This document discusses various topics in genetics and genomics including: - Genome and genomics, which refers to the study of the entire genetic content of an individual. - Karyotyping techniques used to analyze chromosomes such as G-banding and C-banding. - Types of genetic variation like single nucleotide polymorphisms and copy number variations. - Non-coding RNAs including microRNAs and long non-coding RNAs that regulate gene expression. - Different patterns of inheritance for genetic disorders like autosomal dominant, autosomal recessive, and X-linked inheritance. - Examples of genetic disorders and their inheritance patterns including Marfan syndrome, Ehlers-Danlos syndrome, and Fabry disease

1. genetics

2. • Genome: The sum total of genetic information of an individual which
is encoded in structure of DNA
• Genomics: Is the study of genome

3. Karyotyping

4. • For karyotyping lymphocytes are used
• Lymphocytes complete cell division earlier than other cells
• Chromocytes appear early (with in 3 days of incubation in culture medium)

8. • Human genome contain 3.2 million bp
• Exon  protein encoding genes (1.5 %)
• Introns  non encoding genes
• 80 % of human genome regulate gene expression

9. G banding • Most commonly used
• Stains regions rich in AT
Q banding • Pattern is similar to G banding
C banding • Darkly stained C band centromeric region of the
chromosome corresponds to region of constitutive
heterochromatin
R banding • Reverse of geimsa stain
• Stains regions rich in GC

12. Four Common Chromosome
Staining Procedures
Banding technique Appearance of chromosomes
G-banding — Treat metaphase
spreads with trypsin, an enzyme that
digests part of chromosomal protein.
Stain with Giemsa stain. Observe
banding pattern with light
microscope.
Darkly stained G bands.
Q-banding — Treat metaphase
spreads with the chemical
quinacrine mustard. Observe
fluorescent banding pattern with a
special ultraviolet light microscope.
Bright fluorescent bands
upon exposure to
ultraviolet light; same as
darkly stained G bands.

13. Four Common Chromosome
Staining Procedures
R-banding — Heat metaphase
spreads at high temperatures to
achieve partial denaturation of DNA.
Stain with Giemsa stain. Observe
with light microscope.
Darkly stained R bands
correspond to light bands
in G-banded chromosomes.
Pattern is the reverse of G-
banding.
Banding technique Appearance of chromosomes
C-banding — Chemically treat
metaphase spreads to extract DNA
from the arms but not the
centromeric regions of
chromosomes. Stain with Giemsa
stain and observe with light
microscope.
Darkly stained C band
centromeric region of the
chromosome corresponds
to region of constitutive
heterochromatin.

17. METACENTRIC
• 2 EQUALS ARMS
WITH
CENTROMERE IN
THE CENTRE
SUBMETACENTRIC
• CENTROMERE IS
AWAY SLIGHTLY
FROM CENTRE
• X
CHROMOSOME
ACROCENTRIC
• CENTROMERE IS
TOWARDS ONE
END
• Y
CHROMOSOME
TELOCENTRIC
• NOT SEEN IN
HUMANS

18. Polymorphism

19. • two individuals share > 99.5% of their DNA sequences
• DNA sequence variation b/w 2 individuals 0.5 % (15 million bp)
• DNA sequence variation b/w 2 individual genetic polymorphism

20. Types of polymorphism
Single nucleotide polymorphism Copy number variations Repeat length polymoprhism
• MC type of polymorphism
• Single nucleotide per 1000 bp
• More than 6 million SNP
• genetic variation consisting of
different numbers of large
contiguous stretches of DNA
from 1000 base pairs to millions
of base pairs
• Short repetitive sequence of
DNA variation
• Basis of phenotypic diversity Microsatellite Minisatellite
• Present both in exons & introns
• Less than 1 % in coding regions
• 50 % of coding regions 2-6 bp repeat
size
15-70 bp reoeat
size
< 1 kilobase 1-3 kilobase

21. Non coding RNA
• Small RNA molecules  micro RNA
• Long noncoding RNA (having > 200 nucleotides in length)
microRNA Long noncoding RNA
22 nucleotides in length > 200 nucleotide length
Post transcriptional gene silencing • Promote gene activation
• Inhibit gene transcription

22. miRNA
• Donot encode proteins
• Post transcriptional gene silencing
• Inhibit gene expression by blocking mRNA
induced translation via RISC (RNA insuced
silencing complex)
• @ post transcription level

23. siRNA
• Exogenous miRNA
• Useful laboratory tool
• To study gene function  knock down technology
• Study for therapeutic agents

24. Lnc RNA
• XIST
• A type of Lnc RNA
• itself escapes X inactivation, but forms a repressive “cloak” on the X
chromosome from which it is transcribed, resulting in gene silencing.
• Emerging studies are highlighting the roles of lncRNAs in various human
diseases, from atherosclerosis to cancer

25. Epigenetic Changes
• modulation of gene or protein expression in the absence of
alterations in DNA sequence (i.e., mutation) or structure of the
encoding gene
• Useful in regulation of
• Tissue specific gene expression
• Genomic imprinting
• X chromosome inactivation
• Fragile x syndrome

26. Mutations

27. Point mutation
d/t one nucleotide is replaced by another
Frame shift mutation
d/t addition or removal of nucleotide  frameshift
Mis-sense Nonsense Silent
Yield
different type
of proteins
Mutation lead to
termination
In sickle cell
anemia
Thalassemia

28. Pleiotropism
• Single mutant gene produces multiple end effects
• Sickle cell anemia  multiple effects like sickling RBC / splenic infarction

29. Genetic heterogeneity
• Multiple gene  single end effect
• DM

30. Gene disorders

31. Single gene disorders Multifactorial inheritance Chromosomal disorders
Classic mendelian
inheritance
Non menedelian
inheritance
• Complex polygenic inheritance
 2 or more mutant genes +
environmental factors
 DM
 Cleft lip & palate
 Coronary heart disease
 HTn
 Gout
Structural Numerical
• Euploidy
• Aneuploidy
• Deletion
• Translocation
• Ring
chromosome
• Isochromosome
• Inversion
• AR
• AD
• XR
• XD
• Trinucleotide
repeat
mutation
• Mitochondrial
inheritance
• Genomic
imprinting
• Gonadal
mosaicism

33. PEDIGREE ANALYSIS

37. AUTOSOMAL DOMINANT

38. AUTOSOMAL RECESSIVE

39. X LINKED RECESSIVE

40. MITOCHONDRIAL INHERITANCE

41. X LINKED RECESSIVE

42. SINGLE GENE DISORDERS

43. • SINGLE GENE OR MENDELIAN INHERITANCE
• CODOMINANT INHERITANCE
• PENETRANCE
• VARIABLE EXPRESSIVITY
• PLEIOTROPISM
• SINGLE MUTANT GENE PRODUCING MULTIPLE END EFFECTS

44. AUTOSOMAL DOMINANT
AUTOSOMAL DOMINANT MOST COMMON
PATTERN OF INHERITANCE

45. AUTOSOMAL DOMINANT
• ALL GENERATIONS ARE
AFFECTED
• DONOT SHOW GENDER BASIS

46. AUTOSOMAL DOMINANT
• VARIABLE EXPRESSIVITY
• IMCOMPLETE PENETRANCE
• Denovo germ cell mutation
• LOSS OF FUNCTION TYPE MUTATION IS MORE COMMON

47. DIFFERENT EFFECT
CAUSED BY SAME
MUTANT GENE
WITH MUTATED GENE BUT
PHENOTYPICALLY NORMAL

49. MARFAN SYNDROME
• AD
• MUTATION IN FBN1 GENE CODING
FOR FIBRILLIN

51. SUPEROTEMPORAL DISLOCATION
OF LENS

54. CARDIOVASCULAR MANIFESTATION
• MOST COMMON VALVULAR LESION
IS MVP
• AORTIC CYSTIC MEDIAL
DEGENERATION
• MOST COMMON CAUSE OF DEATH
IS AORTIC DISSECTION

56. HYPER EXTENSIBILITY

58. ARACHNODACTYLY

60. REVISED GHENT CRITERIA
• FAMILY HISTORY
• CARDINAL CLINICAL SIGNS
• FIBRILLIN MUTATION

61. EHLERS DANLOS SYNDROME
• ALL PATTERN OF MENDELIAN
INHERITANCE ARE SEEN BUT
MOST COMMON IS AD
• DEFECTIVE COLLGEN
SYNTHESIS
• MC AFFECTED COLLAGEN
TYPE 3

62. EHLERS DANLOS SYNDROME
HYPEREXTENSIBLE SKIN
RUBBER MAN
SYNDROME

63. ABNORMAL WOUND HEALING IN EHLER
DANLOS  CIGARETTE PAPER LIKE SCAR

64. • EHLERS DANLOS SYNDROME HAS ALL 3 PATTERNS OF INHERITANCE

65. MC IS TYPE III

66. TYPE I CLASSICAL • MVP
• DIAPHRAGMATIC HERNIA
TYPE III HYPERMOBILITY TYPE MOST COMMON TYPE
TYPE IV VASCULAR TYPE • RUPTURE OF COLON
• RUPTURE OF VESSELS
• MOST SERIOUS TYPE
• WORST PROGNOSIS
• SUDDEN DEATH
TYPE VI OCULO SCOLIOTIC
TYPE VII ATHRROCHALASIA • BLUE SCLERA
• RETINAL DETACHMENT
• CORNEAL RUPTURE
• KYPHOSCOLIOSIS
LEAST COMMON
TYPE VIII PERIODONTIC • PREMATURE LOSS OF TEETH

67. Autosomal recessive

68. Autosomal recessive
• Most of the inborn errors of metabolism
• Characteristic of AR
• More uniform expression of the disease
• Complete pentrance
• Early onset of disease
• Enzymes are commonly affected

69. Autosomal recessive inheritance
• Most inborn errors of metabolism
• Glycogen storage disease
• Lysosomal storage disease

71. Autosomal dominant Autosomal recessive
de novo germ cell mutation common Rare
Penetrance incomplete complete
Expressivity Variable Uniform
Onset of disease Late onset Early
Affected protein Structural protein Enzymes are affected

72. • All lysososmal storage disease are AR
• Except for hunters & fabrys disease (which are x linked recessive )

74. GAUCHER DISEASE
• AR
• MOST COMMON LYSOSOMAL
STORAGE DISORDER

75. CRUMPLED TISSUE PAPER APPEARANCE
ELONGATED
LYSOSOMES CONTAING
LIPIDS IN BILAYER
STACCKS

78. Fabrys disease
• Angiokeratomas & neuropathic pain
• d/t deficiency of alfa galctosidase
Angiokeratoma

81. Deficiency of alfa galactosidase  fabrys
disease

82. Maltese cross d/t lipid inclusions

85. X LINKED DOMINANT
• RARE PATTERN
• AFFECTED MALE WILL TRANSMIT THE DISEASE TO 100 % OF THEIR
DAUGHTERS
• AFFECTED FEMALE WILL TRANSMIT THE DISEASE TO 50 % OF THEIR
SONS & DAUGHTERS

86. X LINKED DOMINANT

88. Genomic imprinting
• o Human inherits two copies of each gene, i.e. two alleles, from homologous maternal and
paternal chromosomes.
• o There is no functional difference between the genes derived from mother or the father.
• o But, with respect to some genes, there are functional differences between the paternal gene
and maternal gene.
• o These differences result from an epigenetic process, called genomic imprinting.
• o In most cases, genomic imprinting selectively inactivates either the maternal or paternal allel.
• 1. Maternal genomic imprinting
• • Selective inactivation of maternal allel
• • Example is Angelman syndrome
• 2. Paternal genomic imprinting
• • Selective inactivation ofpatemal allel.
• • Example is Prader-willi syndrome.

89. Genomic imprinting
• Epigenetic process resulting in
differential inactivation of either
maternal or paternal alleles of certain
genes
• Heritable chemical modification
• Methylation of DNA or acetylation of
histones
• Decreases genetic expression (with out
affecting primary DNA sequence
EPIGENETICS)
• Occurs in sperm or ova before
fertilisation

94. Trinucleotide repeats

95. Not diseased but increased
susceptibility to get diseased
in next generation
premuttion (d/t genetic
anticipation)

96. Genetic anticipation
• In trinucleotide repeats
• Increase in severity in successive
generation
• Symptoms appear in an earlier age
• Premutation

97. Fragile x chromosome

101. Macrorochidism in post pubertal period
• Long face
• Large mandible
• Large everted ears
• High arched palate
• MVP
• Hyperextensible joints

102. • Inversion refers to a
rearrangement that involves two
breaks within a single chromosome
with reincorporation of the
inverted, intervening segment.
• It can be of the following two
types:
• a. An inversion involving only one
arm of the chromosome is known as
paracentric.
• b. If the breaks are on opposite sides
of the centromere, it is known as
pericentric

104. Mitochondrial inheritance

105. PATERNAL MITOCHONDRIA
LEFT OUTSIDE THE OVUM
ONLY MATERNAL
MITOCHONDRIA IS
TRANSFERRED TO ZYGOTE

106. MITOCHONDRIAL INHERITANCE
INFECTED MOTHER TRANSMITS
INFECTION TO ALL HER CHILDREN
NO TRANSMISSION FROM
INFECTED MALE

108. Heteroplasmy in mitochondrial inheritance

109. Mitochondrially transmitted disease
• LHON
• MELAS
• Mitochondrial encephalopathy lactic acidosis & stroke like syndrome

110. Chromosomal anomalies

111. Cat eye syndrome
 trisomy
chromosome 22

112. Cat eye syndrome
• Partial tetrasomy or trisomy of chromosome 22
• Coloboma iris

113. Klinefelter syndrome

119. Testes on biopsy
• Grossly atrophic
• on biopsy hyalanisation of seminiferous tubule
• Adenomatous clumping of sertoli cells
• Azoospermia

120. • Rx
• Testosterone at 11 – 12 years of age

121. Advanced paternal age
• Neurofibromatosis
• Marfan syndrome
• Klinefelter syndrome
Advanced maternal age
• Down syndrome
• XXX syndrome
• Klinefelter syndrome

122. Turner syndrome

123. • Mosaic with with XY pattern is associated with
gonadoblastoma & virilisation

124. • Single X chromosome is maternal in origin in 75 % of patients

125. Webbed neck  lymphatic dilation

132. • No of genomes in human gene  1,00,000