Chapter 4
Down Syndrome is caused by abnormalities in trisomy 21. Aneuploidy. 3 copies of one
cell (trisomy).
Cystic fibrosis is caused by autosomal recessive genes. Mutations in the CFTR gene,
which is supposed to code for a Chloride ion channel.
- 2 conditions with each below
Autosomal recessive: Cystic fibrosis, PKU, Sickle cell, Tay-Sachs, hemochromatosis
and galactosemia
Autosomal dominant: Huntington’s, Retinoblastoma
Sex-linked recessive: X linked recessive: DMD, Hem A, male baldness, Becker muscular
Sex linked Dominant: Fragile X syndrome, Alport syndrome, Rett syndrome
Transcription: RNA is synthesized from a DNA template. Begins with RNA polymerase.
Nondisjunction: an error in which homologous chromosomes or sister chromatids
fail to separate normally during meiosis or mitosis.
Aneuploidy: A cell that does not contain multiple of 23 chromosomes.
Polyploidy: Euploid cells (normal # of chromosomes) has more than the diploid
number of chromosomes.
Translocation: The interchange of genetic material between nonhomologous
chromosomes.
Penetrance: The percentage of individuals with a specific genotype who also exhibit
the expected genotype.
Expressivity: Extent of variation in phenotype associated with a particular genotype.
The severity varies from person to person.
Dominance: The allele whose effects are observable
Recessiveness: The allele whose effects are hidden.
Blood type inheritance: from parents to offspring but based on the parents' alleles.
How is a recessive disease inherited: Both parents are heterozygous (Bb), one-fourth
of their offspring will be normal (BB), half would be heterozygotes (Bb) and
one-fourth homozygotes with the disease (bb). Risk is 25% unless both parents are
homozygous, then 100%.
Inheritance of Hemophilia A: Results from expressivity. A mutation that alters only
one amino acid of the factor VIII gene produces a mild form of Hemophilia A, a
“stop” codon usually produces a more severe form of Hem A
Mental retardation cause: Deletion or duplication of genes/chromosomes.
Neurofibromatosis
- Type 1: Von Recklinghausen. The most prevalent form. Neurofibromin 1 is a
gene that encodes the protein neurofibromin, a tumor suppressor (prevents
cells from growing and dividing too quickly), primarily in adult neurons.
Mutations of NF1 cause multiple cutaneous neurofibromas, cutaneous light
brown macular lesions (cafe au lait spots and freckles). Gliomas may develop
bone and soft tissue tumors. Inactivation of the NF! Gene results in loss of f(x)
of neurofibromin in Schwann cells (produce the myelin sheath around axons)
and promotes tumorigenesis (neurofibromas). Cognitive and learning
disabilities are present in 50% of affected individuals.
- Type 2: Neurofibromatosis type 2. NF2 is rare. Normally Neurofibromin 2 is A
tumor suppressor protein that inhibits cell growth. Mutations promote dvmt of
CNS tumors, schwannomas, but other tumors like meningiomas, ependymomas,
astrocytomas and neurofibromas may occur. Cutaneous signs of flesh colored
skin flaps and muscle wasting occur. People with NF2 have extensive morbidity
and reduced life expectancy.
- Type 3: Schwannomatosis. Very rare. It’s characterized by multiple
schwannomas in the absence of bilateral vestibular schwannomas. Primary
symptom is chronic pain.
- Diagnosis is based on symptoms. Surgery is major txmt, tumors may regrow.
Targeted therapy. Genetically tailored drugs are used to provide personalized
therapy.
Klinefelter Syndrome characteristics: Small testes, some breast dvmt, sparse body
hair, and long limbs. Presence of 2 or more X chromosomes with 1 Y chromosome.
High pitched voice.
Turner syndrome characteristics: Missing sex chromosome; Short stature, female
genitalia, webbed neck, shield-like chest with underdeveloped breasts and widely
spaced nipples, and imperfectly developed ovaries.
Cri du chat syndrome characteristics: Cry of the cat. Caused by deletion of a region
of chromosome 5. Other s/s include low birth weight, severe intellectual disability,
microcephaly (small head size), and heart defects.
Gene therapy can be applied in two ways. Somatic cell therapy consists of inserting
normal genes into the cells of an individual who has genetic disease to treat
abnormal RBC production.
In DNA replication, The DNA polymerase enzyme travels along a single DNA strand,
adding correct nucleotides to the free end of the new strand.
Transcription is the process by which RNA is synthesized from a DNA template.
Geimsa staining technique is used so that chromosomes can be unambiguously
numbered and individual variation in chromosome composition. Missing or
duplicated portions of chromosomes can also be identified bc of banding techniques.
Neural tube defects cause an elevation of alpha fetoprotein in the amniotic fluid and
hundreds of diseases caused by mutations of single genes.
Amniocentesis is recommended for pregnancies that have an elevated risk for a
genetic disease or in women older than 30-35 years old.
Chorionic villus sampling consists of extracting a small amount of villous tissue from
chiron. This procedure allows for prenatal diagnosis of chromosomal abnormalities
at 3 months’ gestation.
Aneuploidy is usually the result of nondisjunction, an error in which homologous
chromosomes or sister chromatids fail to separate normally during meiosis or
mitosis.
Individuals with Trisomy 21 present with an IG of 25-70, low nasal bridges, protruding
tongue, flat, low-set ears and epicanthal folds (produces an asian appearance).
Nondisjunction during formation of one of the parent’s gametes or during early
embryonic development occurs in formation of mother’s egg cells. Maternal
nondisjunction.
Turner’s syndrome a sex chromosome is missing and the person's total chromosome
count is 45. It presents as short stature, female genitalia, webbed neck, shield-like
chest with underdeveloped breasts and widely spaced nipples and imperfectly
developed ovaries.
A disorder in chromosome (47, XXY karyotype) results in Klinefelter syndrome.
Resulting from nondisjunction of the X chromosomes in the mother.
Fragile X syndrome is second most commonly recognized cause of mental retardation
after Down syndrome
In blood type, having A and B alleles as codominant create AB blood type.
Affected heterozygous individuals transmit traits to one half of their kids. It’s
possible that all or none of their kids may have the trait.
When a child inherits a disease that's autosomal recessive, it's inherited from both
parents.
Expressivity is the extent of variation in phenotype associated with a particular trait.
Retinoblastoma has been mapped to the long arm of chromosome 13. This is the
tumor suppressor gene.
CF is a lethal autosomal recessive disease.
Consanguinity is an important characteristic of pedigrees for recessive diseases.
Relatives share a certain proportion of genes received from a common ancestor.
Consanguinity refers to the mating of two related individuals and the offspring of
such matings are said to be inbreds. “Family relations”
Males, having only one X chromosome (normal), are said to be hemizygous for genes
on this chromosome.
Males are more frequently affected by X-linked recessive diseases, with the difference
becoming more pronounced as the disease becomes rarer. Sex-linked recessive.
Skipped generations are often observed in X-linked recessive disease pedigrees
because the gene can be transmitted through female carriers.
Cri du chat, cry of the cat, describes a characteristic cry of an affected child.
X linked recessive conditions are passed from an affected father to all of his
daughters who transmit it to ½ of their sons.
DNA is formed and replicated only in the cell's nucleus.
Recurrence risk of autosomal dominant diseases is usually 50%.
An individual’s genotype is his or her genetic makeup.
Becker muscular dystrophy and Duchenne muscular dystrophy are X-linked recessive.
Consistent pairing of adenine with thymine and guanine with cytosine is
complementary base pairing and the key to DNA replication.
Chromosome abnormalities are the leading cause of mental retardation and
miscarriage.
Prenatal testing is conducted before or during pregnancy. Testing includes
amniocentesis, Chorionic villus sampling (CVG) and Preimplantation genetic
diagnosis (PGD).
The complete human genome sequence will facilitate gene identification, diagnosis
and appropriate disease treatment.
CF is autosomal recessive
DMD is X-linked recessive
Sickle cell disease is autosomal recessive
Huntington's disease is autosomal dominant.