

Figure 1. The National Newborn Screening Coverage from 1996 to 2010. The Percent Coverage was determined using the Live birth data from the 2007 Philippine Statistical Yearbook (1.7 Million live births).

Genetic Disorders in the Philippines

Figure 2. The Prevalence Rate of the NBS Panel Disorders. G6PD Deficiency has the incidence rate with one confirmed case in every 52 newborns 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/