L02 - Introduction to Basic Genetics PDF

9/20/2024 Chapter 2: Basic Genetics Preamble ▪ PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. ▪ PowerPoints DO NOT cover the details needed for the Unit exam ▪ Each student is responsible for READING the TEXTBOOK for details to...

9/20/2024 Chapter 2: Basic Genetics Preamble ▪ PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. ▪ PowerPoints DO NOT cover the details needed for the Unit exam ▪ Each student is responsible for READING the TEXTBOOK for details to answer the UNIT OBJECTIVES ▪ Unit Objectives are your study guide (not this PowerPoint) ▪ Test questions cover the details of UNIT OBJECTIVES found only in your Textbook! 1  9/20/2024 Introduction ▪ Many areas of transfusion medicine rely on an understanding of blood group genetics and accurate and sensitive methods of pathogen testing to keep the blood supply safe. ▪ Most of the antigens in the various blood group systems generally follow straightforward inheritance patterns, usually of a codominant nature. Classic Genetics ▪ Genetics is concerned with ▪ the biochemical and biophysical nature of nucleic acids ▪ population studies and epidemiology ▪ understanding of inheritance patterns ▪ provide insight on antigen-typing discrepancies due to weakened or variant alleles 2  9/20/2024 DEFINITIONS  Genetic information is carried on chromosomes  Gene – is unit of inheritance coding  Genes – subunit of chromosome  Genes – found along the chromosome at places called loci (location)  Example: ABO group on chromosome 9 and Rh group on chromosome 1 DEFINITIONS  Alleles – alternate forms of a gene at a given locus  Amorph – “silent” gene (no gene product is produced)  Codominant – alleles that are both expressed in heterozygous state  Example: AB blood group  Genotype – total genetic makeup, both expressed and unexpressed genes  Phenotype – observable produce of the genes at a given locus  Example: A/O or A/A can be genotype but both will be A as phenotype 3  9/20/2024 DEFINITIONS  Cis position – when the loci that the genes occupy are on the same chromosome.  Trans position – the location of two or more genes on opposite chromosomes of a homologous pair  Example DCe/DcE  C = cis position to e (Same side of chromosome)  C = trans position to E (Opposite side of chromosome) DEFINITIONS  Heterozygous – different alleles at a given locus on a pair of chromosomes. Sometimes known as a single dose (AO or Kk)  Homozygous – identical alleles o at a given locus on a pair of chromosomes Sometimes known as a double dose (AA; KK or kk)  Recessive – allele expressed in homozygous state, masked by dominant allele 4  9/20/2024 DEFINITIONS  Dosage – phenomenon where an antibody reacts more strongly with a red cell carrying a double dose rather than a single dose  Public Antigen – found on RBC’s of greater than 98% of population  Private Antigen – found on RBC’s of less than 1% of population  Autosome – any chromosome other than the sex chromosomes (X and Y) Population Genetics ▪ The major areas of population genetics of concern to blood banking include ▪ Pioneering work of Linnaeus and Darwin ▪ Mendel’s Laws of Inheritance ▪ Hardy-Weinberg Principle ▪ Inheritance patterns 5  9/20/2024 Mendel's Laws of Inheritance ▪ Mendel’s first law shows that alleles of genes have no permanent effect on one another when present in the same plant but segregate unchanged by passing into different gametes. ▪ Unlike the flower color of many types of plants, most blood group genes are inherited in a codominant manner. MENDEL’S LAW ▪ Experimented sweet pea flowers ▪ Parental: Bred all one color flower ▪ Homozygous for either red (RR) or white (rr) ▪ First Filial: Cross-bred two plants; obtained second generation ▪ Heterozygous (Rr) ▪ Second Filial: Produced red and white flowers in 3:1 ratio R r R RR Rr r Rr rr 6  9/20/2024 Mendel's Laws of Inheritance ▪ In codominance, both alleles are expressed, and their gene products are seen at the phenotypic level. ▪ In the MNSs blood group system, a heterozygous MN individual would type as both M and N antigen positive. Mendel's Laws of Inheritance ▪ Mendel’s second law is the law of independent assortment. ▪ Genes for different traits are inherited separately from each other. ▪ This allows for all possible combinations of genes to occur in the offspring. ▪ If the genes for separate traits are closely linked on a chromosome, they can be inherited together as a single unit (linkage). 7  9/20/2024 MENDEL’S LAW  Law of Independent Assortment  Example: Seeds - round and wrinkled and yellow and green  Parental genotypes RRYY and rryy ▪ R=Round; Y= Yellow; r=wrinkled; y=green)  Results are di-hybrid giving following phenotypes:  Round/yellow  Round/green  Wrinkled/yellow  Wrinkled/green  Ratio of 3:3:3:1 Hardy-Weinberg Principle ▪ This principle allows the study of Mendelian inheritance in great detail. ▪ The Hardy-Weinberg formula states (p + q)(p + q) = 1. ▪ p equals the gene frequency of the dominant allele ▪ q is the frequency of the recessive allele ▪ This can also be stated as: p2 + 2pq + q2= 1 ▪ This principle specifically addresses questions about recessive traits and how they can be persistent in populations. 8  9/20/2024 Let’s look at the following example of a population of pigs. Example If we know that the allele for a black coat is recessive. We can use the Hardy-Weinberg equation to determine the percent of the pig population that is heterozygous for white coat. 1. Calculate q2. Count the individuals that are homozygous recessive in the illustration above. Calculate the percent of the total population they represent. This is q2. Four of the sixteen individuals show the recessive phenotype, so the correct answer is 25% or 0.25. 2. Find q. Take the square root of q2 to obtain q, the frequency of the recessive allele. √0.25 = 0.5 3. Find p. The sum of the frequencies of both alleles = 100%, p + q = l. You know q, so what is p, the frequency of the dominant allele? P = 1 – 0.5 = 0.5 4. Find 2pq. The frequency of the heterozygotes is represented by 2pq. This gives you the percent of the population that is heterozygous for white coat. 2pq = 2(0.5) (0.5) = 0.5, so 50% of the population is heterozygous. Inheritance Patterns ▪ Inheritance patterns describe how a disease is transmitted in families. ▪ These patterns help to predict the recurrence risk for relatives. ▪ In general, inheritance patterns for single gene disorders are classified based on whether they are autosomal or X-linked and whether they have a dominant or recessive pattern of inheritance. 9  9/20/2024 Inheritance Patterns ▪ Autosomal Dominant Inheritance ▪ Mode of genetic inheritance by which only one copy of a disease allele is necessary for an individual to be susceptible to expressing the phenotype. ▪ Autosomal dominant inheritance is often called vertical inheritance because of the transmission from parent to offspring. Blue = Trait gene; Square Male; Circle = female ▪ Autosomal recessive ▪ In autosomal recessive inheritance, two copies of a disease allele are required for an individual to be susceptible to expressing the phenotype. ▪ Typically, the parents of an affected individual are not affected but are gene carriers. Blue/white = Trait gene; Square Male; Circle = female Inheritance Patterns ▪ X-linked dominant ▪ Only one copy of a disease allele on the X chromosome is required for an individual to be susceptible to an X-linked dominant disease. ▪ Both males and females can be affected, although males may be more severely affected because they only carry one Blue = X Trait gene; copy of genes found on the X chromosome. Square Male; Circle = female ▪ X-linked recessive inheritance ▪ Two copies of a disease allele on the X chromosome are required for an individual with two X chromosomes (female) to be affected with an X-linked recessive disease. ▪ Since males only have one X chromosome, any male with one copy of an X-linked recessive disease allele is affected. Blue dot & Blue = X Trait gene; Square Male; Circle = female 10  9/20/2024 Cellular Genetics ▪ Humans possess 46 chromosomes. ▪ 22 autosomes and 1 set of sex chromosomes ▪ Chromatin: nucleic acids and structural proteins called histones ▪ Heterochromatin: stains as dark bands ▪ Achromatin: stains as light bands; consists of highly condensed regions that are usually not transcriptionally active ▪ Euchromatin: swollen form of chromatin in cells, which is considered to be more active in the synthesis of RNA for transcription Cellular Genetics ▪ The specific location of a gene on a chromosome is called a locus (plural = loci). ▪ At each locus there may be only one, or several different forms of the gene, which are called alleles. ▪ Phenotype and genotype ▪ Homozygous and heterozygous ▪ The “silent” gene, or amorph ▪ Hemizygous refers to the condition when one chromosome has a copy of the gene and the other chromosome has that gene deleted or absent 11  9/20/2024 Cellular Genetics (5 of 5) ▪ Mitosis ▪ Meiosis Molecular Genetics ▪ Chromosomes are composed of long, linear strands of DNA tightly coiled around highly basic proteins called histones. 12  9/20/2024 Molecular Genetics: DNA ▪ DNA ▪ Purines and pyrimidines ▪ nitrogenous bases that make up the two different kinds of nucleotide bases in DNA and RNA. ▪ helical structure of DNA ▪ structure formed by double-stranded molecules of nucleic acids ▪ Codons and stop codons ▪ Codon-sequence of three nucleotides in the DNA strand for the genetic code for a specific amino acid ▪ Stop codon-sequence of three nucleotides that stop peptide from being translated form mRNA. Molecular Genetics: DNA Replication ▪ DNA Replication ▪ Photo reactivation (PR), excision repair (also referred to as cut and patch repair), recombinational repair, mismatch repair, and SOS repair 13  9/20/2024 Molecular Genetics: DNA Replication ▪ Factors Affecting DNA Replication ▪ Errors in the primary nucleotide sequence ▪ Chemical and environmental factors ▪ Ionizing radiation and strong oxidants ▪ Ultraviolet (UV) radiation ▪ Medications Molecular Genetics: DNA Repair ▪ DNA Repair Mechanisms ▪ Photo reactivation (PR) ▪ Excision repair (also referred to as cut and patch repair) ▪ Recombinational repair ▪ Mismatch repair ▪ SOS repair 14  9/20/2024 Molecular Genetics: DNA Mutations ▪ Mutations in DNA ▪ The original form of the DNA sequence, and the organism in which it occurs, is called the wild type. ▪ Mutations are any changes in the structure or sequence of DNA (physical of biochemical). ▪ The various chemicals and conditions that can cause mutations are referred to as mutagens. Molecular Genetics: RNA ▪ Ribonucleic Acid ▪ Ribosomal RNA (rRNA) ▪ Messenger RNA (mRNA) ▪ Transfer RNA (tRNA) ▪ Small RNA molecules which have other various functions within the cell 15  9/20/2024 Molecular Genetics: RNA ▪ Transcription is the cellular process by which one strand of duplex DNA is copied into RNA. Molecular Genetics: RNA ▪ Translation is the cellular process by which RNA transcripts are turned into proteins and peptides, the structural and functional molecules of the cell. ▪ Process involve three major steps ▪ Initiation ▪ Elongation ▪ Termination 16  9/20/2024 Molecular Genetics: RNA ▪ The translation process involve three major steps ▪ Initiation ▪ Elongation ▪ Termination ▪ After translation is complete, the mRNA is rapidly degraded by enzymes (a process that helps to control gene expression), or attaches to another ribosome, and the entire translation process starts all over again. ACCIDENTS CAN OCCUR MUTATION  A change in a gene potentially capable of being transmitted to offspring DELETION  The loss of a portion of chromosome INVERSION  The breaking of a chromosome during division, with subsequent reattachment occurring in an inverted or upside-down position. TRANSLOCATION  Transfer of a portion of one chromosome to its allele. 17  9/20/2024 Common Approaches in Modern Genetics Techniques ▪ Isolation of material ▪ Visualization ▪ Amplification ▪ Separation of species and subspecies ▪ Quantification The Role of Genetics in the Future ▪ DNA-based applicable to transfusion medicine. ▪ Genetic variation can impact response to many types of treatment. ▪ Personalized medicine ▪ Treatment and prevention of disease taking into account individual variability in genes, environment, and lifestyle for each person. 18  9/20/2024 Postamble ▪ READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES. ▪ USE THE UNIT OBJECTIVES AS A STUDY GUIDE ▪ All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives 19