Transcript Hereditary effects of radiation

Lecture 27
Hereditary Effects of Radiation
Lecture 27
Ahmed Group
Single gene mutation
Chromosome aberrations
Relative vs. absolute mutation risk
Doubling dose
Heritable effects in humans
Risk estimates for hereditable effects
Lecture 27
Ahmed Group
Genetic diseases are attributed to mutations
occurring in germ cells and are transmitted to
progeny (hereditary diseases).
Spontaneous mutation rates are increased by radiation
exposure
Three principal categories of genetic diseases:
Mendelian
Chromosomal
Multifactorial
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Mendelian Inheritance
Mendelian Diseases
Autosomal dominant
Autosomal recessive
X-linked
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Chromosomes
Homologous
Heterologous
Homozygous
Heterozygous
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Somatic Cells
Process of Division
Mitosis
Germinal Cells
Meiosis
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Cell Division and Chromosome
Number in Sex Cells
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Germ cell production in the male mammals
Spermatogenesis
Spermatogonia
Primary spermatocytes
Secondary
spermatocytes
Spermatids
Spermatozoa
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Germ cell production in the female mammals
Oogenesis
Oogonia
Primary oocyte
Secondary oocyte
Ootids
Oocyte
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Chromosome Number
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Chromosomal aberrations
Gross abnormalities either in structure or number of
chromosomes such as Robertsonian translocation, monosomy,
trisomy and deletion.
Multifactorial diseases
Diseases known to have genetic component but also
environmental factors:
-Known to have a genetic component
-Transmission pattern not simple Mendelian
-Congenital abnormalities: cleft lip with or without cleft palate;
neural tube defects
-Adult onset: diabetes, essential hypertension, coronary heart
disease
-Interaction with environmental factors
Lecture 27
Ahmed Group
Lecture 27
Ahmed Group
Lecture 27
Ahmed Group
Single gene mutation
Chromosome aberrations
Relative vs. absolute mutation risk
Doubling dose
Heritable effects in humans
Risk estimates for hereditable effects
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Ahmed Group
Radiation induced hereditary effects
Children of Japanese survivors of atomic bomb
attacks on Hiroshima and Nagasaki.
Relative versus direct mutation risk
“If nature can do it, radiation can do it”.
In a set of genes:
Av of spontaneous mutation rate
Relative mutation risk =
Av of radiation-induced mutation rate
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Megamouse Project
7 million mice were used
Five major conclusions
1. The radiosensitivity of different mutations varies by a
significant factor of about 35
1. Dose rate effect was evident.
Chronic dose exposure induces fewer mutations
Acute dose exposure induces more mutation
This is in contrast with Drosophila
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Lecture 27
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Megamouse Project
Five major conclusions continued
3. The male is more radiosensitive than females.
4. The genetic effects of a given radiation dose can be
reduced greatly if a time interval is allowed
between exposure and conception.
5. The estimate of the doubling dose adopted by BEIR
V and UNSCEAR 88 is 1 Gy.
Lecture 27
Ahmed Group
Single gene mutation
Chromosome aberrations
Relative vs. absolute mutation risk
Doubling dose
Heritable effects in humans
Risk estimates for hereditable effects
Lecture 27
Ahmed Group
Doubling Dose
The doubling dose is the dose required to double the spontaneous mutation rate.
• A low doubling dose (5-150 R) for
mutations was estimated from fruit fly
experiments.
• Hereditary effects are cumulative.
• Excess incidence of leukemia was evident
but much larger number of solid tumors did
not appear until many years later in
Japanese survivors of the A-bomb attack.
Lecture 27
Ahmed Group
Single gene mutation
Chromosome aberrations
Relative vs. absolute mutation risk
Doubling dose
Heritable effects in humans
Risk estimates for hereditable effects
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Ahmed Group
Radiation and Sex Cells
Males
• Resistant
– Post-spermatogonial cells
• Sensitive
– Stem cells
• Temporary sterility
– 15 rad (0.15 Gy)
– 40 rad/year (0.4 Gy/yr)
Females
• Resistant
– Post-oogonial cells
• Sensitive
– follicles
• Permanent sterility
– 250-600 rad (2.5 to 6 Gy)
– 20 rad/yr (0.2 Gy/yr)
• Permanent sterility
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– 350-600 rad (3.5 to 6 Gy)
– 200 rad/yr (2 Gy/yr)
No significant hormonal
imbalance
Pronounced hormonal
imbalance
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Hereditary effects of radiation in humans
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Ahmed Group
Lecture 27
Ahmed Group