Basic Genetics for Immunohematology PDF

MLS 323 LEC – Immunohematology Block Exclusive Notes BASIC GENETICS FOR IMMUNOHEMATOLOGY GENETICS Study of transmission of inherited characteristics Important in the study of antigen inheritance and inherited disorders Genetic material is c...

MLS 323 LEC – Immunohematology Block Exclusive Notes BASIC GENETICS FOR IMMUNOHEMATOLOGY GENETICS Study of transmission of inherited characteristics Important in the study of antigen inheritance and inherited disorders Genetic material is contained in chromosomes o Chromosomes Structures that carry genetic information encoded on double-stranded DNA o Deoxyribonucleic acid (DNA) The chemical basis of heredity and the carrier of genetic information for all organisms Double helix nucleic acid Bases: adenine (A), thymine (T), cytosine (C), and guanine (G) The normal number of human chromosomes consists of 46 in each nucleated cells Gene A unit of inheritance within a chromosome o Autosomal genes: genes expressed with equal frequency in males and females on a non-sex chromosome o Sex-linked genes: genes carried on the sex chromosome A segment of DNA arranged along the chromosome at a specific position called locus Genes at a specific locus that differs in their nucleotide sequences are called an allele o Alleles: alternate forms of a gene at a given locus o Gene locus: specific place on a chromosome where the genes or alleles are located Terms: Polymorphic, Allelic, and Antithetical o Polymorphic: Having two or more possible alleles at a locus o Allelic: Term to describe one of two or more different genes that may occupy a specific locus on a chromosome o Antithetical: Opposite form of a gene, different allele; opposite antigens encoded at the same locus Regulator and Suppressor o Regulator: Gene that produces a repressor substance that inhibits an operator gene o Suppressor: Gene that suppresses the phenotypic expression of another gene (especially of a mutant gene) Genotype and Phenotype o Genotype: Total genetic composition of an individual, representing maternally and paternally derived genes o Phenotype: Detectable or expressed characteristics of genes Dominant, Recessive and Codominant o Dominant: Only one allele must be inherited for it to be expressed; gene product is always present o Recessive: Gene that, in the presence of the dominant gene, is not expressed; the same allele must be inherited for it to be expressed o Codominant: Term used to describe a pair of genes in which neither is dominant over the other; that is, they are both expressed Mendelian Inheritance Principles Mendelian Genetics: Genes occur in pairs; one gene is passed from parent to offspring o Law of Independent Segregation Two members of a single gene pair passed from one generation to the next in separate genes o Law of Independent Assortment Traits inherited from different chromosomes expressed separately and discretely Inheritance Patterns o The inheritance of blood group antigens can be predicted using a Punnett square o Punnett squares are useful for understanding the inheritance of blood groups and ramifications of heterozygosity or homozygosity Homozygous: Individual inherits identical alleles at the same gene locus from both parents Heterozygous: Individual inherits different alleles at the same gene locus from each parent Dosage effect o Agglutination reactions are generally stronger for homozygous cells and slightly weaker for heterozygous cells o The presence of the homozygous genotype can express itself with more antigens than the heterozygous genotype Page 1 of 3 DISCLAIMER: This Block Exclusive Lecture Notes is intended ONLY for the use of MLS 323 Class Codes 8412, 8426, 8440, 8447, and 8461 of Academic Year 2023-2024. This handout shall NOT, by any means, replace the reference textbooks and modules as the principal sources of learning Immunohematology.  MLS 323 LEC – Immunohematology Block Exclusive Notes Position effect o Cis: Genes are inherited on the same chromosome Cis-position refers to the situation in which a gene on one chromosome of a homologous pair affects the actions of a related gene on the same chromosome o Trans: Genes are inherited on separate chromosomes Trans-position refers to the situation of having a gene on one chromosome of a homologous pair affect the actions of a related gene on the other homologue Linkage, haplotypes, and amorphs o Linkage genes: Genes that are close together on a chromosome and inherited as one unit o Haplotypes: Set of genes inherited via one of the two parental gametes o Amorphs: Genes that do not produce a detectable trait International Society of Blood Transfusion (ISBT) Terminology for Red Blood Cell Surface Antigens in Blood Group Systems ISBT System Chromosomal ISBT System Chromosomal System System Number Number Number Number 001 ABO 9 023 Indian 11 002 MNS 4 024 OK 19 003 P or P1PK 22 025 Raph 11 004 Rh 1 026 John Milton Hagen 15 005 Lutheran 19 027 I 6 006 Kell 7 028 Globoside 3 007 Lewis 19 029 Gill 9 008 Duffy 1 030 RHAG 6 009 Kidd 18 031 FORS 9 010 Diego 17 032 Jr 4 011 Cartwright 7 033 Lan 2 012 Xg X 034 Vel 1 013 Scianna 1 035 HRF/CD59 11 014 Dombrock 12 036 Augustine 6 015 Colton 7 037 Kanno 20 016 Landsteiner-Wiener 19 038 SID 17 017 Chido/Rodgers 6 039 CTL2 19 018 H 19 040 PEL 13 019 Kx X 041 MAM 19 020 Gerbich 2 042 EMM 4 021 Cromer 1 043 ABCC1 16 022 Knops 1 RELATIONSHIP TESTING Refers to the testing of genetic markers inherited to determine the presence or absence of a biological relationship Goals of Testing: o To confirm a specific biological relationship with the individual in question, usually a father or a mother or sometimes a sibling o To establish evidence in resolving medicolegal cases Types of Genetic Systems Used: 1. Red Blood Cell Antigens o Includes: ABO Blood Group System Kell Blood Group System Rh Blood Group System Duffy Blood Group System MNSs Blood Group System Kidd Blood Group System 2. Red Cell Enzymes and Serum Proteins o Enzymes: Phosphoglucomutase 1 (PGM1) Adenosine deaminase Acid Phosphatase (ACP) Adenylate kinase Esterase D (ESD) Alkaline phosphatase o Proteins: Haptoglobin (Hp) Group-specific component (Gc) Page 2 of 3 DISCLAIMER: This Block Exclusive Lecture Notes is intended ONLY for the use of MLS 323 Class Codes 8412, 8426, 8440, 8447, and 8461 of Academic Year 2023-2024. This handout shall NOT, by any means, replace the reference textbooks and modules as the principal sources of learning Immunohematology.  MLS 323 LEC – Immunohematology Block Exclusive Notes 3. Immunoglobulins o Three immunoglobulin chains demonstrate polymorphism Gamma heavy chain: Gm Alpha heavy chain: Am Kappa light chain: Km 4. Human Leukocytes Antigens (HLA) o HLA antigens follow Mendelian genetics principles and can be used to determine the parents of offspring HLA genes are polymorphic, with many alleles possible at each locus The more alleles, the less likely it is to find two identical individuals 5. DNA Testing o Permits the direct identification of the individual source because it is personal and manifests biological variation o DNA evidence is currently considered evidence of positive identification Interpretation of Results based on Blood Group Phenotype: o Blood group antigens, many of which are expressed as codominant traits with simple Mendelian modes of inheritance, are useful in parentage analyses. o If one assumes maternity and that test results are accurate, paternity can be excluded in either of two ways: 1. Direct Exclusion Direct exclusion of paternity is established when a genetic marker is present in the child but is absent from the mother and the alleged father Occurs when: o a marker is detected in the child, whereas it is absent in the mother and the alleged father o the alleged father’s phenotype demonstrates two markers, and the child has neither one of them Example: Child Mother Alleged Father B O O Based on the phenotypes of mother and child, the B gene must have been inherited from the biological father and is called a paternal obligatory gene False direct exclusion: o Result of mutations that are significant enough to alter the final product o Lack of precursor substance o Suppressor activity at a locus unlinked to the one tested o Chimeric state of one of the tested individuals 2. Indirect Exclusion Exclusion is indirect when the child lacks a genetic marker that the alleged father (given his observed phenotype) must transmit to his offspring Occurs when a single marker is detected in the child, and a different single marker is detected in the alleged father Example: Child Mother Alleged Father Jk(a+ b–) Jk(a+ b–) Jk(a– b+) False indirect exclusion: o Occur secondary to the presence of silent alleles o Note: Interpretation of phenotypic data must take into account all biologic and analytic factors known to influence results. Interpretation of Results on a Classic Trio: Mother, Child, and the Alleged Father o Results are first analyzed to determine whether the alleged father is excluded as the biological father o If he is not excluded, a statistical analysis is performed to determine his relative probability of being the biological father of the child as compared to a random man unrelated to him or the mother o When the alleged father cannot be excluded from paternity, it is possible to calculate the probability of paternity The probability that the alleged father transmitted the paternal obligatory genes is compared with the probability that any other randomly selected man from the same ethnic/ racial population could have transmitted the genes The result is expressed as a likelihood ratio (paternity index) or as a percentage o Methods for parentage analysis often include the study of many genetic systems other than RBC blood groups Many parentage testing laboratories employ the STR method of DNA analysis as a means of evaluating cases of disputed parentage o The AABB has developed standards for laboratories that perform parentage studies Page 3 of 3 DISCLAIMER: This Block Exclusive Lecture Notes is intended ONLY for the use of MLS 323 Class Codes 8426 and 8433 of Academic Year 2022-2023. This handout shall NOT, by any means, replace the reference textbooks as the principal source of learning Immunohematology.