Medicine

1. By silas mkombe
GENETIC BASIS OF
DISEASE

2. OBJECTIVES
At the end of the lesson the learner should be
able to:
 Define terminologies
 Describe the mechanisms of genetic disease
development
 Explain the inheritance patterns in genetic
diseases
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3. Cont.
 Genetics is the scientific study of heredity, which is the
passing of characteristics from parents to their offspring.
 Heredity determines the general shape of the body but body
weight depends on the kinds of food one takes.
 The cell is the fundamental structural and functional unit of
an organism.
 The study of cells has shown that characteristics of an
organism are usually transmitted to its offspring through
particles called genes.
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4. cont.
 Molecular genetics is the study of chemical basis of heredity.
 This concludes that offspring inherit characteristics of their parents
through information contained in definite structures called genes,
which are located on the chromosomes.
 This important genetic information is required for the life of the cell
and for the ability of the cell to perform its functions in the body.
 It is therefore prudent to infer that genes are units of instruction
located on chromosomes and produces or influence a specific trait
in the offspring.
 The passing of traits from parents to the offspring is called heredity.
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5. Cont.
 Genes are structures located on the chromosomes in cell and
carry information or instructions for all the operations of the
cells.
 A gene is part of a cell that determines the characteristics
living things inherit from their parents e.g. sex, height, hair
color etc.
 Every cell has thousands of genes, which produce their
effects by influencing chemical and physical processes of the
cell during growth and aging.
 Genes cannot be seen by simple light microscopy.
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6. Terminologies.
 Alleles – two or more alternate forms of a gene. Allele – short
form of allelomorph “a Greek word – “allele” meaning “each
other “and morphe – “form”
 Chromosome– is a threadlike structure found in cells of all
Organisms and is made up of DNA and proteins.
 Dominant genes – genes that determine the expression of
the genetic trait in offspring.
 Gene – units of instruction, located on chromosomes
 Genotype – refers to the genes an organism contains
 Heredity – is the passing of traits from parents to offspring
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7. Cont.
 Heterozygous – genotype in which the gene pairs are
different
 Homozygous – a genotype in which the gene pairs are
identical
 Phenotype – the observable traits of an organism that arise
because of the Interaction between genes and the
environment
 Recessive genes – genes overruled by dominant genes that
determine the genetic trait
 Gene mapping – method of locating and identifying genes on
chromosomes
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8. Cont.
 Gene therapy – technique for treating diseases
by providing cells of a patient’s body with a
normal gene to make up for a defective or
missing gene.
 Genetic variation – the difference in inherited
traits that exist among members of a species.
 Mutation – chemical change in gene.
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9. Intro.
 Living matter or organisms have a
reproductive capacity and ability to adapt to
changing circumstances.
 They have the ability to adjust any damage,
which may be sustained during injury
produced and is within the acceptable limits.
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10. Cont.
 Pathological lesions are built through mechanisms
that involve the variations in structural and
chemical components of the cells as a result of
the body’s normal response to abnormal
environmental influences such as trauma and
pathogenic organisms.
 Disease may also be as a result of inherited
defects acting singly or in combination with
environmental factors.
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11. Cont.
 The genetic or cytogenetic defects are usually present at birth
(congenital) but their features are seen at various ages and
stages of development but most of them are obvious during
infancy.
 Genetic diseases can be due to an alteration in one gene,
several genes in combination with environmental factors or
due to imbalance of many genes.
 These are the basis of the three main classes of genetic
disorders:
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12. Cont.
1. single-gene disorders — mutations in single
genes often causing loss of function,
2. multifactorial conditions — variants in genes
interacting with the environment and causing
alteration of function, and
3. chromosomal disorders — causing chromosomal
imbalance and alteration in gene dosage.
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13. MENDEL AND LAWS OF
HEREDITARY
Introduction
 Gregor Mendel did carry out many experiments to
determine transmissions of various characteristics
from parent garden peas to the offsprings in order to
explain the concept of inheritance.
 He observed characteristics such as size (tall stem
and short stem), flowers (red and white) and seeds
(smooth and wrinkled).
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14. Cont.
 It was observed that genes controlling a characteristic
of an organism exist in two varieties of dominant or
recessive.
 These different forms of a gene are called alleles.
Alleles or allelic genes are different versions of one
another.
 For example in the experiment on genes controlling
the size of the pea, one gene (T) resulted in tall plant (
the dominant gene) and the other gene (t) produce a
dwarf plant only when two of them (tt) were present
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15. Cont.
 When an organism contains identical alleles it is said
to be homozygous (can be homozygous dominant),
TT or homozygous recessive, tt) and if it contains two
distinct alleles it is heterozygous
 The genetic constitution of an organisms known as its
genotype while its phenotype refers to the way the
genes express themselves in the structures of the
organism to produce the outward appearance of the
organism.
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16. Cont.
 Example: Punnett square for the experiment
on size of garden pea.
 A Punett square is a chart used to show the
possible combinations of alleles in offsprings.
Female gametes
Male gametes
T T
T TT Tt
t tT Tt
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17. Mendel’s First law: The law of segregation
 An organism’s characteristics are determined by
internal factors, which occur in pairs only one
member of the pair can be carried on a single
gamete.
 Example in meiosis where there is separation of
paired genes.
 This explains the inherence in human that results
in production of hybrids.
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18. Cont.
 A hybrid is an offspring that differs from the
parents in one or more traits.
Monohybrid inheritance
 Monohybrid inheritance is transmission of only
one pair of contrasting characteristic e.g
albinism
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19. Cont.
Example
 Albinism results from homozygous recessive state
(aa) because the normal skin has homozygous AA
or heterozygous Aa.
 a phenotypic ally normal couple gets an albino
child.
 This means that parents are carries who possess
the recessive gen. the genotype this couple is Aa.
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20. Cont.
The probability that the couple will have an albino
child ¼ a normal child (both genotype and
phenotypel is ¼.
Dihybrid inheritance
 Dihybrid inheritance involves inheritance of two
pairs of characteristics for instance the cross
breeding of tall colored garden peas with dwarf
whites ones.
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21. Cont.
Male gametes
Female
gametes
TC Tc tC tc
TC TTCC TTCc TtCC TtCc
Tc TTcC TTcc TtcC Ttcc
tC TtCC TtCc ttCC ttCc
tc tTcC tTcc ttcC ttcc
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22. Cont.
 The probability of getting tall colored is 9/16, tall
white 3/16, dwarf colored 3/16 and dwarf while is
1/16.
 There are instance when more than two
characteristics have to be transmitted e.g. Rhesus
factor in blood grouping that depends on alleles
CDE and cde.
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23. Mendel’s Second law: The law of independent
Assortment
 Each of the two alleles of one gene may
combine with either of the alleles of another
gene.
 This brings in the concept of probability in that
transmission of genes occurs as independent
events with different chance of fusion
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24. Cont.
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25. Cont.
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26. CAUSES OF GENETIC
DISEASES
 Genetic disorders are caused by permanent
alterations or mutations of the individual's DNA.
 Mutations can affect the entire genome,
chromosomes, genes or regulatory elements of
genes.
 Genes contain the instructions on how to make
proteins
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27. Cont.
 An altered DNA sequence in a gene causes a
change in the protein sequence, potentially
resulting in loss of function.
 Proteins carry out many different functions in
the body, and mutations in virtually every
functional class of proteins can cause genetic
disease.
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28. Cont.
Genetic disorders can be inherited or acquired
through
 Mutations
 Inherited Mutations - mutations passed down through
families.
 Acquired Mutations - in some cases, genetic diseases
may be caused by acquired mutations.
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29. Cont.
Such is the case for many forms cancer, the most
common genetic disease, according to The Human
Genome.
 Spontaneous Chromosomal Abnormalities - some
children may develop genetic diseases that are not
inherited, but occur as a result of spontaneous genetic
abnormalities found in the egg or sperm during
conception.
 Environmental factors
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30. Mechanisms of Genetic Disease
 Single gene disorders are caused by
mutations of a single gene and follow specific
inheritance patterns.
 Examples are Marfan’s syndrome, cystic
fibrosis and sickle cell anaemia.
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31. Cont.
 Multifactorial disorders include some of the most
common chronic diseases, such as heart disease,
diabetes and cancer, and are caused by a
combination of genetic and life-style factors.
 Chromosomal disorders are caused by changes in
the number or structure of chromosomes, as seen
in Down or Turner syndrome.
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32. CLASSIFICATION OF GENETIC
DISORDERS
1. Mendelian (Single Gene) disorders
a) Autosommal Disorders
Autosommal dominant disorders
Autosommal recessive disorders
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33. Cont.
b) Sex (X-linked) disorders
X-linked dominant disorders
X-linked recessive disorders
Y-linked disorders
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34. Cont.
2. Chromosomal (Cytogenic) disorders
a) Numerical abnormalities
a) Polyploidy
b) Aneuploidy
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35. Cont.
b) Structural abnormalities
a) Translocations
b) Deletions
c) Inversions
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36. Cont.
3. Metabolic (In borne errors) disorders
4. Somatic cell disorders
5. Multifactorial disorders
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37. U cant run away from who u
are.
THANK YOU
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