Genetic Disorders

1. Genetic Disorders Things Can Go Wrong With DNA and/or Chromosomes

2. I. Overview of DNA Structure A. Review 1. A gene is a segment of DNA that codes for a particular protein 2. Proteins determine the physical traits of an organism 3. In humans, DNA is organized into 23 pairs of homologous chromosomes B. DNA Structure 1. The basic building block of DNA is a nucleotide 2. Nucleotide chains are held together to form a double helix 3. Nucleotides are represented using the letters A,T,C,G 4. The number and sequence of nucleotides in DNA determine which protein is made!

3. One nucleotide Nucleotide Structure DNA Structure

4. II. DNA Based Disorders A. Dysfunctional Genes 1. a gene can be missing some of its nucleotides or some of the nucleotides present may be in the wrong order • the protein made from that gene may not work properly B. Missing Genes 1. a person can be born missing an entire gene or missing so much of a particular gene that there is no gene product (protein) produced

5. II. DNA Based Disorders C. Examples of DNA Based Disorders 1. Sickle-cell anemia • Caused by a substitution of one nucleotide in the allele for normal hemoglobin, producing an abnormal shape. - Hemoglobin is the oxygen carrying protein in red blood cells • Under stress, sickle-cell shaped red blood cells become more rigid and tend to become stuck in capillaries, leading to tissue death • Most common among individuals with African decent - People with sickle cell anemia have been shown to be resistant to malaria - Sickle cell anemia is most prevalent among countries with higher incidences of malaria

6. II. DNA Based Disorders Normal Red Blood Cell Sickle Cell • Huntington’s Disease • Produced by a single dominant allele • A gradual change of the nervous system occurs around the age of 30 or 40 • Marked by a painful, progressive loss of muscle control and mental function until death occurs

7. III. Chromosomal Based Disorders • Causes 1. Nondisjunction • during meiosis I, homologous chromosomes do not separate properly • Results in an extracopy of a chromosome in one cell, and a loss of that chromosome from another

8. III. Chromosomal Based Disorders • Results • When these gametes fuse with a normal gamete during fertilization, the resulting person will have an abnormal number of chromosomes • A monosomic cell has one missing chromosome • usually lethal except for: Turner's syndrome (monosomy XO). • A trisomic cell has one extra chromosome

9. III. Chromosomal Based Disorders • Nondisjunction of Sex Chromosomes • Affects approximately 1 birth in every 1000 • Genes critical to all embryonic development are on the X chromosome • absence of an X chromosome is lethal • absence of a Y chromosome is not lethal • Individuals can survive if they have an extra sex chromosome

10. III. Chromosomal Based Disorders D. Disorders involving Sex Chromosomes 1. Klinefelter Syndrome  males with extra X-chromosomes •  can be XXY, XXXY, OR XXXXY • 1/500 births • phenotypically male with some female tendencies - particularly physical characteristics • enlarged breasts, low body hair count, small testes, long legs, thin, sterile • mental retardation when there are more than 2 X-chromosomes

11. III. Chromosomal Based Disorders D.Disorders involving Sex Chromosomes cont. 2. Triple X and Quad X Syndrome •  females with 1 or 2 extra X-chromosomes (XXX, or XXXX) • 1/700 female births • sometimes there is no visible difference from XX females • limited fertility • XXXX females are always mentally retarded • 3. Turner Syndrome •  females with only one X-chromosome • 1/2500 live female births • more than 90% self abort • no ovaries, short, shield-like chestlow set ears, webbed neck • no mental deficiencies

12. III. Chromosomal Based Disorders E. Nondisjunction of Autosomal (non-sex) Chromosomes • Can affect chromosomes #1 - #22 • There are only 3trisomes that result in a baby that can survive for a time after birth • The others are too devastating and the baby usually dies in utero.

13. III. Chromosomal Based Disorders F. Disorders Involving Autosomal Chromosomes 1. Down Syndrome  one extra chromosome 21 -written as (47,+21) • 1/700 births of individuals of European decent • 1/6 die within the first year • average life expectancy is 16 years • lower than average mentality • many physical deviations such as shorter than average height, broad forehead, round head, open mouth, etc.

14. III. Chromosomal Based Disorders F. Disorders Involving Autosomal Chromosomes 2. Edwards syndrome is caused by trisomy (three copies) of chromosome 18. Results in: kidney malformations, structural heart defects at birth (i.e., ventricular septal defect, atrial septal defect, patent ductus arteriosus), intestines protruding outside the body (omphalocele), esophageal atresia, mental retardation, developmental delays, growth deficiency, feeding difficulties, breathing difficulties, and arthrogryposis (a muscle disorder that causes multiple joint contractures at birth). Also,a small head (microcephaly) accompanied by a prominent back portion of the head (occiput), low-set, malformed ears, abnormally small jaw (micrognathia), cleft lip/cleft palate, upturned nose, narrow eyelid folds (palpebral fissures), widely-spaced eyes (ocular hypertelorism), drooping of the upper eyelids (ptosis), a short breast bone, clenched hands, underdeveloped thumbs and or nails, absent radius, webbing of the second and third toes, clubfoot or Rocker bottom feet, and undescended testicles in males. X

15. III. Chromosomal Based Disorders F. Disorders Involving Autosomal Chromosomes 3. Patau syndrome is caused by trisomy of #13. * mental & motor challenged * polydactyly (extra digits) * microcephaly * low-set ears * holoprosencephaly (failure of the forebrain to divide properly). * heart defects * structural eye defects, including microphthalmia, Peters anomaly, cataract, iris and/or fundus (coloboma), retinal dysplasia or retinal detachment, sensory nystagmus, cortical visual loss, and optic nerve hypoplasia * cleft palate or hare lip * meningomyelocele (a spinal defect) * omphalocele (abdominal defect) * abnormal genitalia * abnormal palm pattern * overlapping of fingers over thumb. * cutis aplasia (missing portionof the skin/hair) * prominent heel * kidney defects * deformed feet known as "rocker-bottom feet" X

16. IV. Diagnosing Gene Disorders A. Karyotype - a display of all the chromosomes in the nucleus 1. The process: • Harvested cells in metaphase are treated and stained • Chromosomes are observed under the microscope • A photograph is taken and enlarged • Chromosomes are cut out and arranged in homologous pairs • Abnormalities are identified

17. IV. Diagnosing Gene Disorders B. Prenatal Diagnosis 1. Amniocentesis • A small amount of fluid from the sac surrounding the embryo is removed • Cells from the fluid are carefully grown in the laboratory and treated with a chemical that prevents cell division • A karyotype is prepared to make certain that the chromosomes of the developing embryo are normal 2. Chroionic villus biopsy • The sample of embryonic cells comes directly from the membrane surrounding the embryo • Recent studies have linked limb defects in babies to CVB tests done before the 10th week of pregnancy.

18. V. Ethical Considerations A. Every nondisjunction occurrence greatly affects the individual’s health, life span, and/or mental capacity 1. Chromosomal disorders are easy to detect before birth 2. Parents and doctors are faced with issues that past generations NEVER had to face 3. How should a parent react to news that their child will be born with a nondisjunction condition? 4. What factors should be considered? (medical, economical, social, etc.)