3. IMHM 321 LEC- prelim L3 (review of important genetic principles as applied to blood banking) based on discussion.pdf

IMMUNO HEMATOLOGY (LECTURE) Quitaleg, Jenny Rose Maghuyop LEC PRELIM 3 REVIEW OF IMPORTANT GENETIC PRINCIPLES AS APPLIED TO BLOOD BANKING OUTLINE...

IMMUNO HEMATOLOGY (LECTURE) Quitaleg, Jenny Rose Maghuyop LEC PRELIM 3 REVIEW OF IMPORTANT GENETIC PRINCIPLES AS APPLIED TO BLOOD BANKING OUTLINE I. GENETICS I. Genetics II. Blood Group Systems  Study of inheritance or the transmission of III. International Society Of Blood characteristics from parents to offspring Transfusion (ISBT)  It is based on the biochemical structure of chromatin, IV. Genetics which includes nucleic acids and the structural proteins V. Mendel’s Law Of Inheritance that constitute the genetic material as well as various VI. Genetics enzymes necessary to understand the different heredity, VII. ABO Genotypes & Phenotypes principles of modern blood banking VIII. Term Used In Blood Bank IX. Dosage Effect X. Term Used In Blood Bank – Genotype of an individual genetics XI. Inheritance Patterns – Not visible characteristics genotypic XII. Null Phenotypes – Information written from our characteristics DNA – Observable characteristics Phenotypic characteristics CENTRAL DOGMA OF DNA DNA  RNA  Protein  Function DNA long strand of DNA located in the nucleus organized into chromosomes has written information: genotypic characteristics only ↓ TRANSCRIPTION written information from the DNA is copied to mRNA mRNA will go to ribosome ↓ TRANSLATION the written information or DNA carried by mRNA will be coded as protein by the ribosome protein now will have a function based on what is written on the DNA Page 1 of 8  location of genes chromosome ABO ANTIGENS specific location of gene on locus a chromosome mainly made up of enzymes antigens transfer the antigens to the transferase enzyme  Required ABO genes to be produced RBC membrane once condense will become DNA chromosome ABO GENES  Located inside the long arm of chromosome 9 MODERN BLOOD BANKING  Deals with different blood group system III. INTERNATIONAL SOCIETY OF BLOOD o how blood group systems are being passed through TRANSFUSION (ISBT) generation o how different antigens is inherited from parents to offspring TRANSFUSION MEDICINE  Rely on understanding blood group genetics II. BLOOD GROUP SYSTEMS  Group of related red cell antigens which is similar in terms of biochemical structure, location in RBC, serologic properties and genetic control of antigen expression o it requires a gene to produce a certain antigen  Number assigned on each blood group system is based on the chronological order of discovery  Depends on the DNA of an individual what part of blood group system will be inherited from parents ABO BLOOD GROUP SYSTEM  ABO discovered 1901 by Karl Landsteiner  If an individual does not have CD36, when expose to ABO will produce antibodies against it  Related to parents - even though not the same but is related ABO CD36 first to discover last to discover ISBT 1 ISBT 45 each gene produces different products = different blood considered an antigen group system Page 2 of 8  1st Generation First-filial Second-filial IV. GENETICS generation generation synonym “Parental” second generation third generation crossbreed of crossbreed of homozygous red first-filial Genes – basic unit of inheritance and homozygous generation – located on different parts of chromosome, white flower specific part chromosome crossbreed allows usually 1 – encode for certain trait or visible possible possible characteristics combination combination – linear arrangement inside the nucleus – – either heterozygous seen homozygous on first filial condense when they will form chromosome dominant or generation Chromosomes – structure recessive within the 2 Types – or heterozygous nucleus that dominant or contains the recessive DNA somatic / 22 first generation + first filial generation = – linear autosomes PAIRS crossbreed of the parental type (44) limited gene combination structure of gene long no cell sex 1 PAIR strand division chromosome (2) XX, of DNA XY x– cell total 23 shaped division chromosome PAIRS 46 PHYLOGENETICS STUDY  track specific part of gene that is being pass through generation  track ancestors LAW OF INDEPENDENT ASSORTMENT V. MENDEL’S LAW OF INHERITANCE  second law of inheritance  members of one gene pair separate from one another GREGOR MENDEL independently of the member of other gene pairs.  states that “genes for different traits are inherited separately from each other”  Father of genetics  Postulated that offspring are combination of two different First-filial generation synonym second generation sets of genes – chromosome becomes separated  Describe the law of inheritance – multiple possible gene combination  Studied the inheritance from pea plant – first law of inheritance is based on this LAW OF INDEPENDENT SEGREGATION  was based from pea plant  first law of inheritance Page 3 of 8  Law of Independent Segregation and Law of Independent ABO Assortment differs on first filial aka second generation  present on red cell  observable VI. GENETICS  produce by the information from the DNA or the genotype Genotype – actual set of genes inherited from to be parents/actual genetic make-up of an expressed individuals – information written on chromosome particularly A dominant homozygous or A1A – A will be heterozygous A1O expressed on the gene that is inherited by generations – O will not be – characteristics not observable– must be encoded first to become observable expressed – predict the phenotype of an individual B dominant homozygous or BB – B will be – set of alleles of a given trait that is being heterozygous BO expressed carried by an organism – O will not be – needs to be expressed to become phenotype expressed Phenotype – physical or observable expression of inherited O recessive homozygous – doesn’t contain genes antigens – no product at all Punett – square used to calculate the frequency of the square – to have this blood resulting genotypes and phenotypes among type , you must be the offspring of a cross homozygous O – test to determine the possible gene only combination to be produce by mixing to different combination of genes – tells percentage and possibility for you to have that gene PUNETT SQUARE VII. ABO GENOTYPES & PHENOTYPES EXAMPLE 1  FATHER: A1A1 A1 A1 ABO BLOOD GROUP / POSSIBLE GENOTYPES A1 A1A1 A1A1 PHENOTYPE  MOTHER: A1B B A1B A1B A1 A1A1, A1O, A1A2 A2 A2A2, A2O B BB,BO A1B A1B 1. Probability that child’s genotype is A1A1: 50% A2B A2B 2. Probability that child’s phenotype is A1: 0% O OO 3. Probability that child’s blood type is A1B: 50% EXAMPLE 2  FATHER: A1O A1 O  MOTHER: BO B A1B BO O A1O OO 1. Probability that child’s genotype is A1B: 25% 2. Probability that child’s phenotype is BO: 25% 3. Probability that child’s blood type is A1O: 25% To know the genotype: 4. Probability that child’s blood type is OO: 25% – must first know whether a particular antigen is dominant or recessive Page 4 of 8  VIII. TERM USED IN BLOOD BANK STRONGER AGGLUTINATION WEAKER AGGLUTINATION produced by antigens that are produced by antigens expressed by homozygous expressed by heterozygous alleles – one of two or more genes that express a genes genes given trait red cell from the homozygous – present on chromosomes individual possess more antigen – part of the gene that produce antigens or trait MNSs blood group system – located at the locus – portion of the chromosome that codes homozygous M gene: MM for a certain trait or gene – has more antigen antithetical – term used to refer to the opposite gene present on red cell – if a particular antigen is produced, other – anti M shoes stronger gene will inhibit its production reaction polymorphic – genetic system that expresses multiple gene products heterozygous M and N gene: – single gene produces multiple antigens MN MHC genes – fewer amount of Rh blood group system antigen present on dominant gene – gene whose product is always expressed red cell – as long as the allele is there it will be – weaker reaction expressed whether it is heterozygous or – anti M added shows homozygous dosage effect recessive gene – gene whose product is only expressed when inherited in a homozygous way – if both allele are recessive it will be expressed codominant – genes whose products are both genes expressed – both dominant alleles will be expressed homozygous – both genes for a given trait are the same genes – same gene combination heterozygous – genes for a given trait are different genes – combination of two different genes RH BLOOD GROUP SYSTEM X. TERM USED IN BLOOD BANK Blood type Rh factor Rh positive Positive Rh negative Negative CIS TRANS – 2 genes are on the – 2 genes are on the Rh O Negative same side of the different side of the chromosome chromosome – support each other = – antithetical D antigen is the most immunogenic stronger reaction – inhibit each other – does not have any problem at all AB AB ab Ab IX. DOSAGE EFFECT  quantity of antigens on the red cells blood group system that show dosage effect: KIDD, DUFFY, RH, MNSs blood group system blood group system that show variable dosage effect: Lutheran blood group system blood group system that does not show dosage effect: ABO blood group system Page 5 of 8  LINKED GENES HAPLOTYPE XI. INHERITANCE PATTERNS – 2 genes in the – linked set of genes that chromosome are very are inherited and close to each other expressed together – not on the exact same location but are near ABO Inheritance Patterns each other on the locus Parental blood groups Child's blood group – locus adjacent on each O and O O other – inherited in one type O and A O or A of combination O and B O or B ABO D, c, and e genes when O and AB A or B D,c,e if inherited will produce expressed will result to DCE A and A A or O Rh antigen Rh blood type A and B O or A or B or AB A and AB A or B or AB B and B O or B B and AB B or A or AB AB and AB A or B or AB A B O A AA AB AO B AB BB BO O AO BO OO no h antigen = no ABO AUTOSOMAL DOMINANT INHERITANCE  All the members of a family that carry the allele show the physical characteristic  Generally, each individual with the trait has at least one parent with the trait  Familial disease, either homozygous or heterozygous will be seen in phenotypic level Autosomal – product of the gene will always be dominant expressed – heterozygous still expressed – familial disease - either homozygous or heterozygous will be seen in phenotypic level Autosomal – product of the gene will only expressed if recessive homozygous – requires to be homozygous to be expressed – will be silent gene if inherited heterozygously Sex-linked – father to daughter transmission of trait dominant Sex-linked – mother to son transmission of trait recessive Codominant – equal expression of inherited alleles/genes – both dominant allele was inherited both will be expressed autosomal trait - trait that are not carried on the sex chromosome , present on autosome Page 6 of 8  AUTOSOMAL RECESSIVE INHERITANCE X-LINKED RECESSIVE INHERITANCE  A recessive trait is carried by either parent or both parents  The father always expresses the trait but never passes but is not generally seen at the phenotypic level unless it on to his sons. both parents carry the trait.  The father always passes the trait to all his daughters,  In some cases a recessive trait can be genetically who are then carriers of the trait. expressed in a heterozygous individual but is often not  With an X-linked recessive trait, a disease-carrying gene seen at the phenotypic level can be passed from generation to generation with many individuals not affected. SEX CHROMOSOME XX XY gender female male X received from father and mother received from mother X-LINKED DOMINANT INHERITANCE  If the father carries the trait on his X chromosome, he XII. NULL PHENOTYPES has no sons with the trait, but all his daughters will have the trait.  Women can be either homozygous or heterozygous for an X- linked trait.  Phenotypes that lack the expression of the red cell antigens of a particular blood group systems.  Genes that do not produce any products at all MAY BE DUE TO INHERITANCE OF: 1. Silent / Amorphic gene that expresses no gene: product 2. Regulator/Suppressor gene that inhibits the gene: expression of another gene Page 7 of 8  Rh null silent gene positive phenotype D gene / / X Co – / X expressor: X1r Suppressor: x / Xor D antigen will be will not be no product produce produce at all what glycoprotein does Rh gene Rh associated need in order to be express? glycoprotein what codes for Rh associated X1r glycoprotein? silent or suppressor gene produces null phenotype __________ Page 8 of 8