Gentic Markers

8/8/2019 Gentic Markers

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Learning Objectives:Define genetic markersRecognize medicolegal importance of geneticmarkers

Classify different genetic markersDescribe genetic markers on inheritance basesApply genetic markers to solve crimes andcases of disputed paternity

Be aware of the hazards of blood transfusion



Genetic Markers:Unique factors in human blood used todiscriminate him from all other persons

Genetic Markers used in Disputed Parentage Testing

І- Blood Group Systems.ІІ- Serum Protein Systems .ІІІ- Red Cell Isoenzymes System.ІV- Hemoglobin Variants.V- Major Histocompatibility complex. HLAVІ- DNA Polymorphism.



Medicolegal importance of genetic markers

Identification:Paternity Problem:

Medical fieldSemen grouping.

grouping.saliva groupingsaliva g

rouping



Medicolegal importance of genetic markers

1. Identification:** Source of blood (murder).

Blood or not

A presumptive chemical test.Confirm (M.P) of heme- crystallineBlood group

DNA



** Massdisaster

****kidnapping caseskidnapping cases

fitting together human parts

alleged mix-up of infants



2- Paternity Problem: Disputes may arise under the following circumstances:

????????

1- When a man is accused of being the father of a childin rape and claims that he is not the father of a child.

2- When a man claims to be the father of a child but themother denies the claim.

3- A married man may allege that his wife has committedadultery, and that he is not the father of one or more of her children



3 - Medical field1- Before:Blood transfusion.

organ transplantation.

2- Rh –ve female2- Rh –ve female A pregnant Rh - veA pregnant Rh - ve femalefemale

should be givenshould be given IGIG at labor toat labor toprevent erythroblastosisprevent erythroblastosisfetalis in the next child.fetalis in the next child.

33 -The association-The association between certain blood groups andbetween certain blood groups anddiseasesdiseases duodenal ulcer duodenal ulcer is moreis more

common in persons of bloodcommon in persons of blood groupgroupO.O.



2-resumptive test for semen

Phosphatase (AP) Test

groupinggrouping

In cases of sexual assaultsIn cases of sexual assaults

11--laser lightlaser lightto locate suspected semento locate suspected semen

33--visualize spermatozoavisualize spermatozoaThe average ejaculate containsThe average ejaculate contains

5050to 150 million sperm cells per mLto 150 million sperm cells per mL

44--The presence of the prostate-specific antigen P30The presence of the prostate-specific antigen P30



Medico legal Problems :a man who has a (oligospermia) who has aspermia.phosphate test indicates the presence of semen,But the microscopical analysis yields no detectablespermatozoa.

Confirm by the presence of a protein, P30.

prostate specific antigen (PSA) ,found in high concentration in human semen.Some laboratories even use P30 testing in place of MP for semen identification.



5 - saliva grouping :Cigarette buttsDental floss

Tooth picksChewing gumDental applicationsHuman bitesIn cheese or appleSaliva on envelope and postage stamps

arealso helpful for grouping.



I. Blood group systemsABO groupsRh groupMN system.

Other blood groups.II. Red blood cell enzymesIII. Serum proteinsIV. Hemoglobin variantsV. HLA system.VI.DNA

Genetic Markers



I. Blood group systems

1. ABO groupsThe identification of blood groupA, B, AB or O is based on

appearance or absence of antigens and antibodies .



Where ?1- In blood2 - Other tissue cells and in body:sweat, tears, bile and milk. (secretors)



2-Rh group

Rh n e g a tive

Rh positive

blood transfusion

in the obstetric field.NBindependent of sex3 alleles in 2 alternative forms C, c , D, d , E ,e. + variant is determinedby presence of D.





II. Red blood cell enzymes

Phosphoglucomutase (PGM)3 phenotypes : PGM 1, PGM 2, PGM 1-2Adenylate kinase .Acid phosphatase.These could be used for blood stains, in

body

fluids, in hair root and in teeth pulp.

These iso enzymes could be demonstratedusing gel electrophoresis.



III. Serum proteins

Haptoglobin : Hp3 phenotypes: Hp1, Hp2,

Hp1-2Group specific component

GcImmunoglobulins: Gm, KmTransferrin Tf

Electrophoresis





TYPES1- Adult haemoglobin Hb A

- Makes up about 95% - 98% of HbFound in adults.Contains 2 (α) protein chains

2 (β) protein chains.



2- Fetal haemoglobin Hb F

a fetal nucle ated erythrocytea fetal nucleated erythrocyteby fluorescenceby fluorescence

Makes up to 2% of HbFound in adults.has 2 (α) and 2 (γ) protein chains.

The primary hemoglobin produced by the fetusduring pregnancy . usually falls to a low levelshortly after birth.



3-Sickle cell hemoglobin Hb S.

Has a single amino acid substitution inthe β-globin chain

from glutamic acid to valine



Defintion

a substance that is located on the surface ofWBCs lymphocytes and varioustissues.

They are of 2 classes:Class I : HLA-A, HLA-B, HLA-C.

Class II : HLA-D, HLA-DR, HLA-DQ.

This substance plays an important role in thebody's immune response.

V. HLA systemV. HLA system



Medicolegal importantance:

1- In determination of the degree of tissuecompatibility between transplant recipients anddonors to diminish rejection after transplant.

2- HLA can aid in paternity exclusion testing .

3- Certain HLA types have been linked toautoimmune disorders as rheumatoid arthritis ,

multiple sclerosis, serum lupus erythematosus,

http://medical-dictionary.thefreedictionary.com/Autoimmune+Disorders

http://medical-dictionary.thefreedictionary.com/Rheumatoid+Arthritis

http://medical-dictionary.thefreedictionary.com/Rheumatoid+Arthritis

http://medical-dictionary.thefreedictionary.com/Autoimmune+Disorders



Principles of blood group inheritancePrinciples of blood group inheritance

If one parent has a homozygous allelicpair then that gene must be present inall of his or her offspring.

HH hh

Hh Hh Hh Hh

1-Constant throughout life.

2-Ag pass from parent to offspring

3-One from each parent.

4-Donate at random.



Inheritance of blood groups ABO groups:There are 3 alleles A : A A - A a B : BB- Bb O : OO

Father AB

A B

Mother O

O O

Ao Ao Bo Bo







Exclusion of paternity1- By finding a gene product in a child :absent from both mother and putative

father e.g. mother O and father O andchild A.

A

OO



2- By finding a gene which the putative father must give to his offspring do not appear inthe child:When the father is homozygous for a genewhich does not appear in child.

e.g. father M and child N.

NN

MM



3- When the father is heterozygous for 2 genes neither appear in child

e.g. father AB and child O.

AB

OO



22..Inheritance of HLAInheritance of HLA

Inheritance of HLA.Each childinherits 2 HLA-A and 2 HLA-B,one from eachparent. HLA has

a greatindividualizingpotential indisputedpaternity.





Four types of bases:

consisting of :two purines,adenine (A).guanine(G).

two pyrimidines.cytosine (C).thymine (T).

NB

In RNA uracil (U) replacesthymine

Every cell within an individual containsthe same DNA





Paternity tests:1- Good negative.

using different blood markers require a greatnumber of blood test and could only provethat an individual was not the father of a

child.

2- Good positive

DNA finger printing alone good positive showwhether or not a man is the biological fatherof a child.





Hazards of blood transfusion A. Immediate reactions:

1- Febrile reactions:Due to pyrogens, leukocyte

isoagglutininor platelet agglutinins.

Pyrexia1- multiple transfusions.2- haemolytic reactions.3- infected blood.2. Allergic reactions:Skin rashantigen and antibody.

3. Circulatory overload:Leading to heart failure.

44..Reactions due to infected blood Reactions due to infected blood ::

5 5 ..ThrombophlebitisThrombophlebitis::More common after cannulationMore common after cannulation..

6 6 ..Citrate toxicity Citrate toxicity ::hypocalcaemiahypocalcaemiahyperkalaemiahyperkalaemia..

HypotensionHypotensionarrhythmiaarrhythmia..



B. Delayed reactions:1. Haemolytic reactions:

S&S jaundice and haemoglobinuria.due to Blood group incompatibility,Improper storage of bloodTransfusion of haemolysed blood (over heated – freezed).2. Immunological sensitization a red cell antigen - production of immune antibodies to

that antigen e.g. Rh negative.

This is harmful in patients needing multiple transfusions.3.Transfusion siderosis.4. Transmission of diseases:Hepatitis B ,C. AIDS, Malaria, Cytomegalovirus



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Gentic Markers