Lec 9 Outline - Genetics - 2024

X-LINKAGE Genes that reside on the X-chromosome show very characteristic inheritance patterns in human pedigrees e.g. red-green colour blindness X-LINKED RECESSIVE MUTATION IN HUMANS  X-LINKED RECESSIVE...

X-LINKAGE Genes that reside on the X-chromosome show very characteristic inheritance patterns in human pedigrees e.g. red-green colour blindness X-LINKED RECESSIVE MUTATION IN HUMANS  X-LINKED RECESSIVE Unaffected male MUTATION IN Unaffected female HUMANS: Affected male Proven carrier female Hemophilia Possible carrier female Albert Victoria Edward VII George V Alexandra Nicholas II Wilhelm II Alfonso XIII Alexis GERMANY George VI RUSSIA Elizabeth II Philip Juan Carlos Diana Charles SPAIN Felipe Catherine William Henry BRITAIN GENETIC LINKAGE http://learn.genetics.utah.edu/content/pigeons/geneticlinkage/images/linkage- 1.jpg CROSSING OVER CREATES RECOMBINATION BETWEEN ALLELES OF A GENE  Crossing over between two genes results in two recombinant and two nonrecombinant chromosomes. The overall frequency of Nonrecombinant recombinant A B chromosomes is a A b Recombinant measure of a the genetic B Nonrecombinant distance a b between the two genes. CROSSING OVER MAY NOT OCCUR IN THE INTERVAL BETWEEN 2 LINKED GENES Genes that are linked have a recombination frequency between 0% - 50%. GENETIC MAPS MAPPING GENETIC RISK FACTORS  Y-LINKED GENES Only males exhibit the Females do not trait. inherit or transmit the trait. All sons of affected males are also affected. Y CHROMOSOME HAPLOTYPES  INHERITANCE OF MITOCHONDRIAL AND CHLOROPLAST DNA Mitochondria and chloroplast have their own genomes - code for enzymes that carry out the functions of that organelle - these genes move with the organelles during cell division - these genes are inherited independently from nuclear chromosomes INHERITANCE OF MITOCHONDRIAL DNA  INHERITANCE OF MITOCHONDRIAL DNA = MATERNAL INHERITANCE Only maternal mitochondria remain in the fertilized egg https://www.nature.com/articles/d41586-019-00093-1  https://www.nature.com/articles/d41586-019-00093-1 Individuals have a defect (nuclear gene mutation) that results in a mutant protein. This protein would be responsible for the accurate elimination of paternal mitochondrial DNA after fertilization.  The first step in genetic hypothesis testing is to understand the relationships between genotypes and phenotypes using symbols for alleles. Recessive mutations use the letter “R” or “r.” R represents the nonmutant allele. r represents the mutant allele. Autosomal recessive traits have X-linked recessive traits have the the following KEY relating following KEY relating genotype genotype and phenotype. and phenotype. Females Males genotype phenotype genotype phenotype genotype phenotype RR unaffected RR unaffected RY unaffected Rr unaffected Rr unaffected rY affected rr affected rr affected Dominant mutations use the letter “D” or “d.” D represents the mutant allele. d represents the nonmutant allele. Autosomal dominant traits have X-linked dominant traits have the following KEY relating the following KEY relating genotype and phenotype. genotype and phenotype. Females Males genotype phenotype genotype phenotype genotype phenotype DD affected DD affected DY affected Dd affected Dd affected dY unaffected dd unaffected dd unaffected  GENOMES, MUTATION AND GENETIC VARIATION Relevant reading: Morris, 4th edition, Chapters 12 &13  GENOMES A genome is the genetic material of a cell, organism, organelle, or virus, and its sequence is the order of bases along the DNA or (in some viruses) RNA. A genome is the genetic material transmitted from parents to offspring. The number of genes in a genome and the size of a genome do not correlate well with the complexity of an organism. GENOME SIZE https://primitivefishes.files.wordpress.com/2012/05/pf-mal- 1.jpg GENOME SIZE C-value paradox = contradiction between genome size and organismal complexity  GENE NUMBERS Gene number is not a good predictor of biological complexity.  SEQUENCE The human genome also contains several types COMPOSITION of sequences called transposons. This DNA can replicate and insert itself into OF THE HUMAN new positions in the genome. DNA transposons: replicate and transpose via GENOME DNA replication and repair. Retrotranposons: transpose by means of an RNA intermediate.  MUTATION Variation in different individuals’ genomes happen due to mutation Mutation = any heritable change in the genetic material Generally, mutations tend to occur spontaneously and at random Mutations can take place in reproductive cells = germ-line mutations; or in non-reproductive cells = somatic mutations  SOMATIC MUTATIONS VERSUS GERMLINE MUTATIONS: CANCER  The sterile velvet template picks up both By chance, mutant and this colony nonmutant contains a cells. few mutant Nonselective cells. medium Incubation to allow growth of colonies Only the mutant cells grow on selective medium; the position of the Selective medium colony tells you which colony on the nonselective medium contains the mutant cells. HOW DO MUTATIONS ARISE?  HOW DID THE MUTATIONS ARISE? Had the mutation arisen spontaneously in the bacteria and was already present prior to plating on selection media? -mutations arise without regard for the needs of the organism Did the mutation arise after and in response to being plated on the selection media? -the needs of the organism do have some type of impact on the process of mutation  HOW DO The sterile MUTATIONS ARISE? velvet template picks up both By chance, mutant and this colony nonmutant contains a cells. few mutant Nonselective cells. Incubation to allow medium growth of colonies Mutant colony identified on Only the mutant original plate cells grow on selective medium; the position of the Selective medium colony tells you which colony on the Culture diluted nonselective Nonselective and cells spread medium contains medium on selective the mutant cells. medium Pure culture of antibiotic-resistant bacteria  HOW DID THE MUTATIONS ARISE? Had the mutation arisen spontaneously in the bacteria and was already present prior to plating on selection media? -mutations arise without regard for the needs of the organism Did the mutation arise after and in response to being plated on the selection media? -the needs of the organism do have some type of impact on the process of mutation Chapter 13 Active Lecture Slide 59 How do mutations occur? Can be caused by hydrogen Can be caused by X- peroxide Can be caused Can be caused Can be caused by radiation rays by UV light by highly reactive chemicals Many different types of mutations are spontaneous and caused by mutagens. POINT MUTATIONS – CHNAGES IN A SINGLE NUCLEOTIDE  DO POINT MUTATIONS MATTER? a. Nonmutant b. Synonymous c. Nonsynonymous mutation mutation DNA Transcribed Transcription strand mRNA Translation Protein The nonmutant A nucleotide substitution A nucleotide substitution gene expresses that does not change the that changes the amino acid normal b-globin. amino acid is a synonymous is a nonsynonymous mutation (silent mutation). mutation (missense mutation).  SICKLE-CELL ANEMIA c. Nonsynonymous Mutation in β-globin gene DNA mRNA Protein A nucleotide substitution that changes the amino acid is a nonsynonymous mutation (missense mutation). http://learn.genetics.utah.edu/content/disorders/singlegene/sicklecell/images/sicklecell.jpg  NONSENSE MUTATIONS a. Nonmutant b. Nonsense mutation DNA Transcribed Transcription strand mRNA Translation STOP Protein A nucleotide substitution that creates a stop codon is called a nonsense mutation.  INSERTIONS AND DELETIONS a. Nonmutant b. Mutant DNA Transcription Transcribed strand mRNA Translation Protein Missing amino acid (PHE)  Nonmutant DNA Transcription Transcribed strand mRNA Translation FRAMESHIFT Protein MUTATIONS Frameshift mutation (insertion) DNA Transcription mRNA Translation Protein An insertion or deletion that is not an exact multiple of three nucleotides changes the reading frame of translation. Such a mutation is called a frameshift mutation.  GENETIC VARIATION: WE ARE ALL MUTANTS! Genetic variation: genetic differences that exist among individuals in a population at a particular point in time Genetic variation = variety of different genotypes = variety of different phenotypes  GENETIC VARIATION: POLYMORPHISMS Mutation is the ultimate source of variation in genotypes Common genetic differences that exist between individuals = polymorphisms - differences are typically seen at single nucleotides = single nucleotide polymorphisms (SNPs) http://learn.genetics.utah.edu/content/precision/snips/images/snp-quick-ref.jpg GENOTYPE-BY-ENVIRONMENT INTERACTIONS WT Sickle cell anemia Most genetic variation in populations occurs in non-coding DNA (rather than in genes) = direct studies of DNA reveal such differences Most genetic variation is neutral -- no obvious effects  Position of PCR Allele A1 primers Allele A2 VARIABLE NUMBER OF TANDEM Allele A3 REPEATS (VNTR) Allele A4 Different individuals may have different numbers of repeated sequences in particular locations on Allele A5 their chromosomes VNTR = DNA FINGERPRINTING Evidence (blood or other tissue from a crime scene) Genotype Each of the different genotypes yields a unique pattern of bands in the gel. THE GENETIC AND ENVIRONMENTAL BASIS OF COMPLEX TRAITS Relevant reading: Morris, 4th edition, Chapter 16 COMPLEX TRAITS Complex traits such as height and blood pressure are called quantitative traits = measure along a continuum with only small intervals between similar individuals. COMPLEX TRAITS INFLUENCED BY THE ENVIRONMENT Environmental factors can affect the variation in phenotype between individuals (e.g., amount of sunlight, water, wind, nutrients). Environmental risk factors exist for several common human diseases e.g., high salt intake for high blood pressure  COMPLEX TRAITS INFLUENCED BY MULTIPLE GENES Two plants heterozygous for each of three unlinked genes affecting the color of seed casing are crossed. Aa Bb Cc ´ Aa Bb Cc The genes act cumulatively to determine the intensity of red coloration; in this example, each upper-case allele in the genotype adds more red to the phenotype. ABC abc ABc 3 abC AbC aBc Female aBC 2 4 Abc Male 2 3 4 gametes Abc 2 3 3 4 aBC gametes aBc 1 3 3 3 5 AbC abC 1 2 3 4 5 ABc 3 abc 1 2 2 5 ABC 3 4 4 0 2 2 2 4 4 4 6 1 2 2 3 4 4 5 1 2 3 3 4 5 1 3 3 3 5 2 3 3 4 2 3 4 2 4 3 COMPLEX TRAITS INFLUENCED BY MULTIPLE GENES