CLS 3311 Advanced Clinical Immunohematology

1. CLS 3311Advanced Clinical Immunohematology Course Orientation and GENETICS LECTURE

2. Just a word about Transfusion Medicine, aka Blood Bank and your role as a Clinical Laboratory Scientist.

3. I would like to introduce you to my youngest son, Jacob Daniel Zundel.

4. My son was ‘overt breech’ when he decided to enter the world which means that the first act he did in this life was to ‘MOON’ both his mother and myself. • When he finally did enter the world he was not breathing or showing any signs of life. Within approximately 1 minute he screamed but was having some significant problems. • He had tachypnea, pulmonary hypertension, etc. He spent the first ten days of his life in the hospital with ALL of the health care team involved in preserving his life.

5. Clinical Laboratory Scientist • As a CLS you will participate in saving many lives every day you are on the job. • The next slide is a photo that was taken when Jacob required a transfusion of red blood cells. • A CLS performed all the necessary testing on both my wife and my son to insure the safety of the blood that you see saving his life.

6. The red arrow indicates the red blood cell transfusion line.

7. As a result of the hard work of Clinical Laboratory Scientist’s, Nurses, Respiratory Care, Radiology, and neonatal Physicians Jacob came home happy and healthy. I am sure that you or someone you love has had to spend some time in the hospital and has had laboratory work performed on their blood. It is important that you remember that every patient’s specimen and sample is from someone’s son or daughter, mom or dad, brother or sister. It may even be YOURS!!

8. I show you these images because it is not often that we see the results of our labors in the Blood Bank. I suggest that you take the time to occasionally follow the blood you crossmatch and see who gets it, whose life you saved that day. Don’t be intrusive, just hang back and feel the joy of a job well done!

9. Blood Bank Genetics • Genetics is the study of inheritance! • Inheritance of transmissible characteristics or ‘traits’: such as blood group antigens found on red blood cells • Specific regions of the chromosome (GENES) encode the information for specific traits. • Humans have 46 chromosomes, which are present in 23 pairs-one member of each pair is inherited from each parent

10. Traits are the observed expressions of genes. • Each gene codes for the production of a specific protein by coding for a sequence of amino acids or polypeptides. • These proteins may function alone as a single antigen or they may combine with other proteins, lipids or polysaccharides to form more complex antigens. • The K1 (Kell) gene codes for the production of the K1 antigen present on the red blood cell membrane.

11. What are RBC Antigens? What are Soluble blood group substances (antigens)? Each gene codes for the production of a _____________. Structures imbedded in or protruding from the rbc membrane Antigens found in body fluids (plasma, saliva, etc.) Specific protein Gene Products

12. Alternate form of a gene at a specific locus is an ________. What is a Silent Allele? What is Co-Dominant (dominant) Inheritance? Allele: Alleles in the ABO blood group are A, B and O Amorph: no detectable gene product: O gene has no detectable product. Observable traits when inherited. Inherit A and B genes = A and B antigens are present Gene Interactions

13. What is Homozygous? What is Heterozygous? Inheritance of identical alleles at a given locus on both chromosomes: A/A or B/B Inheritance of different alleles at a given locus on both chromosomes: A/O, B/O or A/B Each individual has at least two alleles: One on each chromosome.

14. What is Genotype? What is Phenotype? Genetic make-up of an individual: genes determine which blood group antigens are present on the rbc membrane. A/O is a genotype. Outward expression of genes: Observable traits. Blood group antigen typing indicates a persons phenotype. Group A is a phenotype. Genotype vs. Phenotype

15. What are the possible genotypes for a Mom who phenotypes as a Group A? • What are the possible genotypes of a Dad that phenotypes as a Group B? • What are the possible genotypes and phenotypes that result from the mating of a Group A mom and a Group B dad?

16. Mom: A/O, Dad: B/B Mom: A/A, Dad: B/O Mom: A/O Dad: B/O Mom:A/A, Dad: B/B A O A O B A/B B/O B A/B B/O A/O O/O B A/B B/O O A A A A B A/B A/B B A/B A/B B A/B A/B O A/O A/O

17. DOSAGE • In some blood group systems, persons homozygous for an allele have MOREantigen on their red cells than persons heterozygous for an allele. • Variation in antigen expression due to the number of alleles present is called DOSAGE • Dosage effect is not seen with all blood group antigens or even with all antibodies of a given specificity. • Blood groups that demonstrate dosage include: Rh, Duffy, MNSs, and KIDD.

18. Dosage: Heterozygous expression demonstrates weaker reaction with reagent antisera, such as anti-Jka. Fewer Jka antigens present on RBC membrane. Jkb Jkb Jkb Jka Jka Jka Jkb Jka Jka Jkb Jkb Jka Jka Jkb Jka Jka Dosage: Homozygous expression demonstrates stronger reaction with reagent antisera, such as anti-Jka. More Jka antigens present on RBC membrane. Jka Jka Jka Jka Jka Jka Jka Jka Jka Jka Jka Jka

19. Gene Frequencies • Frequency of a gene in a certain population. For example, what is the prevalence of the R1r Rh haplotype in the white population in America? • We do NOT directly measure the prevalence of a gene in a certain population. But we do measure the frequency of the gene product - in this case, blood group antigens.

20. Gene Frequencies • Gene Frequencies can only be extrapolated from population studies using phenotype frequencies. (ABO Table 5-3, page 95) • Traits are the outward expression of genes. • From phenotype frequencies we can predict the most likely genotype of a person. • Some gene frequencies cannot be determined serologically - Why?