The Genetic Basis of Neurological Disorders
Cora M. Turpin
1994 Woodrow Wilson Collection
The prospect of accurate predictability of human behavior through the analysis of chemical entities flies in the face of our ideals of free thought, self-determination and flexible choices. And yet, genetic research strongly suggests that some human deviant behavior may be explainable by the presence or absence of discernible genes-sequences of chemicals called "base pairs". This unit "The Genetic Basis of Neurological Disorders," describes some aspects of known genetic defects on the human neurological condition.
Family, twin and adoption studies provide convincing arguments for the importance of genetic factors in influencing and /or causing some behavioral traits. A review of basic genetic concepts is essential to glean a full understanding of these inheritance patterns. The student's vocabulary must include these concepts:
|sex chromosome||Punnett square ||crosses ||trisomy |
It may also be desirable to outline the theoretical development of Molecular Biology as follows:
Scientist / Contribution
|Delbruck|| the intellectual father of Molecular Biology|
|Bohr (physicist) || said that electrons occupy discrete energy states (orbitals) surrounding the nucleus|
|Schrdinger (physicist)|| defined electron movement within the orbitals|
|Harvey || related structure and function|
|Schleiden and Schwann || said all living things are made up of cells|
|Pauling || coded physical laws of the arrangement of atoms in a molecule|
|Bernnal || studied molecular structure using X-ray crystallography|
|Darwin and Wallace || explained heredity by population changes|
|Mendel || explained heredity in individual organisms|
|Sutton, Morgan and McClintock || explained heredity by chromosome behavior in cells|
|Beadle and Tatum || explained heredity by cellular biochemical reactions|
|Avery and Hershey || saw DNA interactions as hereditary entities|
|Watson and Crick || described the molecular structure of DNA|
|Garrod (1908) || first referred to "inborn errors" of metabolism|
These pieces of the puzzle formed the conceptual basis for the accepting of DNA molecules forming genes forming chromosomes which determine traits. Currently, two major explanations for trait inheritance are the OGOD (one gene, one disorder) theory and the QTL (quantitative trait loci ) theory which says that multiple genes cause a trait but one gene can not cause it alone. Multifactorial chromosome abnormalities are exemplary of the QTL condition; Autosomal Recessive Disorders are exemplary of the OGOD condition.
In this presentation, six categories of inheritance patterns for neurological disorders will be identified:
- autosomal recessive disorders that are caused by mistakes/mutations in the DNA of a single gene (OGOD). These traits are masked by normal genes.
- autosomal dominant disorders that are caused by mistakes/mutations in the DNA of a single gene (OGOD). These traits are NOT masked by normal genes.
- sex-linked disorders which are located on the X chromosome (OGOD).
- deletion disorders caused by the loss of base pairs.
- extra genetic material disorders caused by having more DNA than normal.
- multifactorial chromosome abnormalities caused by many genes (QTL). These common conditions have suspected inheritance susceptibility. The polygenic nature of these disorders clouds experimental results.
Many categorization schema are possible. These six were selected for convenience of reference. Some diseases have multiple inheritance patterns, e.g., hydrocephalus is inherited as an autosomal recessive, autosomal dominant, sex-linked trait or multifactorial disease: Lesch-Nyhan Syndrome is sex-linked and a deletion disease. Diseases cited in these tables are representative samples, not exhaustive listings.
AUTOSOMAL RECESSIVE DISORDERS
AUTOSOMAL DOMINANT DISORDERS
GENETIC DELETION DISORDERS
EXTRA GENETIC MATERIAL DISORDERS
MULTIFACTORIAL CHROMOSOME ABNORMALITIES
Several activities to make the study of neurological diseases more involving and less laborious are suggested here.
- Face Drawing Exercises-use descriptions of these diseases to draw the faces of affected persons. Interpret the disease symptoms columns of the included tables for characteristic head and facial features.
- a) Down's Syndrome
- b) Wilson's Disease
- c) Fragile X Syndrome
- d) Angelman Syndrome
- e) Patau Syndrome
If an abnormality is not listed, use a normal feature. A pictured chart of face/head symptoms will evolve.
FACE DRAWINGS OF SYMPTOMS
For the less imaginative classes, the teacher may draw the phenotypes on paper and have the students cut and paste from a "pool" of choices.
- The Human Neurology Disorders Learning Game. Enlarge the enclosed tables. Cut cards of poster board. Cut and paste the name of one disease or one symptom or one inheritance pattern on each card. Use the diseases with four symptoms or more. This will provide a large deck of neurological diseases and symptoms.
Card Game Rules
- Deal 8 cards to each player. (2 or more.) Place the remaining cards in the center of the table.
- The object of the game is to match as many symptoms, inheritance patterns and diseases as you can to accumulate points.
- Players may "spread" 3 or more cards that relate during his/her turn.
- Players 1) pluck, 2) spread or "hit," 3) discard. ("Hit" means to add a card to a spread already on the board.)
- Discarded cards are arranged in the order of their discard so that all can be seen. An option to plucking is to take all the cards on the discard pile-up to and including the one that can be spread. Player may keep or spread the cards he/she has gathered. When the player places the card with the disease name or its inheritance pattern on top of his pile during his /her turn, that sequence can no longer be "hit"...it is "dead". Another set of 3 related symptoms can re-open that disease.
- For beginners, use a wall chart with the information on it. For the advanced, no help should be needed.
- Points: Symptoms-5 pts. Disease name or Inheritance pattern-10 pts.
Verbal Analogies-after studying the Disorders Tables, students will try to find the relationships of concepts via verbal analogies. Samples are given below to get you started. Creative additions are great in-put from the inspired!
Which does NOT belong?
- (concept - enzyme deficiency)
- Down's Syndrome
- Gaucher Disease
- (concept - X chromosome defect)
- Myoclonic epilepsy
- Infantile bilateral striatal necroses
- (concept - irrational responses)
- Wilson Disease
- Huntingdon's Disease
- (concept - polygenetic)
- Reading Disability
- (concept - brain atrophy)
- Tourette's Syndrome
- Huntington's Disease
- (concept - late onset)
(ANSWERS: Down's, Schizophrenia, Hypertension, PKU, Tourette's Syndrome, Tay-Sachs)
- greenish iris rings: Wilson's Disease :: large testicles : ________________ (ans. Fragile X)
- sandy diapers:____________________:: red urine : Porphyria (ans. Lesch-Nyhan)
- adrenal glands: Adrenaleukodystrophy:: _________________: Hypothyrodism (ans. thyroid)
- uncontrollable laughter: Angelman :: verbal outburst :_______________(ans. Tourette's)
- 40:Huntington's :: ______: Alzheimer's (ans. 60)
- XYY:Jacob::XXY : ____________________(ans. Bar-Shever-Carr)
- QTL : _________::Dyslexia: Galactosemia (ans. OGOD)
Berkow, Robert, ed., The Merck Manual 16th Edition, Merck Research Laboratories, Rahway, N.J. 1992.
Lewis, Ricki, Case Workbook In Human Genetics, Wm. C. Brown Publishers, Dubuque, IA, 1994.
Lewis, Ricki, Human Genetics, Concepts and Applications, Wm. C. Brown Publishers, Dubuque, IA, 1994.
Magalini, Sergio, et al., Dictionary of Medical Syndromes 3rd ed., J. B. Lippincott Co., Phila., PA., 1990.
Micklos, David A. and Freyer, Greg A., "DNA Science," Cold Spring Harbor Laboratory Press, N.Y., 1990.
Plomin, Robert; Owen, Michael; McGuffin, Peter, "The Genetic Basis of Complex Human Behaviors" Science, June 17, 1994 Vol. 264 pp. 1733-1749.