ahmed group lecture 27 hereditary effects of radiation lecture 27
TRANSCRIPT
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Hereditary Effects of Radiation
Lecture 27Lecture 27
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Single gene mutationSingle gene mutationChromosome aberrationsChromosome aberrationsRelative vs. absolute mutation riskRelative vs. absolute mutation riskDoubling doseDoubling doseHeritable effects in humansHeritable effects in humansRisk estimates for hereditable effectsRisk estimates for hereditable effects
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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:
MendelianChromosomalMultifactorial
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Mendelian Inheritance
Autosomal dominantAutosomal recessiveX-linked
Mendelian Diseases
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Chromosomes
Homologous
Heterologous
Homozygous
Heterozygous
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Process of DivisionSomatic Cells
Germinal Cells
Mitosis
Meiosis
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Cell Division and Chromosome Number in
Sex Cells
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Spermatogenesis
Spermatogonia
Primary spermatocytes
Secondary spermatocytes
Spermatids
Spermatozoa
Germ cell production in the male mammals
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Oogenesis
Oogonia
Primary oocyte
Secondary oocyte
Ootids
Oocyte
Germ cell production in the female mammals
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Chromosome Number
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Chromosomal aberrationsGross abnormalities either in structure or number of chromosomes such as Robertsonian translocation, monosomy, trisomy and deletion.
Multifactorial diseasesDiseases 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
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Single gene mutationSingle gene mutationChromosome aberrationsChromosome aberrationsRelative vs. absolute mutation riskRelative vs. absolute mutation riskDoubling doseDoubling doseHeritable effects in humansHeritable effects in humansRisk estimates for hereditable effectsRisk estimates for hereditable effects
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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 conclusions1. The radiosensitivity of different mutations varies by a significant factor of about 35
1. Dose rate effect was evident.Chronic dose exposure induces fewer mutationsAcute dose exposure induces more mutationThis is in contrast with Drosophila
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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.
Megamouse Project
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Single gene mutationSingle gene mutationChromosome aberrationsChromosome aberrationsRelative vs. absolute mutation riskRelative vs. absolute mutation riskDoubling doseDoubling doseHeritable effects in humansHeritable effects in humansRisk estimates for hereditable effectsRisk estimates for hereditable effects
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Doubling DoseThe 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.
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Single gene mutationSingle gene mutationChromosome aberrationsChromosome aberrationsRelative vs. absolute mutation riskRelative vs. absolute mutation riskDoubling doseDoubling doseHeritable effects in humansHeritable effects in humansRisk estimates for hereditable effectsRisk estimates for hereditable effects
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Radiation and Sex Cells
• Resistant– Post-spermatogonial cells
• Sensitive– Stem cells
• Temporary sterility– 15 rad (0.15 Gy)– 40 rad/year (0.4 Gy/yr)
• Permanent sterility– 350-600 rad (3.5 to 6 Gy)– 200 rad/yr (2 Gy/yr)No significant hormonal imbalance
• Resistant– Post-oogonial cells
• Sensitive– follicles
• Permanent sterility– 250-600 rad (2.5 to 6 Gy)– 20 rad/yr (0.2 Gy/yr)
Pronounced hormonal imbalance
Males Females
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Hereditary effects of radiation in humans
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