A discussion on Modes of Inheritance.

1. Modes of Inheritance
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2. Your genetics load the gun. Your lifestyle
pulls the trigger – Mehmet Oz.
All diseases of Mankind except accidental
injuries have a genetic component to it.
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3. Applications:
Disease Prediction:
- Counselling for prevention.
- Early diagnosis & treatment.
- Genetic Therapy.
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4. Genetic Diseases
Single gene disorders
Mutations at specific
locus
Sickle cell anemia
Multifactorial
Disorders
Mutations at several
loci
Diabetes Mellitus
Chromosomal
disorders
Physical changes in
the chromosomes
Down’s syndrome
Mitochondrial
Disorders
Mutations in Mito
DNA
Neuropathies
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5. Gregor Johann Mendel
“The Garden Pea”
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6. Mendelian Inheritance
1. Autosomal Dominant
2. Autosomal Recessive
3. X linked Dominant
4. X linked Recessive
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7. The law of segregation
When any individual
produces gametes, the copies
of a gene separate so that each
gamete receives only one copy
(allele). A gamete will receive
one allele or the other.
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8. The Law of Independent Assortment
The alleles of different genes assort
independently of one another during gamete
formation.
Pair 1: A and a
Pair 2: B and b
Pair 3: C and c
No. of Combn. 2n
• a B C
• a B c
• a b C
• a b c
• A B C
• A B c
• A b c
• A b C
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9. Pedigree Construction
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10. 10

11. Autosomal Dominant
Most affected parents are
heterozygous.
Why?
1. Low incidence of the disease
per se (1/10,000).
2. Lethality of homozygous
individuals.
Eg: Achondroplasia,
Marfan’s syndrome.
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12. Hallmarks:
No skipping of generations - Longitudinal
Inheritance.
No sexual predilection.
Normal offspring don't transmit the disease.
Usually structural proteins are affected.
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13. Autosomal Dominant
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14. 1. Variable Expressivity.
Eg: Marfan’s syndrome.
2. Late Onset.
Eg: Huntington’s chorea.
3. High Recurrent Mutation Rate.
Eg: Achondroplasia.
4. Incomplete Penetrance.
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15. Autosomal Dominant with incomplete
penetrance
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16. Autosomal Recessive
Most affected individuals have
parents heterozygotes (Normal).
Why?
1. Low incidence of the disease
per se (1/10,000).
The likelihood of two affected
persons mating would be1/10,000
x 1/10,000 or 1/100,000,000.
Eg: Cystic fibrosis,
β- Thalassemia.
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17. Hallmarks:
No sex predilection.
Horizontal Inheritance.
Parents of affected children may be related.
The rarer the trait in the general population, the more
likely a consanguineous mating is involved.
The trait may appear as an isolated (sporadic) event in
small sibships.
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18. 18

19. 19

20. X linked disorders
X-linked genes are never passed from father to
son.
An affected female must have an affected father.
A single dose of a mutant allele will produce a
mutant phenotype in the male.(Both dom & rec.)
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21. X linked Dominant
All daughters of an affected male are affected.
All sons of an affected male and a normal female
are normal.
Males are usually more severely affected than
females.
Females are more likely to be affected than
males, even if the disease is not lethal in males.
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22. X linked Dominant
Eg:
X linked Hypophosphatasia.
Rett’s Syndrome.
Alport’s Syndrome.
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23. X linked Recessive
Males are affected. Females are carriers.
Oblique mode of transmission.
Uncle – Nephew affected.
Never occur in females except:
Turner’s syndrome.
Lyon hypothesis.
Born to affected father & carrier female.
Testicular feminisation syndrome.
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24. X linked Recessive
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25. Skipping of
generations?
Yes
Recessive
Both males and
females
involved
X linked
recessive
only males
affected
Autosomal
recessive
Dominant
Father to son?
All daughters of
father affected?
Autosomal
Dominant
X linked
Dominant
No
NoYes
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26. Mitochondrial inheritance
Maternal transmission.
The ovum -100,000 copies of mtDNA;
The sperm - <100 copies, and these are
probably lost at fertilization.
Eg: Neurological problems,
Lactic acidosis. (MELAS, Kearns Sayre
disease, LHON)
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27. 27

28. Multifactorial Disorders
Sir Francis Galton.
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29. Regression to mediocrity.
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30. Several loci are involved in the expression of the
trait.
There is no dominance or recessivity at each of
these loci.
The loci act in concert in an additive fashion,
each adding or detracting a small amount from
the phenotype.
Nature and nurture.
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31. Most affected children have normal
parents.
Applicable for traits with continuous
distribution.
Consanguinity slightly increases the risk
for an affected child.
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32. Chromosomal
Abnormalities
Numerical
abnormalities
(Aneuploidy)
Monosomy Trisomy
Structural
abnormalities
Deletion
Duplication
Translocation
Inversion
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33. Deletion Duplication Inversion33

34. Insertion
Translocation
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35. 35

36. 36

37. 37

38. 38

39. Take Home Message
Most diseases have a genetic
component to them.
Mendelian disorders are potential candidates for gene
therapy.
Lifestyle modifications have a role to play in
preventing Multifactorial diseases.
Meticulous pedigree analysis & counselling can
reduce the burden of genetic diseases in the society.
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40. References & Further Reading
Robbins & Cotran Pathological Basis of Diseases,
8th edn.
http://www.nature.com/scitable/topicpage/gregor-
mendel-and-the-principles-of-inheritance-593 -
Website of Nature Publishing Group.
http://www.uic.edu/classes/bms/bms655/index.html
- Website of Univ. of Illinois at Chicago.
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41. Thank you !
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