Download Congenital And Genetic Disorders

Congenital and Genetic
Disorders
BIO 375
Pathophysiology
Review of Genetic Control
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Genetic information for each cell is
stored on chromosomes:
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Each body cell contains 2 sets (diploid) of
chromosomes; one inherited from each
parent
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22 pairs of autosomes
1 pair of sex chromosomes (XX or XY)
Karyotype is an arrangement of a cell’s
chromosomes based on size and shape
Meiosis reduces the diploid number to
haploid (1 set of autosomes + X or Y)
Human Karyotype
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Meiosis and Fertilization
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Meiosis reduced the 2n chromosome number
or 46 down to n chromosome number of 23.
Each ovum (egg) and sperm have 23
chromosomes
All eggs have an X sex chromosome
Sperm are either X or Y
Fertilization of an egg by sperm reestablishes
the diploid number of 46 and XX (female) or
XY (male) sex determination.
Chromosomes and Genes
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Each chromosome contains many genes
which code for traits like hair color or
metabolic enzymes.
Genes are arranged in a linear fashion
Humans have about 22,000 genes
Each gene may exist in a population in
alternative forms called alleles
Some alleles code for faulty or disease
causing genes
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Some Terminology
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Dominant vs. recessive
Genotype vs. phenotype
Homozygous vs. heterozygous
Codominance
Incomplete dominance
Multiple alleles
Autosomal vs. sex linked inheritance
Sex influenced vs. sex linked
Polygenic (metric) traits
More Terminology
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Penetrance
Expressivity
Carrier
Age of onset
Teratogenic agents
Developmental
disorders
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DNA replication and Mutations
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DNA is copied from generation to
generation by a process called semiconservative replication
This is a highly accurate process
Even so, occasionally, a copy error
occurs resulting in a mutation
Mutations can arise by other processes
DNA “code” is transcribed to RNA and
then translated into protein structures
Gene Inheritance
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Genes control:
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Physical structures, e.g. collagen
Metabolic processes, via enzymes
Patterns of behavior, e.g. schizophrenia
Both normal and disease causing genes are
inherited in predictable patterns
Genetic disorders may be:
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Single gene traits
Multiple gene traits
Due to chromosomal defects (number or structure)
Examples of Gene Inheritance
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Autosomal single gene disorder:
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Sex linked single gene disorder
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Multiple alleles
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Polygenic trait
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Age of onset
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PTC taster or cystic fibrosis
Red-green colorblindness or hemophilia
ABO blood types
Intelligence or schizophrenia
Tay-Sachs disease
Huntington’s disease
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Sex influenced trait
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Pattern baldness
Baldness dominant in
male heterozygote
but recessive in
female heterozygote
Lyon Hypothesis (1961)
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Named after Mary Frances Lyon
Suggested that dosage compensation
in mammals is by inactivation of all but
one X chromosome in cells with more
than one X chromosome.
Inactivation occurs at about day 16.
The Barr body, visible in some female
mammalian cells, is an inactivated X
chromosome (Murray Barr 1949)
Consequences of X-inactivation
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Multisomies are more tolerated in the Xchromosomes than autosomes
Dosage compensation
Variable expression in heterozygous
females, e.g. hemophilia A
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Chromosomal number defect
Kleinfelter’s Syndrome
XXY 1/1,000 male births
Turner’s Syndrome
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Turner’s Syndrome XO (1 in
10,000 female births)
Monosomy of sex
chromosomes; Almost normal
in appearance until puberty
Fail to menstruate; secondary
sex characteristics fail to
develop
Shield chest; webbed neck;
short stature
Down’s Syndrome
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Down’s Syndrome Trisomy
21 (1 in 600 births)
Epicanthal eye folds;
hypotonia of skeletal
muscles; small mouth with
tongue protrusion
common
Atypical palm creases;
pubic hair and beards
sparse in males; heart
malformations and low
resistance to disease
common
Males infertile; some
females fertile; low IQ
scores
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Chromosomal
structure defect
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Cri du chat syndrome
(cat cry syndrome)
deletion of part of
short arm of
chromosome 5
Developmental Disorders
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May be due to exposure of embryo to
negative environmental influences
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Radiation
Alcohol (fetal alcohol syndrome)
Cigarette smoking (low birth weight)
Drugs
Cocaine
Abuse
Maternal infections (e.g. Rubella)
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Exposure in first two weeks usually
results in death of embryo
First two months most critical
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Time of rapid cell division
Time of organogenesis
There are different critical periods for
different systems
Developmental Disorders
Diagnostic tools
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Pedigree analysis, e.g. in
families where inherited
disorders are present
Screening for carriers,
e.g. Tay-Sachs
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Diagnostic tools
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Amniocentesis, e.g.
chromosomal
disorders and come
gene defects
Neonatal testing, e.g.
phenylketonuria
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