Genetic Disorders

• Results from abnormal numbers or structure of chromosomes or in the DNA

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Three main classes of genetic disorders

• Single gene disorders- mutations in single genes often causing loss of function

• Multifactorial conditions- variants in genes interacting with the environment and causing alteration of function

• Chromosomal disorders- causing chromosomal imbalance and alteration in gene dosage

How common are genetic disorders

• We all carry genes that are potentially hazardous. Some are hidden in recessive form and we may never know that we carry them. Some will only exert their influence through interactions with environmental triggers. Others are manifest even before our birth.

Changes in chromosome structure

• Deletions- part of a chromosome is lost or deleted

• Duplications- part of a chromosome is doubled or duplicated

• Translocations- chromosome moves and pairs with another. As long as no genetic information is gained or lost, the individual is not affected

Autosomal dominant or recessive inheritance

• Autosomal dominant disorders- inheriting a single copy of an altered gene on a non sex chromosome

• Example- Huntington’s disease• Autosomal recessive disorders- inheriting a copy

of an altered gene found on a non sex chromosome from EACH parent. “carriers” can result. Over 700 disorders

• Example- hemophilia, muscular dystrophy, sickle cell anemia, PKU, cystic fibrosis

Sex linked disorders

• Altered genes lie on the X chromosome• 100 disorders • Normally seen in males• Usually inherited from a mother because she

is a carrier and asymptomatic

Down’s Syndrome

• Trisomy 21- only trisomy compatible with life• Usually caused by nondisjunction during

gamete formation- 90% from the egg• 1:600 births• Developmentally disabled, diamond shaped

eyes, enlarged tongue

Edward’s syndrome

• Trisomy 18• 1:6,000 births• Life expectancy is less than 10 months• Microcephaly, low set ears, organ

malformations, malformed hands and feet

Patau’s syndrome

• Trisomy 13• 1:7,500 births• Usually fatal within first year• Very severe mental retardation, low set ears,

common breathing and heart problems

Cri du chat syndrome

• Deletion of arm of chromosome 5. most common deletion disorder

• 1:50,000 births• Microcephaly leading to severe mental

retardation• Usually fatal within first year

William’s Syndrome

• Deletion of piece of chromosome 7• 1:50,000 births• Growth retardation• Mental retardation• “elf-like” appearance• Lack a protein needed to strengthen blood

vessels- therefore they have disorders of circulatory system and heart defects

Turner’s syndrome

• Deletion of one X chromosome• “monosomy”• Gender is female• 1:2,500 births• Normal lifespan• Sterile, rudimentary ovaries• Failure to develop sexually, webbed neck,

cardiovascular abnormalities• No mental retardation

Klinefelter’s Syndrome

• XXY- caused by nondisjunction in meiosis• Only males• 1:1,000 births• Infertile• Developmentally disabled, mild mental

disability possible, rudimentary female secondary sexual characteristics develop

• Hormone therapy treatment available

Jacob’s syndrome

• XYY• Abnormal sperm is cause• Clinical phenotype is normal• Extremely tall• Very mild learning disorders

Poly “X”

• XXX• Also known as trisomy X and aneuploidy X• 1:1,000 births• Normal clinical phenotype other than taller

than average and poor social skills

Tay Sachs Disease

• Autosomal recessive disease• Lipid accumulation in brain, seizures,

blindness• No cure or treatment• Death by age 4• Only about 16 cases per year in USA

Cystic fibrosis

• Autosomal recessive disease• Congestion in lungs, blockage of digestive

tract, pneumonia due to lack of

Hemophilia• X linked disorder• Absence or minimal presence of a clotting factor • “free bleeder”• Hemophilia is a bleeding disorder that slows the blood clotting

process. People with this condition experience prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled. In severe cases of hemophilia, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of hemophilia do not involve spontaneous bleeding, and the condition may not become apparent until abnormal bleeding occurs following surgery or a serious injury.

PKU

• Recessive disorder of amino acid metabolism• 1:15,000 births • Homozygous infants accumulate toxic

substances in their brains that can impair mental ability by affecting the brain’s development

• PKU “phenylalanine” is ingested in diet• Can be diagnosed in babies, so feed a low PKU

diet.- heel prick test

PKU test

Huntington’s Disease

• Dominant allele disorder• Everyone who inherits the gene will get the

disease• Deterioration of nervous system• Part of the brain that controls thinking,

emotion, and movement• Onset after age 30-40

Sickle Cell Disease

• Autosomal recessive allele• Disorder of the red blood cells- irregular shape• Sickle cell disease prevents oxygen from

reaching the organs and the tissue begin to die. The spleen is often destroyed in these patients resulting in some loss of immune function and resulting in infections

Muscular dystrophy

• X linked disorder• Wasting away of muscles• Muscle weakness intensifies until the

individual is confined to a wheelchair

Alzheimer’s Disease

• Gradually lose their memories and intellectual functions

• Autosomal dominant• Researchers believe it may be caused by an

extra copy or mutant alleles of a gene located on chromosome 19 or 21

Diagnosing certain disorders

• CVS• Amniocentesis• Newborn genetic screening

CVS• Chorionic Villus Sampling (CVS)• Chorionic villus sampling (CVS) is a test done during early pregnancy that can find certain problems with

your baby (fetus). It is generally done when either you or the father has a disease that runs in the family (genetic disorder). It may also be done when you are over age 35-being over 35 increases your chance of having a baby with a chromosome defect.

• Chorionic villi are tiny finger-shaped growths found in the placenta. The genetic material in chorionic villus cells is the same as that in the baby's cells. During CVS, a sample of the chorionic villus cells is taken for biopsy. The chorionic villus cells are checked for problems. The procedure is generally done late in the first trimester, most often between the 10th and 12th weeks.

• The chorionic villus sample can be collected by putting a thin flexible tube (catheter) through the vagina and cervix into the placenta. The sample can also be collected through a long, thin needle put through the belly into the placenta. Ultrasound is used to guide the catheter or needle into the correct spot for collecting the sample.

• If you have a family history of certain diseases, CVS can be used to find genetic disorders, such as Tay-Sachs disease or hemophilia. It can also find chromosomal birth defects, such as Down syndrome. CVS cannot find neural tube defects and it cannot be used to see if the baby's lungs are mature.

• Chorionic villus sampling can be done earlier in pregnancy (at 10 to 12 weeks) than amniocentesis (usually done at 15 to 20 weeks). This allows you to know the health of your baby and make an earlier decision whether to continue or end the pregnancy. Results of CVS can be available sooner than amniocentesis results

• http://www.youtube.com/watch?v=sxEf_ddmpZk

amniocentesis

• Amniocentesis is a prenatal test in which a small amount of amniotic fluid is removed from the sac surrounding the fetus and is tested. The sample of amniotic fluid (less than one ounce) is removed through a fine needle inserted into the uterus through the abdomen, under ultrasound guidance. The fluid is then sent to a laboratory for analysis. Different tests can be performed on a sample of amniotic fluid, depending on the genetic risk and indication for the test

• http://www.youtube.com/watch?v=GZoswKIa4ic

Newborn genetic screening

• Newborn screening varies from state to state. All states must screen for at least 21 disorders by law, and some states test for 30 or more. Parents can ask their doctor about expanded (supplemental) screening if they live in an area that screens for a limited number of disorders

• Newborn screening is the practice of testing all babies for certain disorders and conditions that can hinder their normal development. Babies with these conditions appear healthy at birth but can develop serious medical problems later in infancy or childhood. Early detection and treatment can help prevent intellectual and physical disabilities and life-threatening illnesses.

• Newborn screening usually begins with a blood test 24 to 48 hours after the baby is born. The test is performed by pricking the baby's heel to collect a few drops of blood. The blood is placed on a special piece of paper and sent to a laboratory for analysis. Parents can ask for a copy of the test results, which are sent to the baby's doctor or clinic.

Newborn testing

• http://www.youtube.com/watch?v=j20YP0bUaMg

Genetic disorders and diseases

• http://www.youtube.com/watch?v=sxEf_ddmpZk

18 things you should know about genetics

• http://www.youtube.com/watch?v=bVk0twJYL6Y