Genetic disorder power point lecture by Hamid Khan

This lecture is about genetic disorder for Generic bsn and other medical science which will provide detail session on different types of genetic disease and their pathophysiology.

1. GENETIC DISORDERS
PATHOPHYSIOLOGY - II
BY: HAMID KHAN
12/6/2023 1

2. Objective

At the end of the class students will be able to:
•Differentiate between congenital and genetic disorders
•Review the basic terminologies related to genetic disorder.
•Identify the factors which cause genetic disorder.
•Discuss the chromosomal disorders with special emphasis on
aneuploidy.
•Describe the pathophysiology and clinical manifestations of :
•Trisomy 21 (Down’s syndrome)
• Monosomy X (Turner’s syndrome)
• Polysomy X (Klinefelter’s syndrome).


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3. Class Agenda
•Lecture
•Demonstration
•Question answer session
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4. Congenital disorders

Congenital defects has been described as any
structural, functional or biochemical abnormalities in
development that originate before or shortly after
birth and cause an immediate or a delayed
abnormality in the structure and function of an organ.
E.g cleft palate,cerebral palsy.

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5. Genetic Disorders


•Genetic disorders are the result of genes or
chromosomal alterations.
•It represent changes (mutations) in gene function or
changes in Chromosomal structure.

Mutation
•A mutation is a permanent change in genetic material.
Some mutations result in serious disorders.
•Single Gene disorders
•Multifactorial disorders
•Chromosomal disorders

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6. •Genetics
 Genetics is the study of heredity, the passing of
genes from parents to their offspring through the
gametes
•Genes:
Are the basic units of inheritance and they ultimately
influence all aspects of body structure and function.
•DNA
It is a long molecule that is made up of thousands
segments of genes.

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8. Chromosomes
Chromosomes are large structures made of DNA and
protein..

9. Terminologies
•GENOTYPE
•PHENOTYPE
•LOCUS
•ALLELES
•HOMOZYGOUS
•HETEROZYGOUS
•RECESSIVE
•DOMINANT

10. Genotype & Phenotype
Genotype:
The genetic make up of an individual is called genotype.
Example: Genes of a person

e.g., Blood group, eye colour, height, genetic
diseases.


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11. PHENOTYPE
The genetic make up that is expressed in a body
is called Phenotypes.
It is the physical expression of the gene.
•Example. eye color, Weight, physique.
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12. Alleles

Alternative form of a gene that code for the same
trait and are at the same location on homologous
chromosomes are called alleles. Two members of
a gene pair (gene for hair color) one inherited
from father and one from mother are called
Alleles.Eg elbino eye colour
They can be
–Homozygous
–Heterozygous


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13. A pair of homologous chromosomes (number 1) as seen at
metaphase
Locus (position of
a gene or DNA
marker)
Allele (alternative
form of a
gene/marker)

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15. Homozygous:
The person with the same alleles on
homologous chromosomes is said to be
homozygous for that trait.
Heterozygous:
The person having different alleles on
homologous chromosome is called
heterozygous for that trait.

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16. Alleles on a pair of homologous chromosome
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18. Types of Alleles
1.Dominant:
An allele that dominates or masks the
presence of another allele and are fully
expressed is said to be dominant and the trait
expressed is a dominant trait.
2.Recessive:
The alleles whose presence is completely
masked is said to be recessive and the trait is
called as recessive trait
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19. Structure of Chromosome based on
position of centromere

•Each chromosome has two arms, labeled p (the
shorter of the two) and q (the longer).
•The p arm is named for "petite" meaning
'small'; the q arm is named q simply because it
follows p in the alphabet.
•Chromosomes are connected in either
metacentric, acrocentric or telocentric manner



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20. Metacentric
•A chromosome is metacentric if its two arms are
roughly equal in length
Sub-metacentric
•If arms' lengths are unequal, the chromosome is
said to be sub-metacentric.
Acrocentric
•If the p (short) arm is so short that is hard to
observe, but still present, then the chromosome is
acrocentric.
Telocentric
•A telocentric chromosome's centromere is located
at the terminal end of the chromosome

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22. KARYOTYPE

•A karyotype is an ordered display of
chromosomes arranged according to size,
banding pattern and centromere position
•Total number is given first, followed by sex
chromosome complement & then description
of any abnormality.
•Karyotyping is done to detect chromosome
abnormalities
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23. Human Karyotype

24. Euploid
•Having a chromosome number that is an exact
multiple of the haploid number for the species
Or
•Any exact multiple of haploid number of (n=23)
chromosome is called (eu=good or true).
•Gamete (n) and normal somatic cell (2n) both
are euploid forms.

25. Aneuploidy
•Aneuploidy is an error in cell division that
results in the "daughter" cells having the
wrong number of chromosomes.
•Cause of aneuploidy is Non disjunction

26. Non disjunction
•It Occurs when either homologous chromosomes fail to
separate during anaphase 1 of meiosis, or sister
chromatids fail to separate during anaphase II.
•The result is that one gamete has 2 copies of one
chromosome and the other has no copy of that
chromosome. (The other chromosomes are distributed
normally.)
•If either of these gametes unites with another during
fertilization, the result is aneuploidy (abnormal
chromosome number)

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30. Alterations in Chromosome Number
•Aneuploidy can occur in either the sex
chromosomes or the autosomes, examples are:
•Normal number of chromosomes in human is
23pair(46)
Trisomy (47, XY +21[male]) /47, XX+21,female)
(Down’s syndrome in autosome)
Monosomy XO
(Turner’s syndrome in sex Chromosomes) ( Only Female)
Polysomy XXY
(Klinefelter,s syndrome in sex Chromosomes )( Male)

31. Monosomy
•It is a form of aneuploidy with the presence of only one
chromosome (instead of the typical two in humans) from a pair.
• Monosomy of the sex chromosome (45,X)
(2n - 1) usually lethal except for one known in humans: Turner's
syndrome (monosomy XO).
Disomy
• It is the presence of two copies of a chromosomes.
•For organisms such as humans that have two copies of each
chromosome (those that are diploid), it is the normal condition.
Trisomy (autosomal aneuploidy)
•It refers to the presence of three copies, instead of the normal two,
of a particular chromosome.
•The presence of an extra chromosome 21, which is found in Down
syndrome, is called trisomy 21.
• (both male or female child is affected) (2n +1)
•example: trisomy 21.

32. Polysomy:
•Polysomy refer to the presence of more then two copies of
chromosome.
•Example Trisomy, tetrasomy and pentasomy Tetrasomy and
pentasomy are the presence of four or five copies of a
chromosome, respectively.
•Although rarely seen with autosomes, sex chromosome
tetrasomy and pentasomy have been reported in
humans,including
•XXXX, XXXY, XXYY, XYYY, XXXXX, XXXXY, XXXYY, XXYYY and
XYYYY

33. 1.Trisomy 21 (Down’s syndrome)

•A condition in which a cell contains three
copies of chromosome # 21.
•It occurs 1/1000 live births.
•Its risk increases with maternal age.
•The basic pathology behind the syndrome is
non-disjunction

34. Trisomy 21 (Down’s Syndrome)
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37. •Mental retardation is a disability that causes
limits on intellectual abilities and adaptive
behaviors (conceptual, social, and practical
skills people use to function in everyday
lives).
•Most people with Down syndrome have IQs
that fall in the mild to moderate range of
mental retardation.
•They may have delayed language
development

38. Who is at risk for Down syndrome?
•Down syndrome increase with the age of the mother.
• Many health care providers recommend that women
over age 35 have prenatal testing for the condition.
• The risk of having baby with Down syndrome increase1
in 1,250 woman who gets pregnant at age 25, to about 1
in 100 for a woman who gets pregnant at age 40.
• Parents who have already have a baby with Down
syndrome or who have abnormalities in their own
chromosome 21 are also at higher risk for having a baby
with Down Syndrome.

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40. CLINICAL PICTURE
•Slanting almond shaped eyes
•Protruding tongue
•Small open mouth
•Single transverse crease on the palm
•Small skull
•Flat nose bridge
•Small low set ears
•Small stature and short extremities
•congenital heart disease
•Low IQ(20%-50%)

41. •Hearing problems
•Intestinal problems, such as blocked small
bowel or esophagus
•Celiac disease
•Eye problems, such as cataracts
•Thyroid dysfunctions
•Skeletal problems
•Dementia—similar to Alzheimer’s
•White spots on the iris of the eye
•Poor muscle tone, loose ligaments
•Small hands and feet

44. What other names do people use for
Down syndrome?
•In 1866 British physician, John Langdon Down,
for whom the syndrome is now named, first
described Down syndrome, as “Mongolism.”
•Down syndrome is also referred to as Trisomy
21۔

45. Sex Chromosome Aneuploidy
•A condition in which a cell contain only one
member of the chromosome pair in a diploid
cell or the presence of only one copy of a X
chromosome in a diploid cell.
•The syndrome mostly found in females 1/2500
live births.
•Normally females contain XX pair in a diploid
cell.

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46. 1.Monosomy Xo (Turner’s Syndrome)

•The term "monosomy" is used to describe the
absence of one member of a pair of
chromosomes.
• Therefore, there are 45 chromosomes in each
cell of the body instead of the usual 46.
•It's also called monosomy X,

49. Clinical Picture
•Short stature, but normal body proportions
•Widely spaced nipples
•Absence of ovaries…gonadal streaks
•No signs of secondary sex characteristics
•Edema of the hands and feet.
•Constriction of aorta
•Abnormal kidney location
•Infertile
•Normal IQ

50. (Turner’s Syndrome)

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53. 2.Polysomy X (Klinefelter Syndrome)
•Klinefelter syndrome is a genetic condition that
results when a boy is born with an extra copy of
the X chromosome.
• Klinefelter syndrome is a genetic condition
affecting males, and it often isn't diagnosed
until adulthood.
•The syndrome is always found in males

54. Klinefelter’s syndrome

55. Klinefelter’s syndrome (XXY)
•Extra copies of the sex chromosomes also
cause developmental errors, although the
effects are not fatal.
•Cases that result in an embryo with two X and
one Y chromosome (XXY) developed
Klinefelter syndrome.
•A sterile male with many female body
characteristics. and, in some cases, mental
retardation.

56. (Klinefelter’s Syndrome)
Clinical Picture
•Tall stature, but abnormal body proportion
•Later in life body looks like female
•Deficient secondary male characteristics
•High pitch feminine voice
•Thin beard
•Infertile
•Normal IQ

59. THANK YOU