This document provides information on genetics and genetic diseases: - It defines genetics as the study of heredity and variation of inherited traits. Key concepts discussed include genes, alleles, nucleotides, codons, and the genetic code. - It describes different types of genetic diseases including single gene defects, multifactorial diseases, and cytogenetic disorders caused by chromosome abnormalities. - Causes of genetic mutations are explained, including point mutations, frameshift mutations, and trinucleotide repeat expansions. Methods of diagnosis such as karyotyping, FISH, and molecular analysis are also summarized.

2. • The branch of biology that deals with heredity, especially
the mechanisms of hereditary transmission and the
variation of inherited
characteristics among
similar or related
organisms

3. • Gene
• Alleles - Dominant
- Recessive
• Nucleotides
• Codon
• Genetic Code

4. • Biological unit of heredity.
• Gene hold the information to build and maintain their
cells and pass genetic traits to offsprings
• In cells, a gene is portion of
DNA

5. Gene (DNA)
RNA formation
Protein formation
Cell structure Cell enzymes
Cell function

6. • Is one member of a pair or series of different forms of a
gene.
• Homozygous-an organism in which 2 copies of genes are
identical i.e. have same alleles
• Heterozygous-an organism which has different alleles of
the gene

8. • Chromatin: DNA, RNA &
proteins that make up
chromosme
• Chromatids: one of the two
identical parts of the
chromosome.
• Centromere: the point where
two chromatids attach
• 46 chromosomes. 22 pairs
Autosomes and 1 pair Sex
chromosomes.

9. • NUCLEOTIDE: group of molecules that when linked
together, form the building blocks of DNA and RNA;
composed of phosphate group, the
bases:adenosine,cytosine,guanine and thymine and a
pentose sugar.In case of RNA,thymine base is replaced
by uracil.
• CODON: series of three adjacent bases in one
polynucleotide chain of a DNA or RNA molecule which
codes for a specific amino acid.
• GENETIC CODE: the sequence of nucleotides in a DNA
or RNA molecule that determines the amino acid
sequence in the synthesis of proteins.

10. • Congential Disease.
Diseases which are present at birth.
• Hereditary/Familial Disease.
Diseases which are derived from one’s parents
and trasmitted in the gametes through the generations.
Not all congenital diseases are genetic( congenital
Syphilis) and not all genetic diseases are congenital
(Huntington disease).

12. •Definition:
Permanent changes in the
DNA. Those that affect germ cells are
transmitted to the progeny. Mutations
in the somatic cells are not transferred
to the progeny but are important in the
causation of cancer and some
congenital diseases.

13. Nitrous acid
Alkylating agents
5- bromouracil
Antiviral drug iododeoxy uridine
Benzpyrene in tobacco smoke
X – rays & ultraviolet light
Certain viruses such as bacterial virus
Chemicals

15. •
Point Mutation:
Substitution of a single
nucleotide base by a
different base.
• Categorized as:
• Transition
• transversion
• MissenseMutations
• NonsenseMutations

16. • Frameshift
Mutations:
Insertion or
deletion of one or
two base pairs
alters the reading
frame of the DNA
strand.

17. Trinucleotide
Repeat
Mutations:
set of genetic
disorder
caused by
trinucleotide
repeat in
certain genes
exceeding
normal,stable
threshold e.g.
Fragile X
Syndrome.

18. • Single Gene Defects/Mendelian Disorders.
• Disorders with Multifactorial or Polygenic inheritance.
• Cytogenetic Disorders.
• Disorders showing atypical patterns of inheritance.

19. A genetic disease caused
by a single mutation in the
structure of DNA, which
causes a single basic
defect with pathologic
consequences

20. • Autosomal Dominant
• Autosomal Recessive
• X-Linked Recessive
• X-Linked Dominant

22. • Manifested in heterozygous states.
• Individuals with these diseases usually have
one affected parent .*
• Variable to late onset.
• These disorders usually involve non-enzymatic
proteins;
• Proteins involved in metabolic pathway
regulation.
• Structural Proteins.

23. • Typical mating pattern
is a heterozygous
affectedindividual with
a homozygous
unaffectedindividual.
• Every child has one
chance in two of having
the disease
• Both sexes are
affected equally..

25. • Marfan’s Syndrome.
• Ehler-Danlos Syndrome.

26. •
 Mutation in the fibrillin gene.
 Fibrillin important component
of microfibrils in Elastin.
•
 Tissues affected are Skeleton,
Eyes and the CVS.
 C/F include tall stature, long
fingers, pigeon breast
deformity, hyper-extensible
joints,high arched palate, BL
subluxation of lens, floppy
Mitral valve, Aortic aneurysm
and dissection, defects in
skin,lungs.

27. • Characterized by defects in collagen synthesis.
• .Clinical Features include fragile, hyper-extensible
skin, hyper-mobile joints, grotesque contortions,
rupture of internal organs like the colon, cornea and
large arteries, poor wound healing.

29. • Familial Hypercholesterolemia:
• One of the most common mendelian disorders.
• Mutation in the LDL receptor gene.
• Hypercholesterolemia due to impaired LDL transport
into cells.
• Increased risk of atherosclerosis and coronary artery
disease.
• Increases Cholesterol leads to formation of
Xanthomas.

31. • Largest group of Medelian Disorders
• Affected individuals usually have
unaffected (carrier) parents.
• Uniform, early age of onset.
• These disorders usually involve
Enzymatic Proteins.

32.  Typical mating pattern is two
heterozygous unaffected
(carrier) individuals.
• The triat doesnot usually affect
the parent, but siblings may
show the disease
• Siblings have one chance in four
of being affecte
 Both sexes affected equally.

34. Category Disease Enzyme
Hepatic Type. Von Gierke’s
Disease type 1.
Glucose-6-
phosphotase.
Myopathic Type. McArdle
Syndrome.
Muscle
Phosphorylase.
Miscellaneous
Type.
Pompe’s Disease
type II
Lysosomal
Glucosidase.

36. • Most common X-linked disorders.
• Usually expressed only in males.
• Rarely, due to random X-inactivation, a female will express
disease, called manifesting heterozygotes.

37. • Disease usually passed on
from carrier mother.
• Expressed in male offspring,
females are carriers.
• Skipped generations are
commonly seen.
• In this case, Recurrence risk is
half of sons are affected, half of
the daughters are carriers.

38. • Recurrence risk:
• All the daughters
are heterozygous
carriers and all the
sons are
homozygous
normal.

40. • Involved in many physiologic characteristics of humans
e.g. height, weight, hair color
• Defined as one governed by additive effect of two or
more genes of small effect but conditioned by
environmental, non genetic influences

41. • The disorder becomes manifested only when a certain
number of effector genes, as well as conditioning
environmental influences are involved
• Rate of recurrence is 2 to 7%

42. COMMON DISEASES ASSOCIATED:
• Diabetes mellitus
• Hypertension
• Gout
• Cleft lip and palate
• Schizophrenia
• Bipolar disorder
• Congenital heart disease
• Skeletal abnormalities
• Neural tube defects
• Coronary artery disease

45. KARYOTYPING
• Basic tool of cytogeneticist
• Karyotype is a photographic representation in which
chromosomes are arranged in order of decreasing length
• Giemsa stain (G banding) technique—each chromosome
can be seen to possess a distinctive pattern of alternating
light and dark bands of variable widths

46. • Short arm denoted as p,
long armdenoted q .
• Each arm divided into
numbered regions from the
centromere onwards.
• Each region numerically
arranged into bands.
• For e.g., 5p24 would denote
chromosome 5, short arm,
region 2 and band 4.

47. • Cytogenetic disorders may result from
structural or numeric abnormalities of
chromosomes
• It may affect autosomes or sex
chromosomes

48. • Normal Chromosomal number is 46. (2n=46).
This is called euploidstate. (Exact multiple of
haploid number).
• Polyploidy: posession of more than two sets of
homologous chromosomes. Chromosomal
numbers like 3n or 4n. (Incompatible with life);
generally results in spontaneous abortion
• Aneuploidy: Any Chromosomal number that is
not an exact multiple of haploid number . E.g
47 or 45.

49. • Most common cause is nondisjunction of
either a pair of homologous chromosomes
during meiosis I or failure of sister
chromatids to separate during meiosis II.
• The resultant gamete will have either one
less chromosome or one extra
chromosome.

50. • Fertilization of such gamete will result in
zygote being either trisomic ( 2n+1 ) or
monosomic ( 2n-1 ).
• Monosomy in autosomes is incompatible
with life. Trisomy of certain autosomes and
monosomy of sex chromosomes is
compatible with life.

51. • The presence of two or more types of cell populations in the
same individual.
• Postzygotic mitotic nondisjunction will result in one trisomic and
one monosomic daughter cell.
• The descendants of these cells will produce a mosaic.

52. • Usually result from chromosomal breakage, resulting in loss or
rearrangement of genetic material.
• Patterns of breakage:
• Translocation.
• Isochromosomes.
• Deletion.
• Inversions.
• Ring Chromosomes.

53. • Transfer of a part of one chromosome to another
chromosome
• Translocations are indicated by t
• E.g. 46,XX,t(2;5)(q31;p14)
• Balanced reciprocal translocation is not harmful to the
carrier, however during gametogenesis, abnormal
gametes are formed, resulting in abnormal zygotes

54. • Centric fusion type or robertsonian translocation:
The breaks occur close to the centromere, affecting the
short arms of both choromosomes
Transfer of the chromosome leads to one very large and
one extremely small chromosome
The short fragments are lost, and the carrier has 45
chromosomes
Such loss is compatible with survival
However, during gametogenesis difficulties arise

56. ISOCHROMOSOMES
• Result when one arm of a chromosome is lost and
the remaining arm is duplicated, resulting in a
chromosome consisting of two short arms only or
of two long arms.
DELETION
• Loss of a portion of chromosome
• This can be terminal (close to the end of the
chromosome on the long arm or the short arm), or
it can be interstitial (within the long arm or the
short arm).
• A ring chromosome is a variant of deletion.It
occurs when break occurs at both the ends of
chromosome with fusion of the damaged ends.

57. INVERSIONS
• Occur when there are two breaks within a single
chromosome with inverted reincorporation of the
segment.
• Since there is no loss or gain of chromosomal material,
inversion carriers are normal.
• An inversion is paracentric if the inverted segment is on
the long arm or the short arm .
• The inversion is pericentric if breaks occur on both the
short arm and the long arm .

59. • Associated with absence, excess, or
abnormal rearrangements of
chromosomes.
• Loss of genetic material produces more
severe defects than does gain.
• Abormalities of sex chromosomes
generally tolerated better than those of
autosomes.

60. • Sex chromosomal abnormalities are
usually subtle and are not detected at
birth.
• Most cases are due to de novo
changes (i.e. parents are normal and
recurrence in siblings is low).

62. • Most common chromosomal disorder.
• Down syndrome is a chromosomal
abnormality characterized by the
presence of an extra copy of genetic
material on the 21st
chromosome
• Trisomy 21 is caused by a meiotic
nondisjunction event.

63. • With nondisjunction, a gamete (i. e . , a sperm or egg cell) is
produced with an extra copy of chromosome 21; the
gamete thus has 24 chromosomes
• When combined with a normal gamete from the other
parent, the embyo now has 47 chromosomes, with three
copies of chromosome 21.
• About 4% of cases are due to Robertsonian translocations.
• Maternal age has a strong influence

64.
Karyotype for trisomy Down syndrome. Notice the three copies of
chromosome 21

65. • Trisomy 18 :Edwards Syndrome.
• Trisomy 13 :Patau Syndrome.

67. • Extreme karyotypic variations seen
frequently with Sex Chromosomes, with
females having 4-5 extra X Chromosomes.
• Males with two to three Y chromosomes
have also been identified.

68. • Defined as Male Hypogonadism, develops
when there are at least two X
chromosomes and one or more Y
chromosomes.
• Usual karyotype is 47,XXY. The extra X
may be maternal or paternal.

69. • Results from nondisjunction of sex
chromosome during meiosis.
• Risk factors include advanced
maternal age and a history of
exposure to radiation in either parent.

70. • Increase in body length between soles and pubis.
• Reduced facial, body and pubic hair. Gynecomastia.
• Testicular atrophy.
• Infertility.
• Mild mental retardation.

71. • Primary hypogonadism in phenotypic
females.
• Results from partial or complete
monosomy of the X chromosome.

72. • Most common cause is absence of
one X chromosome.
• Less commonly, mosaicism, or
deletions on the short arm of the X
chromosome.

74. DIAGNOSIS OF GENETIC DISEASE
• Conventional Cytogenetic Analysis
• FISH
• Molecular Analysis