Transcript 22.0GeneticDisorders

Genetic
Disorders
Things Can Go Wrong
With DNA and/or Chromosomes
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!
One nucleotide
Nucleotide
Structure
DNA Structure
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
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
II. DNA Based Disorders
Normal
Red Blood
Cell
Sickle Cell
2. 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
III. Chromosomal Based Disorders
A.
Causes
1. Nondisjunction
• during meiosis I, homologous chromosomes do not
separate properly
• Results in an extra copy of a chromosome in one
cell, and a loss of that chromosome from another
III. Chromosomal Based Disorders
B.
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
III. Chromosomal Based Disorders
C.
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
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
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 chest
low set ears, webbed neck
• no mental deficiencies
III. Chromosomal Based Disorders
E. Nondisjunction of Autosomal (non-sex) Chromosomes
• Can affect chromosomes #1 - #22
•
•
There are only 3 trisomes 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.
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.
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.
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 portion of the skin/hair)
* prominent heel
* kidney defects
* deformed feet known as "rocker-bottom feet"
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
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.
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.)