Mutations & Genetic Disorders IN 141 Headings Vocabulary Important Information

Mutations Mutation:  Any mistake or change in the DNA sequence Point mutation:  Change in one nitrogen base in DNA  Ex: albinism

 Changes in chromosome structure 1) INVERSION:  the order of genes on a chromosome is inverted Chromosomal Mutation: 2) TRANSLOCATION: the movement of a chromosome fragment to a nonhomologus chromosome

3. DELETION  Loss of a few bases  Loss of large regions of a chromosome 4. DUPLICATION  Duplication of a few bases  Duplication of large regions of a chromosome

Crossing Over  Occurs when chromosomes exchange genes.  2 chromosomes overlap.  Some genes cross over and switch places

NONDISJUNCTION Nondisjunction:  chromosome pair fails to separate properly during meiosis Monosomy:  gamete has 1 less chromosome than it should  45 chromosomes is the result  Ex: Turner syndrome  Missing a sex chromosome

Trisomy:  Gamete has 1 more chromosome than it should  Result is 47 chromosomes  Ex: Down’s Syndrome  Extra #21 chromosome

Methods of Detection Ultrasound:  Sound waves are used to generate an image of the unborn child.  Used to detect abnormalities of limbs, organs, etc. Chorion villi sampling: Take sample of the chorion –(membrane surrounding fetus) KaryotypingChemical tests and Karyotyping performed

Amniocentesis: Fluid surrounding the fetus is drawn out by needle Fetal cells are collected and grown in a lab. Chromosomes can be then Karyotyped

Autosomal Disorders  Down’s Syndrome (Trisomy 21)  Patau’s Syndrome (Trisomy 13)  Edward’s Syndrome (Trisomy 18)

Down’s Syndrome (DS)  Excess # 21 chromosome  Prenatal testing can be done  Result of chromosomal mutation  1 in 900 people born with this  Likelihood of having a child with DS increases with advancing maternal age  Symptoms: mental retardation, upward slant to eyes, small mouth, abnormal ear shape, decreased muscle tone  No cure

Patau’s Syndrome & Edward’s Syndrome  Cardiac abnormalities  Very severe conditions  Most affected infants die during first few weeks of life

Deletion Disorders  Angelman Syndrome  Prader-Willi Syndrome

Angelman Syndrome  Inappropriate laughter with convulsions  Poor coordination  Mental retardation

Prader-Willi Syndrome  Extremely floppy  Obesity (constantly hungry)  Mild mental retardation

Sex Chromosome Disorders  Klinefelter’s Syndrome  Turner’s Syndrome  Fragile X Syndrome

Klinefelter’s Syndrome  47, XXY  1 in 1000 male live births  Mild learning difficulties  Taller than average with long lower limbs  Show mild enlargement of breasts  Infertile (absence of sperm)  Treat with testosterone

Turner’s Syndrome  45, X  Low incidence  Look normal  Ovarian failure  Normal intelligence  Short stature  Estrogen therapy

Fragile X Syndrome  Most common inherited cause of mental retardation  1 in 2000 males  High forehead, prominent jaw, autism  Gap in X chromosome

Single Gene Disorders  Cystic Fibrosis  Hemophilia  Sickle Cell Anemia  Phenylketonuria

Cystic Fibrosis (CF)  Recessive disorder  Mutation stops production of protein in lung cells, pancreas  Thick mucus, bacterial infections in lung  “sweat test”  Most common in Caucasians (1 in 3300)  Chest percussions, diet supplements  Shortened life expectancy

Hemophilia  Sex-linked  Failure of blood to clot  Rare in females  Injections with clotting factors to stop bleeding episodes  $350,000 a year in treatment

Sickle Cell Anemia  Mutation in blood protein  “sickle” shape to RBC  Screening tests  Most common in African-Americans (1 in 375)  Pain associated with blocked vessels, causes anemia (fatigue)  Common where mosquito-borne malaria is present

PKU  Mutation disrupts function of enzyme  Leads to high phenylalanine levels in brain (poisons)  Mental retardation, epilepsy  Screening newborns (heel prick)  1 in 10,000 Caucasian births  Extremely rare in African-Americans  Look normal  Need low-protein diet, smelly formulas

Self Quiz: Quick Check for Understanding  1. Which of the following is an X-linked disorder?  A. AngelmanB. hemophilia c. Down syndrome  2. How is PKU tested for?  A. amniocentesisb. heel prick c. X-ray  3. How are CF patients treated?  A. testosterone injectionsb. chest percussions  4. Turner’s Syndrome is  A. 45, Xb. 46, XXc. 47, XXY  5. Patients with Klinefelter’s Syndrome are  A. all maleb. all femalec. male or female