Blood group Blood group geneticsgenetics

By:-Dr. Nippun Prinja

Covered under 6 Covered under 6 headings:-headings:-1. Basic principles of Genetics2. Blood group gene mapping3. Blood group terminology4. Inheritance of genetic trait5. Population genetics6. Blood group genomics

1.)BASIC PRINCIPLES OF 1.)BASIC PRINCIPLES OF GENETICSGENETICS

• Chromosome-thread like structure visible during cell division, 23 pairs,4 types.

Gene -segment of dna present on chromosome at specific location(loci),basic unit of inheritence of any trait including blood group antigens that is passed from parents to offspring

• Alleles-gene at given locus of chromosome may exist in more than one form.eg:-ABO gene locus is considered to have 3 alleles A,B,O, with possible six genotypes(A/A,A/O,A/B,B/B,B/O,O/O)

• HOMOZYGOUS• HETEROZYGOUS• HEMIZYGOUS

• Genotype.• Phenotype.

• ANTIGEN DENSITY- quantity of antigen expressed (more seen in homozygous than in hetrozygous)

• DOSAGE EFFECT-homozygous red cells are more strongly reactive with antisera than heterozygous

• POLYMORPHISM- occurrence of allelic variation in genome mostly seen with Rh and MNS blood group system

• MUTATION-polymorphism that did not exist in biological parents OR difference in allele that lead to permanent change in DNA sequence.

2.)BLOOD GROUP GENE 2.)BLOOD GROUP GENE MAPPINGMAPPING

Gene locus is assigned by gene mapping.

Duffy BG was 1st to be assigned to a chromosome.

34 blood groups are assigned to their chromosomes.

Traditional methods:- G & Q bandingAdvance methods:-FISH & chromosome walking technique

3.)BLOOD GROUP 3.)BLOOD GROUP TERMINOLOGYTERMINOLOGY

In 1980 ISBT established this uniform nomenclature.

Each BG system has been given a particular alphanumeric terminology.

Each antigen is also given number

Terminology takes into account guidelines given by HUGO

4.)INHERITANCE OF GENETIC 4.)INHERITANCE OF GENETIC TRAITTRAITA)AUTOSOMAL DOMINANT

B)AUTOSOMAL RECESSIVE

C) SEX LINKED DOMINANT INHERITANCE

4)SEX LINKED RECESSIVE INHERITANCE

INDEPENDENT SEGREGATION-Sepration of homologous chromosomes .

INDEPENDENT ASSORTMENT-alleles are inherited independently from each other OR one allele inheritance does not influence another allele

LINKAGE-physical association between two genes located on same chromosome and inherited together.

(Eg:-RHD and RHCE antigens on chromosome 1) Linkage between Lutheran(lu) and ABH secretion was 1st recognized example of autosomal linkage in humans

CROSSING OVER-exchange of genetic material b/w homologous chromosome pairs .

5.)Population genetics5.)Population geneticsStudy of distribution pattern of genes.Uses- 1) phenotype prevelance 2)calculation of antigen negative phenotype 3)allele frequency

HARDY WEINBERG LAW

VALID IN STABLE AND LARGE POPULATION WHERE GENE FREQUENCIES REACH EQUILIBRIUM AND MATING IS RANDOM

Used for:-

1)estimation of frequency of particular alleles.

2)estimation of frequency of particular genotype.

APPLICATION IN BLOOD GROUP APPLICATION IN BLOOD GROUP GENETICSGENETICS

6.)BLOOD GROUP GENOMICS6.)BLOOD GROUP GENOMICS

HEMAGGLUTINATION HAS LIMITATIONSNEWER DNA TECHNIQUES(PCR,RFLP,GEL

ELECTROPHORESIS)

To predict phenotpe

1)After recent multiple transfusions.

2)distinguish an alloantibody from autoantibody

3)when patients red cells are coated with immunoglobulin

4)after allogenic stem cell transplantation

5)resolve discrepencies Eg:A B and Rh

6)mass screening to increase antigen negative population