Mutations & Genetic Disorders PDF

Mutations & Genetic Disorders  Mutations Mutation: Any mistake or change in the DNA sequence Point mutation: Change in one nitrogen base in DNA Ex: albinism  Chromosomal Mutation: Changes in chromosome structure 1) INVERSION: the order of genes on a c...

Mutations & Genetic Disorders  Mutations Mutation: Any mistake or change in the DNA sequence Point mutation: Change in one nitrogen base in DNA Ex: albinism  Chromosomal Mutation: Changes in chromosome structure 1) INVERSION: the order of genes on a chromosome is inverted 2) TRANSLOCATION: themovement 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 Chorion villi sampling: Take sample of the chorion –(membrane surrounding fetus) Chemical tests and Karyotyping performed Ultrasound: Sound waves are used to generate an image of the unborn child. Used to detect abnormalities of limbs, organs, etc. 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  It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th century by Jean Etienne Dominique Esquirol in 1838 and Edouard Seguin in 1844. Down syndrome was identified as a chromosome 21Trisomy by Dr. Jerome Lejeune in 1959. Down Syndrome  Patau’s Syndrome & Edward’s Syndrome Cardiac abnormalities Very severe conditions Most affected infants die during first few weeks of life TRISOMY 13 (PATAU SYNDROME)  Patau Sundrome, also known as Trisomy 13 and Trisomy D.  Is a chromosomal abnormality, a syndrome in which a patient had an additional chromosome 13 due to non- disjunction of chromosomes during meiosis.  The extra chromosome 13 disrupts the normal course of development, causing heart and kidney defects, amongst other features characteristic of Patau syndrome.  Patau syndrome affects somewhere between 1 in 10,000 and 1 in 21,700 live births. Patau syndrome TRISOMY 13 (PATAU SYNDROME) Trisomy 18 (Edward Syndrome) Edward’s Syndrome also known as Trisomy 18 (T18) or Trisome E. It is a genetic disorder caused by the presence of all of an extra 18th chromosome (Trisomy 18) due to meiotic nondisjunction. It is named after John H. Edwards, who first described the syndrome in 1960. It is the second most common autosomal trisomy, after Down Syndrome, that carries to term. Edward’s Syndrome occurs in around 1 in 6,000 live births and around 80 % of those affected are female. Features of Edward Syndrome Mental deficiency Growth retardation Prominent occiput with elongated head Webbing of the neck Short sternum Micrognathia Low-set malformed ears Ventricular septal defects Renal anomalies Clenched fists with overlapping of fingers Hypoplastic nails Edward syndrome  Deletion Disorders Angelman Syndrome Prader-Willi Syndrome Cri Du Chat  Angelman Syndrome Inappropriate laughter with convulsions Poor coordination Mental retardation  Prader-Willi Syndrome Extremely floppy Obesity (constantly hungry) Mild mental retardation Cri Du Chat  CRI DU CHAT  CRI DU CHAT also known as chromosome 5p deletion syndrome, 5p minus syndrome or Lejeune’s syndrome.  Is a rare genetic disorder due to a missing part of chromosome 5. Its name is a French term (cat-cry or call of the cat) referring to the characteristic cat-like cry of affected children.  It was first described by Jerome Lejeune in 1963. The condition affects an 1 in 50,000 live births, strikes all ethnicities, and is more common in females by a 4:3 ratio. DELETION on the short arm of chromosome 5. Cries like a CAT CRI DU CHAT  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 disordser? A. Angelman B. hemophilia c. Down syndrome 2. How is PKU tested for? A. amniocentesis b. heel prick c. X-ray 3. How are CF patients treated? A. testosterone injections b. chest percussions 4. Turner’s Syndrome is A. 45, X b. 46, XX c. 47, XXY 5. Patients with Klinefelter’s Syndrome are A. all male b. all female c. male or female