This document provides information on autosomal recessive disorders. It discusses their pattern of inheritance, categories including metabolic, hematopoietic, endocrine, skeletal and nervous disorders. Specific disorders discussed in more detail include cystic fibrosis, phenylketonuria, galactosemia, lysosomal storage diseases like Tay-Sachs disease, Niemann-Pick diseases, Gaucher disease, and mucopolysaccharidoses. The pathogenesis, clinical manifestations, morphology, and diagnosis of each condition are summarized.

2. Autosomal Recessive Disorder
Presented By:
Aamir Sharif
M.Phil Human Pathology

3. Autosomal Recessive Disorder
• Largest category of Mendelian disorder
• Usually does not affect the parent of the affected individual,
but sibling may show the disease.
• Complete penetrance is common.
• Onset is frequently early in life.
• NEW mutations rarely detected clinically
• Usually affect enzymatic proteins (show LOSS of
FUNCTION)

4. Pattern Of Inheritance:
 Typical pattern is two
heterozygous unaffected
(carrier) parent.
• The triat does not usually
affect the parent, but siblings
may show the disease
• Siblings have one chance in
four of being affected
 Both sexes affected equally.

5. Autosomal Recessive Disorder
Metabolic
Cystic fibrosis , Phenylketonuria
Galactosemia , Homocystinuria
Glycogen storage disease
Hematopoietic
Sickle cell anaemia
Thalassemias
Endocrine Congenital Adrenal hyperplasia
Skeletal Alkaptonuria
Nervous
Friedrich ataxia
Spinal muscular atrophy

6. Cystic Fibrosis (Mucoviscidosis)
• Autosomal recessive
• Most common lethal genetic disease affecting
Caucasians (1 in 3,200 live births in the USA)
– 2-4% of population are carriers
– Uncommon in Asians and African-Americans
• Widespread disorder in epithelial chloride transport
affecting fluid secretion in
–exocrine glands
– epithelial lining of the respiratory, gastrointestinal,
and reproductive tracts
• Abnormally viscid mucus secretions

7. Pathogenesis
• Primary defects in CF is abnormal function of an
epithelial choloride channel protein encoded by the
Cystic Fibrosis Transmembrane Conductance
Regulator (CFTR) gene at chromosome no 7.

8. CFTR Gene: Normal
• Cystic Fibrosis Transmembrane Conductance Regulator
(CFTR)
• CTFR → epithelial chloride channel protein
– agonist induced regulation of the chloride channel
– interacts with epithelial sodium channels (ENaC)
• Sweat gland
– CTFR activation increases luminal Cl− resorption
– ENaC increases Na+ resorption
– sweat is hypotonic
• Respiratory and Intestinal epithelium
– CTFR activation increases active luminal secretion of chloride
– ENaC is inhibited

9. CFTR Gene: Cystic Fibrosis
• Sweat gland
– CTFR absence decreases luminal Cl− resorption
– ENaC decreases Na+ resorption
– sweat is hypertonic
• Respiratory and Intestinal epithelium
– CTFR absence decreases active luminal secretion of chloride
– lack of inhibition of ENaC is opens sodium channel with
active resorption of luminal sodium
– secretions are decreased but isotonic

10. Chloride Channel Defect and Effects
• Chloride channel defect in the sweat duct (top) causes increased
chloride and sodium concentration in sweat.
• In the airway (bottom), cystic fibrosis patients have decreased chloride
secretion and increased sodium and water reabsorption leading to
dehydration of the mucus layer coating epithelial cells, defective
mucociliary action, and mucus plugging of airways predispose to
recurrent pulmonry function.

11. CFTR Gene: Mutational Spectra
• More than 800 mutations are known
• These are grouped into six classes
– mild to severe
– In severe case there is complete loss of
CFTR
– Occurs in 70% of CF chromosomes
– 3 base pair deletion leading to absence of
phenylalanine at position 508 (DF508) of the
CF transmembrane conductance regulator
(CFTR)

12. Genetics of CF
• DF508 mutation leads to improper processing and
intracellular degradation of the CFTR protein
• Other mutations in the CF gene produce fully
processed CFTR proteins that are either non-
functional or partially functional

13. Morphology
• Plugging of ducts with viscous mucus and loss of ciliary
function of respiratory mucosa
• Pancreas
– atrophy of exocrine pancreas with fibrosis
– islets are not affected
• Liver
– plugging of bile canaliculi with portal inflamation
– biliary cirrhosis may develop
• Genitalia
– Absence of vas deferens and azoospermia
• Sweat glands
– normal histology

14. Pancreas in Cystic Fibrosis.
Note that the ducts contain
inspisated material and the acini are
atrophic and the stroma exhibits
fibrosis and chronic inflamation. The
islets are preserved. Normal pancreas for comparison

15. Lung Pathology in CF
• More than 95% of CF patients die of
complications resulting from lung infection
• Viscous bronchial mucus with obstruction and
secondary infection
– S. aureus
– Pseudomonas
– Hemophilus
• Bronchiectasis
– dilatation of bronchial lumina
– scarring of bronchial wall

16. • Lungs of a patient dying
of cystic fibrosis.
• There is extensive mucus
plugging and dilation of
the tracheobronchial
tree. The pulmonary
parenchyma is
consolidated by a
combination of both
secretions and
pneumonia—the green
color associated with
Pseudomonas infections.

17. Manifestations
• Common presentations
– Chronic cough
– Recurrent pulmonary infiltrates
– Failure to thrive
– Meconium ileus

18. Manifestations
• Respiratory tract
– Chronic sinusitis
• Nasal obstruction
• Rhinorrhea
• Nasal polyps in 25%; often requires surgery
– Chronic cough
• Persistent
• Viscous, purulent, green sputum

19. CF Diagnosis
• Clinical criteria
• One are more characteristic phenotypic features OR
history of cystic fibrosis in siblings or positive new
born screening test result
• Or inc Sweat chloride concentration on two or more
occasion
• DNA Analysis
– gene sequencing

20. PHENYLKETONURIA
(PKU)
• Ethnic distribution
– common in persons of Scandinavian descent
– uncommon in persons of African-American and Jewish descent
• Autosomal recessive
• 98 % cases of PKU is due to Phenylalanine hydroxylase
deficiency and 2 % arise from abnormalities in synthesis or
recycling of the cofactor tetrahydrobiopterin.
• Affected patients are normal at birth but within a week exhibt
a rising plasma phenylalanine level.
• At 6 months less than 4 % untreated patients show mental
retardation.
• About one 3rd are never able to walk and two 3rd talk.
• Decreased pigmentation of hair and skin often accompany
metal retardation.

21. Pathogenesis & C/F
• Normally 50% of dietary intake of phenylalanine is
necessary for protein synthesis and rest is converted into
tyrosine by PAH.
• When phenylalanine metabolism is blocked because of a
lack of PAH enzyme, minor shunt pathways come into
play, yielding several intermediates that are excreted in
urine and sweat that impart a strong musty or mousy
odor to affected infants.
• Excess phenylalanine and its metabolites contribute to
the brain damage in PKU.
• Concomitant lack of tyrosine, a precursor of melanin is
responsible for the light color of skin and hair.

22. Diagnosis
• Approximately 500 mutant alleles of PAH gene have
been identified, only some of which cause a severe
deficiency of the enzyme.
• Those with 6% residual activity present with milder
disease.
• Some mutation results in modest elevations of blood
phenylalanine without associated neurological
damage (benign hyper phenylalaninemia).
• Serum phenylalanine levels differentiate BHP from
PKU.

23. GALACTOSEMIA
• Autosomal recessive disorder affects 1 in 60,000 live-born
infants.
• Normally Lactose → glucose + galactose
• Galactose-1-phosphate uridyl transferase (GALT)
– GALT is involved in the first step in the transformation of
galactose to glucose
– Lack of this enzyme due to homozygous mutation in the
encoding gene GALT → galactosemia
– As a result of this transferase deficiency, glactose-1-
phosphate,and galactitol accumulate in manny tissues,including
liver, spleen, lens of eyes, kidney and cereberal cortex.

24. Pathogenesis
• Fatty changes Hepatomegally
• Glactititol swells in lens Opacity of lens Cataract
• CNS Loss of nerve cell, Gliosis, edema.
• Infants affected by galactosemia typically present with
symptoms of lethargy, vomiting, diarrhea, failure to
thrive, and within a few days of milk ingestion.
• Jaundice and hepatomegally in first week
• Accumulation of metabolites in kidney impair A.acid
transport resulting in aminoacidurea.
• E.coli septicemia occur frequently.

25. • Presences of reducing sugar other than glucose in
urine
• Transferase dificiency in leukocyte and RBC
• Antenal GALT activity assay in cultured amniotic fluid
cells
• Or Galactilol level in amniotic fluid supernatant.

26. Lysomal storage disease
• Lysosome breakdown complex substrates like sphingoloipids ,
mucopolysaccharides into soluble end products.
• Inherited deficiency of lysosomal enzyme, catabolism of its
substrate remain incomplete, leading to accumulation of
partially degraded metabolites into lysosomes.
• Approximately 40 lysomal storage diseases are identified that
shows certain common features.
Autosomal recessive transmission
Pt. population consisting of infants and young children.
Storage of insoluble intermediates in the mononuclear
phagocyte system, giving rise to hepatospleenomegaly.
Cellular dysfunction not only by undigested material but
also by activation of macrophages and release of
cytokines.

27. Tay-Sachs Disease
• It is characterized by accumulation of gangliosides principally
in the brain as a result of a mutation in and consequent
deficiency of the β subunit of the hexosaminidase A.
• Based on gangliosides these disorders are sub classified into
GM₁ and GM₂
• GM₂ is the most common gangliosides.
• More than 100 mutations have been described; most affect
protein folding or intracellular transport.
• The brain is principally affected because it is involved in
gangliosides metabolism.
• GM₂ storage occur throughout the CNS.

28. • The molecular basis of neuronal injury is not fully
understood.
• Because in many cases the mutant protein is
misfolded, so called “unfolded protien” response.
• If such misfolded protein are not stabilized by
chaperones they triggers appoptosis.

29. Morphology
• Affected cell appear swollen and sometimes foamy.
• Electron microscopy reveals whorled configuration
within lysosomes composed of onion-skin layers of
membranes throughout the CNS.
• In Retina there is pallor produced by swollen
ganglion cells in the peripheral retina result in
contrasting “cherry red” spot in the relatively
unaffected central macula.

30. • In the most common acute infantile variant of Tay-Sach
disease infants appear normal at birth but motor
weakness begin at 3 to 6 month of age followed by
neurological impairment, onset of blindness and
progressively more severe neurological dysfunction.
• Death occur within 2 or 3 years.
• Level of Hexosaminidase in the serum or DNA analysis of
Heterozygote carriers has a diagnostic importance

31. Niemann-Pick Disease Type A and B
• Niemann-Pick Disease Type A and B diseases are
characterized by a primary deficiency of a sphingo-
myelinase and the resultant accumulation of
sphingomyelin.
• In type A severe deficiency of sphingo-myelinase, the
break down of sphingomyelin into ceramide and
phosporylcholine is impaired and excess sphingomyelin
accumulates in all phagocytic cell and in the neuron.
• Macrophages become stuffed with droplets of the
complex lipid, imparting a fine vacculation or foaminess
to the cytoplasm.

32. Morphology
• Electron microscopy confirms that vacuoles are engorged
secondary lysosomes that often contain cytoplasmic bodies
resembling concentric lamellated myelin figures, sometimes
called “zebra ” bodies.
• Because of their high content of phagocytic cells, the organ
most severely affected are spleen, liver, bone marrow, Lymph
nodes and lungs.
• That lead to visceromegaly and severe neurologic
deterioration but in type 2 only visceromegaly.
• Death occur within first 3 year of life.
• Estimation of Sphingomyelinase activity in the leukocytes or
cultured fibroblast can be used for diagnosis of suspected
case and carriers.
• Antenatal diagnosis is possible by enzyme assay or DNA probe
analysis.

33. Niemann-Pick Disease Type C
• It is more common than Type A and B.
• Mutation in 2 related gene NPC1 and NPC2
• NPC1 is being responsible for a majority of cases.
• Niemann-Pick Disease Type C is due to primary
defect in lipid transport that lead to accumulation of
cholesterol and gangliosides GM₁ and GM₂ in the
affected cells.
• NPC is clinically hetrogeneouses
• The most common manifestation are: ataxia,
dystonia, vertical supra nuclear gaze, dysarthria, and
psychomotor regression.

34. Gaucher Disease
• Normally Glycolipids derived from the breakdown of
senescent blood cell are degraded in liver , spleen, and bone
marrow into ceramide and then into glucose by
glucocerebrosidases .
• Deficient glucocerebrosidases lead to accumulation of
glucocerebrosides in mononuclear phagocytic cells that result
in enlargment of Phagocytes “Gaucher cells” upto
1micrometer.
• Accumulation of distended lysosmes gave cytoplasm a
characterized appearance “wrinkled tissu paper”
• No distnict vacuolation is present.
• This disease is caused not just by the burden of storage
material but also by activation of the macrophages and
derived cytokines.

35. • 3 Autosomal recessive variants of Gaucher disease
• Type 1 also called chronic non neuronopathic form account
for 99% of cases and characterized by
• Clinical or radiographic bone involvement 70-100%
(osteopenia, focal lytic lesion and osteonecrosis)
• Hepatospleenomegaly and abscence of CNS involvement
while in Type II and Type III neurologic manifestation
(convulsion, progressive deterioration) appear during infancy
and in adulthood
• Gaucher cells are found in the liver , spleen, lymph nodes and
bone marrow
• Estimation of glucocerebrosides level in the leukocytes or
cultured fibroblast can be used for diagnosis of suspected
case and carriers.

36. Mucopolysaccharidoses
• Mucopolysaccharides form a part of ground substance and
are synthesized by connective tissue fibroblasts.
• Certain fraction is degraded within lysosomes.
• The lack of lysosomal enzymes leads to accumulation of
mucopolysaccharides in lysosomes.
• Several clinical variants of MPS classified numerically from
MPS I to MPS VII.
• Mucopolysaccharides that accumulate in tissues are
Dermatan sulphate, heparaan sulphate, keratan sulphate
and Chondroitin sulphate.
• Hepatospleenomegaly, skeltal deformities, lesion of heart
valves and sub endothelial arterial deposits and lesion in
brain are common in all MPS.

37. Type I Huler syndrome
• It is caused by a deficiency of alpha-L-iduronidase
• Children have a life expectancy of 6-10 yr and death is
often due to cardiac complications.
• Accumulation of dermatan sulphate and heparan
sulphate is seen in cells of mononuclear phagocyte
system, in fibroblast, within endothelium and smooth
muscle cells of vascular wall.
• The affected cell are swollen and have clear cytoplasm,
resulting from accumulation of material positive for
periodic acid-Schiff staining within engorged, vaculated
lysosomes.
• Lysosomal inclusions are also found in neurons
accounting for mental retardation

38. MPS type II or Hunter Syndrome
• Differ from Hurler syndroms in its mode of of
inheritance (X-linked), the absence of corneal
clouding and often milder in clinical course.
• Accumulation of dermatan sulphate and heparan
sulphate from deficiency of L-iduronate sulpatase.

39. Glycogen Storage Diseases (Glycogenosis)
Clinicopathol
ogical
Catageory
Specific type Enzyme
deficiency
Morphologic changes Clinical Features
Hepatic Type Hepatorenal
( von Gierke
disease)
Glucose-6-
phosphatase
Hepato spleenomegally :intra
cytoplasmic accumulation of
glycogen small amount of lipids
Renomegally:
intra cytoplasmic accumulation
of glycogen in cortical tubules
In untreated pt.
Hepatomegaly
Hypoglycemia
Hyperlipidemia
Hyperuricemia
Bleeding tedency
With treatment:
Patients surive and develop
hepatic adenomas
Myopathic
Type
McArdle
Syndrome
(type v)
Muscle
phosphorylase
Glycogen in subsarcolemmal
location in skelton muscle
Painfull cramps after sternous
exercises
No rise in lactate level in
venous blood
Myoglobinurea in 50% cases
Miscellaneous
Type
Generalized
glycogenosis
(pompe
disease type II)
Lysosomal
glucosidase (acid
maltase)
Cardiac and hepatomegaly
Lacy cytoplasmic pattern(due to
glycogen deposition)
Massive cardiomegally
Muscle hypotonia
Cardiorespiratory failure
before 2 yr

40. ss
40

41. Definition and Molecular Basis of Disease
• Sickle cell disease (SCD): a recessively inherited
chronic hemolytic anemia
• Caused by a single nucleotide substitution in the β
globin gene on chromosome 11
– Hemoglobin S (most common): GTG  GAG results in
substitution of valine (hydrophobic) for glutamate
(hydrophilic)
– Many other variant hemoglobins are described
• Mutant hemoglobin polymerizes under low oxygen
conditions and form bundles that distort red cells
into the classic sickle shape

42. Prognosis
• Over the past 30 years in US/Europe, median survival
has increased from 14yrs to 45-55yrs for SS disease
• Figures not available for Africa but estimated 50% of
affected die before 5yrs
• WHO estimates that SCD complicates up to 9% of
under 5 deaths in West Africa

43. Normally, humans have
Of these, Haemoglobin A makes up around 96-97% of
the normal haemoglobin in humans.
Haemoglobin
A two alpha two beta
A2 two alpha two delta
F two alpha two gamma
43

44. Common types of Sickle Cell
Disorders
Type of anaemia Hemoglobin variation comment
Sickle Cell Anemia Sickle haemoglobin (HbS)
+ Sickle haemoglobin
Most Severe – No
HbA
Hemoglobin S-Beta
thalassemia
Sickle haemoglobin (HbS)
+ reduced HbA
Mild form of Sickle
Cell Disorder
Hemoglobin S-C disease Sickle haemoglobin (HbS)
+ (HbC)
Mild form of Sickle
Cell Disorder
Sickle Cell Trait Sickle haemoglobin (S) + 44

45. 45

46. Pathophysiology
Is caused by
• point mutation in the β-globin chain of Hb
glutamic (hydrophobic amino acid)
valine( hydrophilic )
• at the 6th position
Life span
• RBC 90–120 days
• sickle cells 10–20 days.

47. • exposure to P O2 < 40 mmHg for 2 to 4 minutes
• polymerization of Hb
• The initiation of polymerization may be -
incomplete and
-reversible , if re-oxygenation occurs early in the
process.
• Repetitive exposure to alternating de-oxygenated and
oxygenated states lead to
-membrane distortion,
-irreversible sickling.

48. 48
Pathophysiology
Deoxygenation
polymerization of hemoglobin
sickling of red cells
endothelial damage/activation
RBC and leukocyte adhesion to
endothelium, vasoconstriction
vascular occlusion, organ ischemia
and end-organ damage

49. OXY-STATE DEOXY-STATE

51. Initial Clinical Presentation
• Typically presents in infancy after 6 months of age,
when Hb F is waning
– Birth hemoglobin F: α2γ2
– Hemoglobin A: α2β2
– Hemoglobin S: α2S2
• Pain and anemia are hallmarks of disease

52. Initial Clinical Presentation
• Suggestive historical findings:
– Family history of known SCD
– Family history of sudden death in young child
– Frequent pain
– Frequent chest infections
– Failure to gain weight despite good nutrition
– Persistent jaundice
– Classic sequelae (hand/foot syndrome, priapism)

53. Initial Clinical Presentation
• Physical Exam findings are nonspecific:
– scleral icterus
– pale mucous membranes
– systolic murmur throughout precordium
– splenomegaly

54. Initial Clinical Presentation
• Predictors of adverse outcome at presentation:
– Dactylitis (iinflammation of an entire digits) in
infant <1y/o
– Hb<7g/dL
– leukocytosis absent infection
– priapism

55. Sequelae: Vaso-occlusive/pain crisis
• Occurs in 60% of SS patients when vaso-
occlusion tissue ischemia
• May be triggered by infection, temperature
extremes, dehydration or stress but usually w/o
identifiable cause.
• Characterized by severe pain often in
extremities, involving the long bones, or the
abdomen. May last hours to days.
• Number of pain crises/year varies widely
between individuals with some patients w/
constant low level pain.

56. Sequelae: Infection
• By age 1 30% of Hb SS pts are asplenic, by age
6, 90% are asplenic due to microinfarcts.
• This makes children especially vulnerable to
infection/sepsis with encapsulated organisms,
esp. Strep pneumoniae (400x higher risk vs.
general population)
• Sickle Cell patients are also more susceptible
to osteomyelitis (Salmonella and Staph spp.)

57. Sequelae: Acute Chest Syndrome
• Characterized by new respiratory distress, CXR
infiltrate, hypoxia(O2<95%) and/or chest pain
• Occurs in 40% of patients with SS disease
• Can progress rapidly to ARDS
• May be caused by viral or bacterial infection,
fat embolism(2/2 bone marrow infarction),
cause unknown in most cases

58. Sequelae: Stroke
• 11% of SS patients have a stroke by age 20
with peak incidence between 2 and 10
• Presents as focal neurologic deficit or seizure

59. Sequelae:
Acute Splenic Sequestration
• Sudden enlargement of the spleen
accompanied by a >2g/dL decrease in Hb from
baseline, often w/ thrombocytopenia
• Occurs in children <3y/o
• Can cause sudden circulatory collapse

60. Sequelae: Aplastic Crisis
• Caused by infection with Parvovirus B19 (fifth
disease) which invades young erythroblasts in bone
marrow
• Often presents with fever, URI sx and drop in Hb
• RBC life expectancy in SS disease is 10-20 days, thus
decrease in RBC production has profound effect.
• Bone marrow recovery typically within 7-10 days

61. Sequelae: Anemia
• Compensated anemia at baseline
• Baseline Hb normally 8-9 g/dl
• Overtransfusion can predispose to transfusion
transmitted infections and iron overload

62. Other Sequelae
• Priapism
• Dactylitis (hand-foot syndrome): painful swelling of
hands and feet which occurs in infants.
• Avascular necrosis of the humeral/femoral head
• Cholelithiasis
• Retinopathy
• Chronic leg ulcers

63. Laboratory investigations
Complete blood count
 Level of Hb -: 6–8 g/dL
(Normal range-: Male=13.5-17.5g/dl Female=11.5-15.5g/dl)
 High reticulocyte count (10–20%).

64.  Blood film
The blood film is microcytic and hypocromic
Sickled cell anaemia Normal
64

65. 65

66. Sickle solubility test
 Mixture of Hb S in a
reducing solution
 Gives a turbid
appearance
(Precipitation of Hb S)
 Normal Hb gives a
clear solution
66

67. Hb electrophoresis
• To confirm the diagnosis.
• There is,
no Hb A
80–95% Hb SS
2–20% Hb F
67

68. Results of laboratory examination in sickle cell anaemia
Laboratory
examinations
results Values in this
disease
Values in health
WBC count increased 10000 -30000 5000 -10000
RBC count decreased 1 -4 million/mm3 4 -6 million/mm3
Hb count decreased 6 -8g/100ml Male=13.5-17.5g/dl
Female=11.5-
15.5g/dl
Haematocrit reading decreased 10 -30% 45%
Reticulocyte count increased 10-40% 1-2%
Hb electrophoresis positive HbS & HbF HbA
Urine analysis Albumin casts positive negative
Serum bilirubin increased 1-3 mg/100ml 0.2-0.8mg/100ml
Platelet count increased 40000-50000/mm3 150000-
400000/mm3
Bone marrow
exanination
Increased red cells 40-70% 8-30%
68

69.  Tests to detect sickle cell genes before birth
 Diagnosed in an unborn baby
 Sampling amniotic fluid
 Look for the sickle cell gene
69

71. Fluorescent in situ hybridization
• Fluorescent in situ hybridization, also known as
fluorescence in situ hybridization, is more commonly
referred to as FISH.
• It is a technique used to detect the presence or
absence and location of specific gene sequences
• Can visualize specific cytogenetic abnormalities (copy
number aberrations)
– chromosomal deletion, amplification,
translocation

72. • FISH is fast and accurate at finding it.
• It can also be performed even if cells are not actively
dividing, and it provides more specific information
about abnormalities in chromosomes.
• More conventional techniques, such as karyotyping,
simply tell investigators the number and size of
chromosomes within a cell.
• Such analysis can be performed on prenatal samples
(amniocentesis, chronic villus biopsy, umbilical cord
blood ) , peripheral blood lymphocytes.

73. How does FISH work?
• FISH identify where a particular gene falls within an individual's
chromosomes.
• The first step is to prepare short sequences of single-stranded
DNA that match a portion of the gene the researcher is looking
for. These are called probes.
• The next step is to label these probes by attaching one of a
number of colors of fluorescent dye.
• DNA is composed of two strands of complementary molecules
that bind to each other like chemical magnets.
• Since the researchers' probes are single-stranded, they are able
to bind to the complementary strand of DNA, wherever it may
reside on a person's chromosomes.
• When a probe binds to a chromosome, its fluorescent tag
provides a way for researchers to see its location.

74. Interpretation of FISH
• Each fluorescently labeled probe that hybridizes to a
cell nucleus in the tissue of interest will appear as a
distinct fluorescent dot
– Diploid nuclei will have two dots
– If there is duplication in the region of interest, the gain
will result in more than two dots
– If there is a loss in the region of interest, one or zero dot
will result