Inherited disorders can be caused by genetic abnormalities passed down from parents or spontaneous genetic mutations. Diagnosis techniques include DNA probes tagged with radioactive isotopes to detect mutations, restriction enzyme analysis to study DNA fragments, and analysis of disease-related genes using PCR and fluorescent in situ hybridization. Examples provided are diagnosis of sickle cell anemia, cystic fibrosis, tuberculosis, cancer, and Down syndrome.

1. DIAGNOSIS OF INHERITED
DISORDERS
Vishnupriya.C
II M.Sc
BIOCHEMISTRY

2. INHERITED DISORDERS:
is a genetic problem caused by one or more
abnormalities in the genome
 There are certain conditions in which genetic changes
are the main cause for this condition.
These are known as inherited disorders or genetic
disorder
it can also be caused due to mistakes in protein instructions

3. CAUSES:
• Inheritance from parents to off spring
• Alterations in the personal habits
• Environmental influence
• Genetic alterations in the gene
• Damage in the chromosome ie: change in number or structural
change of entire chromosome
• Mutations in the multiple genes

4. DNA PROBES
• It is a genetic probe and single stranded DNA molecule
• that can recognize and bind to target DNA
MECHANISM
• Based on the principle of denaturation and renaturation
• The double stranded DNA is subjected to physical and chemical
Eg: temperature >95c
PH < 10.5
•In favourable conditions they reunite and form double stranded DNA

5. RADIO ACTIVE DETECTION SYSTEM
• DNA probe is synthetically tagged with radioactive isotope usually
phosphorous 32 ie:P32
• The target DNA is purified and denatured and it is mixed with DNA
probes which is radioactively labelled
• The isotope labelled DNA specifically binds and hybridizes with the
target DNA
• The non – hybridized DNA is washed away
• The presence of radioactivity in the hybridized DNA can be
detected with the help of autoradiography

6. SICKLE CELL ANEMIA
• disease occurs mainly due to the single cell mutation in the beta
chain of globin
• In normal condition the DNA sequences is CCT GAG GAG
• But in disease condition the DNA sequences is altered CCT GTG GAG
•so the protein coded by the gene is altered as Glutamate
DIAGNOSIS:
•The single cell mutation can be detected using Restriction enzyme
Mst 11
• It is used to cut the DNA fragments in and around of beta globulin
gene
• it is followed by the electrophoresis of DNA fragments

7. •When a probe is attached to the segment of DNA hybridization will
occur only in case of damaged cell
CYSTIC FIBROSIS:
•characterized by the accumulation of dehydrated mucous in the
respiratory tract and lungs
•In normal condition the chloride ions are pushed out of the cells with
the help of protein CYSTIC FIBROSIS TRANSMEMBRANE PROTEIN
• affected person carriers of one mutation of the CFTR gene and Gene
Deletion Delta F 508
• CF patients has insufficient pancreatic function.
•Delta F 508 causes the loss of phenylalanine in a supposed CF
transmembrane regulation protein which affects a prospective ATP-
binding site and affects regular transport of chloride ions

8. DIAGNOSIS :
• Strong linkage disequilibrium has been shown between two
polymorphic loci
• defined by the DNA probes KM19 and XV-2c
TUBERCULOSIS :
• Caused by mycobacterium tuberculli
• generally affects the lungs but can also affect
other parts of the body.
• certain cases it doesn’t show no symptoms it
is latent tuberculosis

9. DIAGNOSIS:
• the luciferase reporter gene were constructed from phAE39 gene and
firefly luciferase gene was inserted into potent promoter of heat
shock protein 60
• Genetically engineered phage is added to culture medium of M.
tuberculosis
• Phage attaches to the bacterial cell penetrates and mycobacterium
tuberculosis chromosome which inserts leucin gene in
mycobacterium
• Enzyme luciferase is produced by the bacteria
• Luciferase ATP is added to the culture medium
• Light is detected by Leuminometer
•In the presence of adenosine triphosphate and luciferin fflux is able
to continuously express and generate an optical signal

10. CANCER:
• Cancer is the most common human genetic disease.
• The transition from a normal cell to a malignant cancer is
driven by changes to a cell's DNA which is known as
mutations.
• different types of cancer some of them includes
breast cancer, prostate cancer, skin cancer
DIAGNOSIS:
• presence of TKI-sensitizing somatic EGFR mutation in tumor tissue
strongly favors the diagnosis of lung cancer

11. • tumor markers for lung cancer , pancreatic cancer and breast cancer
is CA125,CEA
DOWNSYNDROME:
• is a genetic disorder caused by the presence of all or
part of a third copy of chromosome 21.
• I.Q level of children with down syndrome will be 50
• extra genetic material present in Down syndrome
results in overexpression of a portion of the 310 genes located on
chromosome 21and region is located at bands 21q22.1–q22.3
DIAGNOSIS:
• diagonised by fluorescent in situ hybdrization (FISH) and PCR
technique

12. • Primers for the analysis of chromosome 21 have been developed and
the D21S11 gene on chromosome 21 could be used for the target of
PCR
• lee et.al termed the homologous gene quantitative polymerase chain
reaction (HGQ-PCR) which uses one pair of primers.
• can directly identify the additional copy of chromosome 21 by
simultaneously amplifying two highly homologous genes of the
human liver-type phosphofructokinase located on chromosome 21
(PFKL-CH21) and the human muscle-type phosphofructokinase
located on chromosome 1 (PFKM-CH1).