Genetics in Transfusion Medicine PDF

Faculty of Health Sciences Diploma in Medical Laboratory Technology CSI204 TRANSFUSION MEDICINE I Topic 3: Genetic Principles in Transfusion Medicine No...

Faculty of Health Sciences Diploma in Medical Laboratory Technology CSI204 TRANSFUSION MEDICINE I Topic 3: Genetic Principles in Transfusion Medicine Nor Raihan Mohammad Shabani, PhD Faculty of Health Science, UiTM Cawangan Pulau Pinang, Kampus Bertam 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 1 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 2  By the end of the topic, you should be able to: Define the following terms: chromosomes gene locus allele Lesson plan silent gene phenotype genotype homozygous heterozygous cis and trans positions autosomal dominant and recessive 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 3  Genetics Genetics is the scientific study of genes and heredity of how certain traits are passed from parents to offspring as a result of changes in DNA sequence. The genetic information is carried on double strands of DNA called chromosomes. 10/27/2023 Prepared by Nor Raihan Mohammad Shabani 4 Chromosome Chromosome is unit of inheritance that carries genes. A human somatic cell contains 46 chromosomes, that make up 23 pairs, deriving each chromosome from one parent 22 pairs of autosomes and 1 pair of sex chromosomes 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 5 Gene A gene is a segment of DNA that encodes a particular protein. It contains instructions for building one or more molecules that help the body work. It is the basic unit of inheritance of any trait, including blood group antigens They are found in specific places (loci) along the chromosomes DNA DNA consists of deoxyribose, the purine bases adenine and guanine, and the pyrimidine bases thymine and cytosine. The strands of DNA are held together by specific pairings of the bases (AT; GC). The double-stranded DNA twisted around each other to form the classic double-helix configuration. Locus Location of a gene at a specific place along a chromosome  Allele: An alternate choice of genes at a locus (e.g. P or P; a or a, B or b) Zygosity Zygosity describes the similarity or dissimilarity of genes at an allelic position on two homologous chromosomes Homozygous: involves inheritance of identical genes at a chromosomal locus (e.g. KK or kk at the Kell locus) Heterozygous: involves inheritance of two different genes at a chromosomal locus (e.g. Kk at the Kell locus) 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 12 Dosage A condition where a gene expression is stronger due to homozygosity (e.g. M+N-; Fya+Fyb-) RBC antigen system displaying dosage: Rh Lewis MNS Kidd (Jk) Duffy (Fy) Dominant and Co-dominant Dominant The expressed characteristic on one chromosome takes superior over the characteristic determined on the other chromosome e.g. A/O types as A or D/d types as D Co-dominant: equal expression of two different inherited alleles. Most blood group genes produce codominant traits - neither is dominant over the other (e.g. A/B types as AB) In co-dominance, both alleles are expressed, and their gene products are seen at the phenotypic level. 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 14  Recessive: the characteristic determined by the allele will only be expressed if the same allele is on the other chromosome also (e.g. can type as O only when the genotype is O/O or D negative when the genotype is d/d) Silent gene (amorphic gene): A gene that does not produce a serologically detectable product e.g. the O, d or h gene Genetic Inheritance of the ABO blood group Described by Bernstein in 1924 An individual's ABO type is determined by the inheritance of 1 of 3 alleles (A, B, or O) from each parent. Each individual inherits one ABO gene from each parent ABO blood types are inherited through genes on the long arm of chromosome 9 and they do not change as a result of environmental influences during life. 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 17 9q34 is the location, or locus of the ABO gene, which codes for the ABO blood group Phenotype versus Genotype Phenotype Genotype The result of the reaction between The genetic makeup and can be the red cells and antisera predicted using the phenotype and by considering the race of an individual Observable expression of inherited Actual genetic information for a traits (e.g. group A or Rh positive) trait carried on each chromosome (e.g. O/O or A/O). Often can be determined only by family studies 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 19  Individuals who have an AO genotype will PARENT A B O have an A phenotype. ALLELES People who are type O have an OO A AA AB AO genotype. In other words, they inherited a recessive O allele from both parents. (A) (AB) (A) The A and B alleles are B AB BB BO codominant. Therefore, if an A is inherited (AB) (B) (B) from one parent and a B from the other, O AO BO OO the phenotype will be AB. (A) (B) (O) Offspring genotypes are shown in blue. Phenotypes are red. 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 21 Summary of Blood group, Red cell antigens and the possible inherited genotypes. Human Red cell Serum Possible Blood group antigens antibodies Genotypes A A antigen Anti-B AA or AO B B antigen Anti-A BB or BO O None Anti A and OO only Anti-B AB A and B None AB only antigens  A/A A/O Homozygous A Heterozygous A Phenotype A Phenotype A Genotype A/A Genotype A/0 Can Contribute Only an A Can Contribute A or O Gene Gene to Offspring to Offspring 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 23 The 2 antigens responsible for the ABO groups are A and B which are the products of 2 allelic gene A and B. The 3rd allele at the A/B locus results in the absence of A or B. This allele, called O, is an amorph and people who inherit it from both parents are group O. Group A people : genotype AA, AO Group B people : genotype BB, BO Group O people : genotype OO 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 24 Cis and Trans position Trans position Cis position When two genes are inherited on When two genes are inherited on different chromosomes, they are the same chromosomes, their describe as trans relationship to each other is cis The concept of cis and trans is related to the Rh blood group system; when C is trans (on the opposite chromosome) to the D gene, the amount of D antigen 27/10/2023 produced Prepared by Nor will be depressed. Raihan Mohammad Shabani 25 Position Effect C trans-position effect; The D gene is in trans to the C gene, eg., C and D are on OPPOSITE sides: Dce/dCe C and D antigen arrangement causes steric hindrance which results in weakening or suppression of D expression. 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 26 Cis and Trans position Trans position Cis position Inheritance of regular ABO for AB Cis AB inheritance: in the AB & O parents parent, one allele is AB and other is O 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 27 Summary Blood group antigens are inherited characteristics. Each individual receives a combination of antigens from his or her parents. 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 28  By the end of the topic, you should be able to: Define the following terms: chromosomes gene locus allele silent gene Lesson plan phenotype genotype homozygous heterozygous cis and trans positions autosomal dominant and recessive 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 29 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 30 27/10/2023 Prepared by Nor Raihan Mohammad Shabani 31