Download Genetic and Developmental Diseases

Genetic and
Developmental Diseases
OBJECTIVES/RATIONALE
The effects of genetic diseases have life-long consequences.
Although some genetic and developmental disorders may first
emerge at birth, these disorders may appear at any age. The
student will identify common genetic and developmental
disorders, their important signs and symptoms and common
tests used to diagnose these disorders.
I. Mitosis and Meiosis
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A. All cells of normal mature individual have
46 chromosomes.
These cells duplicate themselves and divide
to form daughter cells, each with 46
chromosomes
Process is called mitosis and can occur with
most cells in the body
I. Mitosis and Meiosis
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B. Germ cells that develop into sperm and
ova undergo a different type of cell division
called meiosis.
One chromosome from each pair is passed
on to each gamete (sperm or ovum).
Each gamete has only 23 chromosomes.
When an ovum is fertilized with a sperm, the
newly formed individual will have a combined
total of the normal forty-six chromosomes
one half (23), from each parent.
Figure 5-2: Meiosis involves two complete divisional operations forming four potential sex cells.
Comparing Mitosis & Meiosis
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Chromosome number
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Mitosis- identical daughter cells
Meiosis- daughter cells form haploids (4 cells)
Chromosome behavior
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Mitosis- act independently
Meiosis- pair together until anaphase
Genetic IdentityMitosis- identical daughter cells
Meiosis- daughter cells have new assortment of parental
chromosomes
-chromatids (either of the two daughter strands of
a replicated chromosome that are joined by a single
centromere and separate during cell division to become
individual chromosomes) are not identical (cross over)
II. Autosomal and Sex Chromosomes
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a. 44 of the 46 chromosomes determine body
function - these are referred to as autosomes
b. the remaining 2 chromosomes determine sex of
individual
XX chromosomes = female
XY chromosomes = male
It is the male sperm that determines sex of fetus
c. the sex chromosomes are in every cell of body
and are responsible for directing activity of cell
specifically for a female or for a male
Figure 5-1: Each cell nucleus throughout the body contains the genes, DNA, and
chromosomes that make up the majority of an individual’s genome.
III. Visualizing Chromosomes
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a. Karyotyping – process to visualize
chromosomes which involves:
taking picture of cell during mitosis
arranging chromosome pairs in order from largest
to smallest
numbering chromosome pairs one through 23
b. Sex chromosomes can be evaluated by a buccal
smear - test is performed by obtaining epithelial
cells from buccal cavity of mouth, staining the cell,
and microscopically observing for X chromosomes
(referred to as Barr bodies)
III. Visualizing Chromosomes
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c. Barr bodies – visualized when two X
chromosomes are present (female)
X chromosomes are much larger than Y
chromosomes and carry more genetic information.
The X chromosome carries genes for female
characteristics and other genes essential to life
(blood formation, metabolism activities,
immunization)
The Y chromosome is smaller and only carries
genes related to masculinity.
Figure 5-3: Normal human karyotype. (©Custom Medical Stock Photo.)
III. Visualizing Chromosomes
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d. chromosomes – made of units of DNA (arranged in a specific
order)
each unit of DNA is called a gene
each chromosome is made up of thousands of genes located at
precise positions in chromosome
chromosomes (one from each parent) pair up during fertilization
of egg (alleles)
this matched gene pair determines heredity (characteristics
inherited from parents)
besides facial features, hair and eye color, heredity is thought to
play a part in many other processes:
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a. development of plaque in arteries
b. obesity
c. alcoholism
d. some mental illnesses
IV. Understanding basic heredity
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A. Genotypes are the genetic pattern of an
individual.
each gene in an allele (matched pair) of genes may
be dominate or recessive.
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Dominate genotypes expressed with capital letter
(example: brown eyes = B
Recessive genotypes are expressed with smaller
(example: blue eyes = b)
if alleles in a pair match (BB or bb), they are said to be
homozygous
if alleles do not match (Bb) they are said to be
heterozygous (will only express the phenotype of
dominant gene)
IV. Understanding basic heredity
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b. expression of a trait (blue eyes, brown hair, etc.)
is called phenotype.
c. Homozygous pairs (dominant or recessive) will
always express that trait (BB = brown eyes, bb =
blue eyes, etc.)
d. Heterozygous alleles will express the phenotype
(trait) of dominate gene only. (Bb = brown eyes)
e. Heterozygous pairs are said to be carriers of
recessive disorders - recessive traits will not be
expressed unless paired with another recessive
gene
V. Abnormalities
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A. may be due to chromosomal, genetic, or
environmental factors, or combination of these
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major chromosomal abnormalities usually lead to spontaneous
abortion of fetus
chromosomal disorders are usually related to number or
placement of chromosomes
chromosomes may fail to separate properly during cell division
causing daughter cell to have an extra chromosome while
other daughter cell has no chromosomes.
Abnormal number or structure of autosomal chromosomes is
usually incompatible with life because these chromosomes
carry a large number of essential genes.
Figure 5-4: Transmission of autosomal dominant disorders. (50% chance for an affected child).
V. Abnormalities
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B. The most common autosomal chromosomal
disorder is Down syndrome (mongolism)
Also called Trisomy 21 syndrome
Caused by the presence of an extra autosome,
nondisjunction
Results in mental retardation and shorter life
expectancy
Characteristic appearance: slanted eyes, extra fold
of skin at upper medial corner of the eye, protrusion
of the tongue, short nose
Short stature, underdeveloped sex organs
Cri Du Chat Syndrome
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Cat-like cry
Caused by deletion of part of the short arm of
chromosome 5
Results in an abnormally small head with a
deficiency in cerebral brain tissue
Widely spaced eyes and mental retardation
VI. Two ways that people acquire an
abnormal gene
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A. mutation of gene during meiosis
B. passing abnormal gene from parents (heredity)
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a. genetic disorders are passed to offspring in four different ways:
autosomal dominant, autosomal recessive, sex-linked dominant, and
sex-linked recessive.
1. Autosomal dominant
Easily recognized because presence of disorders identifies
individuals with dominant gene
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Line of inheritance is easily followed from one generation to another
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Dominant genes will always be expressed
whether homozygous or hetrozygous
 Example of autosomal dominant disorder:
polydactyly (excessive number of finger or toes)
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Autosomal Dominant Diseases
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Polydactyly-is a congenital physical anomoly
causing extra fingers and toes
Achondroplasia- dwarfism
Marfan syndrome- genetic disorder of the
connective tissue; causes long fingers and
limbs; problems with heart and valves
Familial hypercholesterolemia
Figure 5-5: A 12-year old Achondroplastic dwarf. (Note the disproportion of the limbs to the
trunk, the curvature of the spine, and the prominent buttocks.)
VI. Two ways that people acquire an
abnormal gene
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2. Autosomal recessive
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Only seen when two recessive genes are paired
Each parent may be phenotypically normal or without sign of
disorder but is a heterozygous carrier of the disorder
a. When each parent is heterozygous, chance of
offspring having disorder is one in four
b. If one parent has the disorder, chances increase to
one in two
c. If one parent is homozygous dominant, none of
offspring will be affected
d. These disorders may skip generations before it is
paired with another recessive gene and is expressed
Autosomal Recessive
Figure 5-6: Transmission of recessive disorders (25% chance for an affected child).
Autosomal Recessive Diseases
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Phenylketonuria
Galactosemia
Sickle cell anemia
Tay-Sachs disease
Albinism
Cystic fibrosis
VI. Two ways that people acquire an
abnormal gene
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3. sex-linked dominant - these are more rare than recessive
disorders and are easily recognized
4. sex-linked recessive
 these disorders are typically carried by females and passed to
males
 reason for this: recessive gene disorders on the X chromosome
of female are overridden by dominance of normal gene on other
X chromosome
 in males, the X disorder is expressed because there is no
corresponding gene on the Y chromosome.
 X-linked disorders usually appear every other generation since
they are passed mother to son (mother to son; son to daughters
(who become carriers) - affected male is unable to pass this
disorder to sons because male gives a Y chromosome to sons,
not an X.
 example of sex-linked recessive disorder: hemophilia
Figure 5-8: Transmission of sex-linked disorders.
Sex-Linked Inheritance (cont.)
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Color blindness: inability to distinguish colors
Hemophilia: is a rare bleeding disorder in
which your blood doesn't clot normally;
usually passed on from mother to son
Fragile X syndrome – a break or weakness
on long arm of X chromosome
Hyperactive behavior
Large body size
Large forehead or ears with a prominent jaw
Large testicles (macro-orchidism) after the beginning of puberty
Mental retardation
Tendency to avoid eye contact
VII. Congenital anomalies
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A. Approximately two percent of all newborns
have congenital anomalies (birth defects).
a. 65% of congenital anomalies are
idiopathic (unknown cause)
b. 20% are genetic
c. 5% are chromosomal
d. 10% are environmental (maternal
radiation, infection, drugs, alcohol,
medications
Congenital Diseases
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Appear at birth or shortly after, but they are
not caused by genetic or chromosomal
abnormalities.
Congenital defects usually result from some
failure in development during the embryonic
stage, or in the first 2 months of pregnancy.
Therefore, congenital diseases cannot be
transmitted to offspring.
Ex: spina bifida, cleft lip and cleft palate, and
pyloric stenosis.
Familial Disease
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Diseases run in families but means of
inheritance are not understood
Most likely the effects of several genes
working together
Examples: diabetes, allergies, familial
polyposis
Sex Anomalies
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Turner syndrome: missing sex chromosome
Klinefelter syndrome: extra sex chromosome
Hermaphrodite: has both testes and ovaries
Pseudohermaphrodite: has either but
remainder of anatomy mixed
Figure 5-10: Karyotype for Turner syndrome (45, XO). (Catherine G. Palmer,
Indiana University)
Turner Syndrome
Figure 5-11: Karyotype for Klinefelter syndrome (47, XXY). (Catherine G. Palmer,
Indiana University)
Klinefelter Syndrome
VIII. Diagnostic Tests
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A. physical for affected individual
B. ultrasonography of fetus (determines
malformations of head, internal organs,
extremities)
C. amniocentesis (amniotic fluid analysis to
determine genetic and chromosomal
disorders after 14 wks gestation); can detect
200 various genetic diseases
D. maternal blood analysis to observe
abnormal fetal substances
Diagnosis of Genetic Diseases (cont.)
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E. Chorionic villus sampling involves
removing cells from the villi through the
cervix. Chorionic villus sampling
gives embryonic or fetal results (gender and
chromosomal information) earlier in the
pregnancy.
Genetic Counseling
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A genetic counselor usually begins with a
complete family history of both prospective
parents.
A complete, detailed family history is called a
pedigree.
Pedigrees are used to determine the pattern
of inheritance of a genetic disease within a
family.
Genetic Counseling (cont.)
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When the pedigree is complete, the genetic
counselor can inform prospective parents of
the possibility of having genetically abnormal
offspring, and they can make an informed
decision.
Gene Therapy
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A procedure that involves identification,
manipulation, and transference of genetic
segments into a host to replace defective
genes and to perform desired genetic
activities.
The genetic material used is compatible with
human DNA that may be cultured in a
microbe and delivered in a viral package or
by injection.
Also referred to as genetic engineering.
IX. Common musculoskeletal
genetic/developmental disorders
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Name: Muscular Dystrophy (MD)
Description: group of genetically inherited diseases characterized by
degeneration of muscles; most common type is Duchenne’s MD.
Etiology: genetic
Manifestations:
• onset usually between ages of two to five years
• pelvic and leg muscles usually affected first
o leads to characteristic waddling gait
o toe walking
o lordosis
o Gower’s maneuver (unusual way of getting up from squatting position
due to weakened pelvic muscles)
o bulking of muscle mass (esp. gastrocnemius) due to fat and
connective tissue deposits
M.D.
IX. Common musculoskeletal
genetic/developmental disorders
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Diagnosis:
Physical exam, muscle biopsy, electromyography
Prognosis:
• no cure for MD—physical therapy, leg braces are
effective in maintaining mobility and quality of life
• affected children usually confined to wheelchair by
age nine
• life expectancy usually in late teens or early
twenties
• death due to respiratory or cardiac complications
IX. Common musculoskeletal
genetic/developmental disorders
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Name: Congenital Hip Dislocation
Description: abnormality of hip joint resulting in femoral head slipping
out of acetabulum; more common in girls
Etiology: maternal hormones which relax mother’s pelvic ligaments
during labor, thus relaxing infant joint ligaments
Manifestations:
• asymmetrical folds of affected thigh
• difference in leg length
• limited abduction of affected leg
Diagnosis: physical examination and hip joint X-ray
Treatment:
• closed reduction (placing femoral head in acetabulum); and
maintaining normal position by use of cast for approximately two to
three months
• surgical treatment may be required in older children
Congenital Hip Dislocation