Genetic and Developmental Diseases OBJECTIVES/RATIONALE The effects of genetic diseases have...
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![Page 1: Genetic and Developmental Diseases OBJECTIVES/RATIONALE The effects of genetic diseases have life-long consequences. Although some genetic and developmental.](https://reader035.fdocuments.us/reader035/viewer/2022062421/56649d875503460f94a6c17c/html5/thumbnails/1.jpg)
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.
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I. Mitosis and Meiosis
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
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I. Mitosis and Meiosis
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.
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Figure 5-2: Meiosis involves two complete divisional operations forming four potential sex cells.
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Comparing Mitosis & Meiosis Chromosome number-
Mitosis- identical daughter cells Meiosis- daughter cells form haploids (4 cells)
Chromosome behavior- Mitosis- act independently Meiosis- pair together until anaphase
Genetic Identity-Mitosis- identical daughter cellsMeiosis- 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)
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II. Autosomal and Sex Chromosomes 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
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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.
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III. Visualizing Chromosomes
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)
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III. Visualizing Chromosomes
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.
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Figure 5-3: Normal human karyotype. (©Custom Medical Stock Photo.)
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III. Visualizing Chromosomes
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: a. development of plaque in arteries b. obesity c. alcoholism d. some mental illnesses
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IV. Understanding basic heredity A. Genotypes are the genetic pattern of an
individual. each gene in an allele (matched pair) of genes may
be dominate or recessive. 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)
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IV. Understanding basic heredity 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
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V. Abnormalities
A. may be due to chromosomal, genetic, or environmental factors, or combination of these 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.
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Figure 5-4: Transmission of autosomal dominant disorders. (50% chance for an affected child).
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V. Abnormalities 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
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Cri Du Chat Syndrome
• 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
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VI. Two ways that people acquire an abnormal gene A. mutation of gene during meiosis B. passing abnormal gene from parents (heredity)
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 Line of inheritance is easily followed from one generation to another 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• 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
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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.)
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VI. Two ways that people acquire an abnormal gene 2. Autosomal recessive
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
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Autosomal Recessive
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Figure 5-6: Transmission of recessive disorders (25% chance for an affected child).
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Autosomal Recessive Diseases• Phenylketonuria• Galactosemia• Sickle cell anemia• Tay-Sachs disease• Albinism• Cystic fibrosis
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VI. Two ways that people acquire an abnormal gene 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
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Figure 5-8: Transmission of sex-linked disorders.
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Sex-Linked Inheritance (cont.)• 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
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VII. Congenital anomalies
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
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Congenital Diseases 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.
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Familial Disease
• 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
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Sex Anomalies
• Turner syndrome: missing sex chromosome• Klinefelter syndrome: extra sex chromosome• Hermaphrodite: has both testes and ovaries• Pseudohermaphrodite: has either but
remainder of anatomy mixed
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Figure 5-10: Karyotype for Turner syndrome (45, XO). (Catherine G. Palmer, Indiana University)
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Turner Syndrome
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Figure 5-11: Karyotype for Klinefelter syndrome (47, XXY). (Catherine G. Palmer, Indiana University)
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Klinefelter Syndrome
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VIII. Diagnostic Tests
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
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Diagnosis of Genetic Diseases (cont.) 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.
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Genetic Counseling
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.
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Genetic Counseling (cont.)
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.
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Gene Therapy 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.
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IX. Common musculoskeletal genetic/developmental disorders 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
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M.D.
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IX. Common musculoskeletal genetic/developmental disorders 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
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IX. Common musculoskeletal genetic/developmental disorders 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
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Congenital Hip Dislocation